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1.
Sci Rep ; 10(1): 12110, 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32694637

RESUMO

We evaluated the diagnostic performance and generalizability of traditional machine learning and deep learning models for distinguishing glioblastoma from single brain metastasis using radiomics. The training and external validation cohorts comprised 166 (109 glioblastomas and 57 metastases) and 82 (50 glioblastomas and 32 metastases) patients, respectively. Two-hundred-and-sixty-five radiomic features were extracted from semiautomatically segmented regions on contrast-enhancing and peritumoral T2 hyperintense masks and used as input data. For each of a deep neural network (DNN) and seven traditional machine learning classifiers combined with one of five feature selection methods, hyperparameters were optimized through tenfold cross-validation in the training cohort. The diagnostic performance of the optimized models and two neuroradiologists was tested in the validation cohort for distinguishing glioblastoma from metastasis. In the external validation, DNN showed the highest diagnostic performance, with an area under receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy of 0.956 (95% confidence interval [CI], 0.918-0.990), 90.6% (95% CI, 80.5-100), 88.0% (95% CI, 79.0-97.0), and 89.0% (95% CI, 82.3-95.8), respectively, compared to the best-performing traditional machine learning model (adaptive boosting combined with tree-based feature selection; AUC, 0.890 (95% CI, 0.823-0.947)) and human readers (AUC, 0.774 [95% CI, 0.685-0.852] and 0.904 [95% CI, 0.852-0.951]). The results demonstrated deep learning using radiomic features can be useful for distinguishing glioblastoma from metastasis with good generalizability.

3.
Molecules ; 25(12)2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32630467

RESUMO

In this study, we investigated the tumor targeting effect in cancer cells using triphenylphosphonium (TPP) cations, which are accumulated by differences in membrane potential, and folic acid (FA), which is selectively bound to overexpressed receptors on various cancer cells. We used Food and Drug Administration (FDA)-approved silica nanoparticles (SNPs) as drug carriers, and SNPs conjugated with TPP and FA (STFs) samples were prepared by introducing different amounts of TPP and FA onto the nanoparticle surfaces. STF-1, 2, 3, 4 and 5 are named according to the combination ratio of TPP and FA on the particle surface. To confirm the tumor targeting effect, 89Zr (t1/2 = 3.3 days) was coordinated directly to the silanol group of SNP surfaces without chelators. It was shown that the radiochemical yield was 69% and radiochemical purity was >99%. In the cellular uptake evaluation, SNPs with the most TPP (SFT-5) and FA (SFT-1) attached indicated similar uptake tendencies for mouse colon cancer cells (CT-26). However, the results of the cell internalization assay and measurement of positron emission tomography (PET) images showed that SFT-5 had more affinity for the CT-26 tumor than other samples the TPP ratio of which was lower. Consequently, we confirmed that TPP ligands affect target cancer cells more than FA, which means that cell membrane potential is significantly effective for tumor targeting.

4.
Medicine (Baltimore) ; 99(27): e21017, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629723

RESUMO

INTRODUCTION: Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is an alternative treatment option for patients with acute cholecystitis, especially for those who are unsuitable for cholecystectomy. Recently used luminal apposing metal stents (LAMS) in EUS-GBD has several advantages over standard metal stents. However, there is no current guideline on where to locate the LAMS when transgastric approach is required. This study reports a case of gastric outlet obstruction (GOO) by placing LAMS too close to the pyloric ring. PATIENT CONCERNS: A 79-year-old female patient was referred to our department for evaluation of a large hepatic mass on abdominal ultrasound. Abdominal pain on right upper quadrant and spiking fever up to 38 °C appeared after liver biopsy. Abdominal ultrasound showed thickened GB wall and positive sonographic Murphy sign. DIAGNOSES: Intrahepatic cholangiocarcinoma with multiple lung and intrahepatic metastasis, acute cholecystitis, and pyloric ring obstruction caused by flange of LAMS in EUS-GBD. INTERVENTIONS: EUS-GBD via transgastric approach was performed with LAMS. After complete deployment of stent, esophagogastroduodenoscopy showed complete GOO by flange of LAMS. A gastroduodenal metal stent was inserted to relieve the GOO. OUTCOMES: The patient recovered well. She did not complain about obstruction induced symptom such as vomiting or abdominal fullness after gastroduodenal stent insertion. CONCLUSION: To the best of our knowledge, this is the first case report of EUS-GBD induced GOO. If physicians use LAMS as a transgastric approach in EUS-GBD, the puncture site should be carefully selected considering the size of the flange.


