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1.
Dig Dis Sci ; 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38949750

ABSTRACT

BACKGROUND: There are scanty population-based studies investigating the incidence and prevalence rates of inflammatory bowel disease (IBD) in Taiwan. AIMS: This study aimed to estimate the nationwide prevalence and incidence of IBD and identify its noticeable trends in Taiwan between 2016 and 2020. METHODS: A retrospective study by analyzing the data from the National Health Insurance Research Database of Taiwan. RESULTS: A total of 2595 patients with catastrophic IBD illness were registered from 2016 to 2020 in Taiwan (CD, 880; UC, 1715). The male-to-female ratio in the study sample was 1.83:1 for CD and 1.69:1 for UC. The median age of those registered with CD and UC was 37 and 47 years, respectively. The incidence rate of CD was 0.65 per 100,000 persons in 2016 and it was increased to 0.81 per 100,000 persons in 2020. The incidence rate of UC was 1.16 per 100,000 persons in 2016 and it was increased to 1.53 in 2020. Overall, the incidence of IBD was increase from 1.81 per 100,000 persons to 2.34 per 100,000 persons between 2016 and 2020. Overall, the prevalence rates of IBD was increase from 14.95 per 100,000 persons to 20.02 per 100,000 persons between 2016 and 2020. CONCLUSION: The epidemiological stages of IBD in Taiwan was considered in the acceleration in incidence stage, during which incidence rises and prevalence is relatively low. Understanding these geographical differences is important for the rising global burden of IBD.

2.
J Gastroenterol Hepatol ; 39(4): 733-739, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38225761

ABSTRACT

BACKGROUND