Assuntos
Colangiocarcinoma/complicações , Obstrução da Saída Gástrica/etiologia , Neoplasias Hepáticas/diagnóstico por imagem , Stents/efeitos adversos , Idoso , Colecistite Aguda/etiologia , Drenagem/métodos , Endossonografia/métodos , Feminino , Vesícula Biliar/diagnóstico por imagem , Vesícula Biliar/patologia , Obstrução da Saída Gástrica/cirurgia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Resultado do Tratamento , Ultrassonografia/métodos , Ultrassonografia de Intervenção/instrumentação
5.
PLoS One ; 15(6): e0233791, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584909

RESUMO

BACKGROUND: Machine learning (ML) is able to extract patterns and develop algorithms to construct data-driven models. We use ML models to gain insight into the relative importance of variables to predict obstructive coronary artery disease (CAD) using the Coronary Computed Tomographic Angiography for Selective Cardiac Catheterization (CONSERVE) study, as well as to compare prediction of obstructive CAD to the CAD consortium clinical score (CAD2). We further perform ML analysis to gain insight into the role of imaging and clinical variables for revascularization. METHODS: For prediction of obstructive CAD, the entire ICA arm of the study, comprising 719 patients was used. For revascularization, 1,028 patients were randomized to invasive coronary angiography (ICA) or coronary computed tomographic angiography (CCTA). Data was randomly split into 80% training 20% test sets for building and validation. Models used extreme gradient boosting (XGBoost). RESULTS: Mean age was 60.6 ± 11.5 years and 64.3% were female. For the prediction of obstructive CAD, the AUC was significantly higher for ML at 0.779 (95% CI: 0.672-0.886) than for CAD2 (0.696 [95% CI: 0.594-0.798]) (P = 0.01). BMI, age, and angina severity were the most important variables. For revascularization, the model obtained an overall area under the receiver-operation curve (AUC) of 0.958 (95% CI = 0.933-0.983). Performance did not differ whether the imaging parameters used were from ICA (AUC 0.947, 95% CI = 0.903-0.990) or CCTA (AUC 0.941, 95% CI = 0.895-0.988) (P = 0.90). The ML model obtained sensitivity and specificity of 89.2% and 92.9%, respectively. Number of vessels with ≥70% stenosis, maximum segment stenosis severity (SSS) and body mass index (BMI) were the most important variables. Exclusion of imaging variables resulted in performance deterioration, with an AUC of 0.705 (95% CI 0.614-0.795) (P <0.0001). CONCLUSIONS: For obstructive CAD, the ML model outperformed CAD2. BMI is an important variable, although currently not included in most scores. In this ML model, imaging variables were most associated with revascularization. Imaging modality did not influence model performance. Removal of imaging variables reduced model performance.

6.
Chest ; 158(2): 739-750, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32298733

RESUMO

BACKGROUND: Heart failure (HF) is a leading cause of morbidity and mortality and although it is linked to sleep apnea, which physiological stressors most strongly associate with incident disease is unclear. We tested whether sleep apnea-specific hypoxic burden (SASHB) predicts incident HF in two independent cohort studies. RESEARCH QUESTION: In comparison with apnea-hypopnea index (AHI), how does sleep apnea-specific hypoxic burden predict incident HF? STUDY DESIGN AND METHODS: The samples were derived from two cohort studies: The Sleep Heart Health Study (SHHS), which included 4,881 middle-aged and older adults (54.4% women), age 63.6 ± 11.1 years; and the Outcomes of Sleep Disorders in Older Men (MrOS), which included 2,653 men, age 76.2 ± 5.4 years. We computed SASHB as the sleep apnea-specific area under the desaturation curve from pre-event baseline. We used Cox models for incident HF to estimate the adjusted hazard ratios (HRs) for natural log-transformed SASHB and AHI adjusting for multiple confounders. RESULTS: The SASHB predicted incident HF in men in both cohorts, whereas AHI did not. Men in SHHS and MrOS had adjusted HRs (per 1SD increase in SASHB) of 1.18 (95% CI, 1.02-1.37) and 1.22 (95% CI, 1.02-1.45), respectively. Associations with SASHB were observed in men with both low and high AHI levels. Associations were not significant in women. INTERPRETATION: In men, the hypoxic burden of sleep apnea was associated with incident HF after accounting for demographic factors, smoking, and co-morbidities. The findings Suggest that quantification of an easily measured index of sleep apnea-related hypoxias may be useful for identifying individuals at risk for heart disease, while also suggesting targets for intervention.

7.
Trials ; 21(1): 353, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32321551

RESUMO

BACKGROUND: Despite the chronicled success of low-density lipoprotein cholesterol (LDLc)-lowering statin therapy, substantial residual cardiovascular (CV) disease risk remains a problem worldwide, highlighting the need to for combination therapies targeting non-LDLc factors, such as with fenofibrate. METHODS/DESIGN: The STAFENO trial is a prospective, randomized, open-label, multi-center trial to compare the effect of statin plus fenofibrate with statin alone on the reduction and stabilization of plaque in non-diabetic, combined dyslipidemia patients with non-intervened, intermediate coronary artery disease (CAD) using virtual histology-intravascular ultrasound at 12 months. A total of 106 eligible patients are planned to be randomized to receive either a combination therapy (rosuvastatin 10 mg plus fenofibrate 160 mg/day) or monotherapy (rosuvastatin 10 mg/day) for 12 months. The primary endpoint of this study is the percentage change in the necrotic core volume. Secondary endpoints include changes in tissue characteristics and 1-year major CV events, including all-cause mortality, CV mortality, nonfatal myocardial infarction, stroke, and revascularization of the intervened and non-intervened lesions. DISCUSSION: The STAFENO trial will address whether combination treatment of statin and fenofibrate has an additive beneficial effect compared to statin alone on the reduction and stabilization of plaque and CV events in non-diabetic, combined dyslipidemia patients with non-intervened intermediate CAD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02232360. Registered 9 February 2014. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0004ULE&selectaction=Edit&uid=U00023SZ&ts=2&cx=juppd2.

8.
Korean J Gastroenterol ; 75(4): 198-206, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32326686

RESUMO

Background/Aims: With recent changes in the treatment of pancreatic cancer, patients' active decision-making has become more important. Nevertheless, it is difficult to give patients proper insights into the disease. The purpose of this study was to determine associated factors between pancreatic cancer awareness and treatment decisions as well as how cancer awareness affects the timing of treatment decisions and the desired treatment method. Methods: This is a retrospective study that reviewed and analyzed the electronic medical records of 110 patients who were diagnosed with pancreatic cancer from January 2013 to April 2016. A "patient with pancreatic cancer awareness" means that the patient was informed of their disease state before making the first treatment decision. Results: Of all, only 63.6% of patients (n=70) were shown to have pancreatic cancer awareness before making their first treatment decision. Compared to patients without pancreatic cancer awareness, patients with pancreatic cancer awareness were younger (65.00 vs. 76.98, t=6.70, p<0.001), were more likely to have presented their spouse as legal guardians (42.9% vs. 10.0%, χ2=31.70, p<0.001), and spent a shorter time for treatment decision-making (1.6 vs. 10.5 days, t=4.26, p<0.001). The patients without pancreatic cancer awareness were more likely to opt for best supportive care compared to the patients with pancreatic cancer awareness (79.5% vs. 28.6%, χ2=31.70, p<0.001). Conclusions: This study provides insights into cancer awareness. Since cancer awareness appears to influence treatment decision, it is necessary to develop guidelines to improve cancer awareness of patients.

9.
Eur Arch Otorhinolaryngol ; 277(7): 1969-1975, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32170420

RESUMO

PURPOSE: Epistaxis that is refractory to conservative management can be treated with endoscopic sphenopalatine artery ligation (ESPAL). Although rare, ethmoidal artery (EA) bleeding can be a cause of rebleeding after successful ESPAL. EA bleeding is diagnosed by angiography and can also be identified during surgical exploration. However, since the angiographic embolization of the EA is contraindicated, surgical hemostasis is mandatory. This study investigated whether paranasal sinus (PNS) CT could provide information for predicting EA bleeding without angiography in patients with refractory epistaxis requiring ESPAL. METHODS: Forty-seven patients, who were surgically treated [with ESPAL or EA ligation (EAL)] for refractory epistaxis from March 2010 to June 2019, were retrospectively analyzed. A positive PNS CT finding for EA bleeding was defined as the presence of soft tissue densities having continuity with the EA pathway, accompanied by a partially deficient surrounding bony canal. These findings as well as soft tissue densities in each paranasal sinus were compared between the ESPAL and EAL groups. RESULTS: All patients in the EAL group had positive CT findings of EA bleeding, compared to only 12.2% in the ESPAL group (P < 0.001). The rate of soft tissue densities within the frontal and sphenoid sinuses were noted in 26.8% and 17.1% of patients in the ESPAL group, compared to 83.3% and 83.3% of patients in the EAL group (P = 0.013 and P = 0.003, respectively). CONCLUSION: PNS CT might be useful for predicting EA bleeding in patients with refractory epistaxis requiring surgical hemostasis.

10.
Endocrinol Metab (Seoul) ; 35(1): 188-191, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32207279

RESUMO

X-linked adrenoleukodystrophy (X-ALD) occurs due to mutations in the ABCD1 gene that encodes the peroxisomal membrane protein peroxisomal transporter ATP-binding cassette sub-family D member 1 (ABCD1). Degradation of very long-chain fatty acids in peroxisomes is impaired owing to ABCD dysfunction, subsequently leading to adrenomyeloneuropathy, cerebral adrenoleukodystrophy, and adrenal insufficiency. X-ALD frequently induces idiopathic Addison's disease in young male patients. Here, we confirmed the diagnosis of X-ALD in a young male patient with primary adrenal insufficiency, and identified a novel ABCD1 gene mutation (p.Trp664*, c.1991 G>A).

12.
Sci Rep ; 10(1): 1637, 2020 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005929

RESUMO

Characterizing upper airway occlusion during natural sleep could be instrumental for studying the dynamics of sleep apnea and designing an individualized treatment plan. In recent years, obstructive sleep apnea (OSA) phenotyping has gained attention to classify OSA patients into relevant therapeutic categories. Electrical impedance tomography (EIT) has been lately suggested as a technique for noninvasive continuous monitoring of the upper airway during natural sleep. In this paper, we developed the automatic data processing and feature extract methods to handle acquired EIT data for several hours. Removing ventilation and blood flow artifacts, EIT images were reconstructed to visualize how the upper airway collapsed and reopened during the respiratory event. From the time series of reconstructed EIT images, we extracted the upper airway closure signal providing quantitative information about how much the upper airway was closed during collapse and reopening. Features of the upper airway dynamics were defined from the extracted upper airway closure signal and statistical analyses of ten OSA patients' data were conducted. The results showed the feasibility of the new method to describe the upper airway dynamics during sleep apnea, which could be a new step towards OSA phenotyping and treatment planning.

13.
Sleep ; 43(7)2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32043131

RESUMO

STUDY OBJECTIVES: Oral appliance therapy is an increasingly common option for treating obstructive sleep apnea (OSA) in patients who are intolerant to continuous positive airway pressure (CPAP). Clinically applicable tools to identify patients who could respond to oral appliance therapy are limited. METHODS: Data from three studies (N = 81) were compiled, which included two sleep study nights, on and off oral appliance treatment. Along with clinical variables, airflow features were computed that included the average drop in airflow during respiratory events (event depth) and flow shape features, which, from previous work, indicates the mechanism of pharyngeal collapse. A model was developed to predict oral appliance treatment response (>50% reduction in apnea-hypopnea index [AHI] from baseline plus a treatment AHI <10 events/h). Model performance was quantified using (1) accuracy and (2) the difference in oral appliance treatment efficacy (percent reduction in AHI) and treatment AHI between predicted responders and nonresponders. RESULTS: In addition to age and body mass index (BMI), event depth and expiratory "pinching" (validated to reflect palatal prolapse) were the airflow features selected by the model. Nonresponders had deeper events, "pinched" expiratory flow shape (i.e. associated with palatal collapse), were older, and had a higher BMI. Prediction accuracy was 74% and treatment AHI was lower in predicted responders compared to nonresponders by a clinically meaningful margin (8.0 [5.1 to 11.6] vs. 20.0 [12.2 to 29.5] events/h, p < 0.001). CONCLUSIONS: A model developed with airflow features calculated from routine polysomnography, combined with age and BMI, identified oral appliance treatment responders from nonresponders. This research represents an important application of phenotyping to identify alternative treatments for personalized OSA management.

14.
Int J Pediatr Otorhinolaryngol ; 132: 109903, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-32014737

RESUMO

BACKGROUND: We introduced a surgical procedure which includes a simple sinusectomy without opening the sinus whilst attempting to minimize the skin incision. METHODS: A total of 34 patients with preauricular sinus were treated. In six patients, this technique was performed bilaterally, so a total of 40 ears were enrolled and analyzed for recurrence rate and surgical outcome in retrospective observational study. A database was created which included patient age, the preoperative and postoperative incision size, suture materials used, and complications. Incisional size according to the previous infection condition and incision and drainage (I & D) history were analyzed. RESULTS: The mean initial skin incision length was 0.75 ± 0.40 cm and mean incision length after skin suture was 0.81 ± 0.42 cm. The young group under 10 years of age had a mean initial skin incision length of 0.56 ± 0.06 cm, and mean incision length after skin suture was 0.58 ± 0.08 cm. Suture materials were Nylon 6-0 for 14 ears, Nylon 7-0 for 20 ears, and Nylon 8-0 for 6 ears. The incidence of minor complications (immediate wound dehiscence, wound opening at a previous I & D region, keloid formation) was 7.5%. CONCLUSION: Our method overcomes potential problems with esthetics in addition to reducing the recurrence rates of preauricular sinusectomy. With our technique, minimization of skin incision length is possible without the risk of recurrence. The use of fine suture materials and not using drainage avoids additional skin trauma.

15.
Clin Endosc ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31906606

RESUMO

Advanced colorectal cancer can cause acute colonic obstruction, which is a life-threatening condition that requires emergency bowel decompression. Malignant colonic obstruction has traditionally been treated using emergency surgery, including primary resection or stoma formation. However, relatively high rates of complications, such as anastomosis site leakage, have been considered as major concerns for emergency surgery. Endoscopic management of malignant colonic obstruction using a self-expandable metal stent (SEMS) was introduced 20 years ago and because of its application as a palliative management tool, there is sufficient evidence for its application as first-line treatment. However, endoscopic treatment of malignant colonic obstruction using SEMSs as a bridge to surgery remains controversial owing to short-term complications and long-term oncological outcomes. In this review, the current status of and recommendations for endoscopic management using SEMSs for malignant colonic obstruction will be discussed.

16.
J Allergy Clin Immunol ; 145(5): 1378-1388.e10, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31987845

RESUMO

BACKGROUND: Staphylococcus aureus enterotoxin (SAE) superantigens are detected in nasal polyps (NPs), and SAE-specific IgE predicts asthma comorbidity in patients with NPs. However, roles of SAE superantigens and superantigen-related T-cell responses remain to be elucidated in nonasthmatic patients. OBJECTIVE: We investigated the presence of SAEs and SAE-related T-cell receptor (TCR) Vß (TCRVß) in nonasthmatic NPs, the phenotypes and functions of SAE-related T cells, and the clinical implication of SAE-related T-cell expansion. METHODS: Sinonasal tissue samples were obtained from patients with nonasthmatic chronic rhinosinusitis (CRS) with NPs (CRSwNP), patients with CRS without NPs (CRSsNP), and control subjects. SAE genes were detected by PCR, and the TCRVß distribution and T-cell phenotypes were examined by flow cytometry. RESULTS: Various SAE genes were detected not only in NPs but also in sinonasal mucosa from patients with CRSsNP and from controls. The S aureus enterotoxin I (SEI) gene was detected in all NPs. The fraction of SEI-responsive TCRVß+ (TCRVß1+ and Vß5.1+) CD4+ T cells was significantly increased only in NPs and the ethmoidal mucosa of patients with CRSwNP, indicating superantigen-induced expansion. The expanded TCRVß5.1+ CD4+ T cells expressed proliferation marker Ki-67 and the TH2 transcription factor GATA3. Furthermore, TCRVß5.1+ CD4+ T cells in NPs highly expressed TH2 markers, including IL-17RB, thymic stromal lymphoprotein receptor, and chemoattractant receptor-homologous molecule expressed on TH2 cells, with a potent TH2 cytokine-producing ability. Moreover, the expansion of TCRVß1+ or Vß5.1+ CD4+ T cells was associated with the Lund-Mackay computed tomography score, indicating disease extent. CONCLUSION: In nonasthmatic patients with CRSwNP, superantigen-related expansion of CD4+ T cells with TH2 differentiation was associated with the disease extent.

17.
J Gastroenterol Hepatol ; 35(5): 760-768, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31498502

RESUMO

BACKGROUND AND AIM: We conducted a nationwide validation study of diagnostic algorithms to identify cases of inflammatory bowel disease (IBD) within the Korea National Health Insurance System (NHIS) database. METHOD: Using the NHIS dataset, we developed 44 algorithms combining the International Classification of Diseases (ICD)-10 codes, codes for Rare and Intractable Diseases (RID) registration and claims data for health care encounters, and pharmaceutical prescriptions for IBD-specific drugs. For each algorithm, we compared the case identification results from electronic medical records data with the gold standard (chart-based diagnosis). A multiple sampling test verified the validation results from the entire study population. RESULTS: A random nationwide sample of 1697 patients (848 potential cases and 849 negative control cases) from 17 hospitals were included for validation. A combination of the ICD-10 code, ≥ 1 claims for health care encounters, and ≥ 1 prescription claims (reference algorithm) achieved excellent performance (sensitivity, 93.1% [95% confidence interval 91-94.7]; specificity, 98.1% [96.9-98.8]; positive predictive value, 97.5% [96.1-98.5]; negative predictive value, 94.5% [92.8-95.8]) with the lowest error rate (4.2% [3.3-5.3]). The multiple sampling test confirmed that the reference algorithm achieves the best performance regarding IBD diagnosis. Algorithms including the RID registration codes exhibited poorer performance compared with that of the reference algorithm, particularly for the diagnosis of patients affiliated with secondary hospitals. The performance of the reference algorithm showed no statistical difference depending on the hospital volume or IBD type, with P-value < 0.05. CONCLUSIONS: We strongly recommend the reference algorithm as a uniform standard operational definition for future studies using the NHIS database.

19.
Gut Liver ; 13(5): 531-540, 2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-31505907

RESUMO

Background/Aims: This nationwide, multicenter prospective randomized controlled trial aimed to compare the efficacy and safety of 10-day concomitant therapy (CT) and 10-day sequential therapy (ST) with 7-day clarithromycin-containing triple therapy (TT) as first-line treatment for Helicobacter pylori infection in the Korean population. Methods: Patients with H. pylori infection were assigned randomly to 7d-TT (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for 7 days), 10d-ST (lansoprazole 30 mg and amoxicillin 1 g twice daily for the first 5 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg twice daily for the remaining 5 days), or 10d-CT (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 10 days). The primary endpoint was eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. Results: A total of 1,141 patients were included. The 10d-CT protocol achieved a markedly higher eradication rate than the 7d-TT protocol in both the ITT (81.2% vs 63.9%) and PP analyses (90.6% vs 71.4%). The eradication rate of the 10d-ST protocol was superior to that of the 7d-TT protocol (76.3% vs 63.9%, ITT analysis; 85.0% vs 71.4%, PP analysis). No significant differences in adherence or serious side effects were found among the three treatment arms. Conclusions: The 10d-CT and 10d-ST regimens were superior to the 7d-TT regimen as standard first-line treatment in Korea.


Assuntos
Antibacterianos/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Inibidores da Bomba de Prótons/administração & dosagem , Amoxicilina/administração & dosagem , Claritromicina/administração & dosagem , Erradicação de Doenças/métodos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Infecções por Helicobacter/prevenção & controle , Humanos , Lansoprazol/administração & dosagem , Masculino , Adesão à Medicação , Metronidazol/administração & dosagem , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia , Resultado do Tratamento
20.
Intest Res ; 17(4): 527-536, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31426622

RESUMO

BACKGROUND/AIMS: Transforming growth factor-ß1 (TGF-ß1) induction of epithelial-mesenchymal transition (EMT) is one of the mechanisms by which colorectal cancer (CRC) cells acquire migratory and invasive capacities, and subsequently metastasize. Parthenolide (PT) expresses multiple anti-cancer and anti-inflammatory activities that inhibit nuclear factor κB by targeting the IκB kinase complex. In the present study, we aimed to investigate whether PT can inhibit TGF-ß1-induced EMT in CRC cell lines. METHODS: HT-29 and SW480 cell lines were used in the experiment. Cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and sub-G1 analysis was measured by flow cytometry. The induction of EMT by TGF-ß1 and inhibition of the process by PT was analyzed by phase contrast microscopy, wounding healing, cellular migration and invasion assays, and Western blotting. RESULTS: TGF-ß1 inhibits HT-29 cell proliferation, but has no effect on SW480 cell proliferation; different concentrations of TGF-ß1 did not induce apoptosis in HT-29 and SW480 cells. PT attenuates TGF-ß1-induced elongated, fibroblast-like shape changing in cells. PT inhibits TGF-ß1-induced cell migration and cell invasion. In addition, other EMT markers such as ß-catenin, Vimentin, Snail, and Slug were suppressed by PT, while E-cadherin was increased by PT. CONCLUSIONS: Our findings show that PT inhibits TGF-ß1-induced EMT by suppressing the expression of the mesenchymal protein and increasing expression of the epithelial protein. These findings suggest a novel approach for CRC treatment by suppression of TGF-ß1-induced EMT.

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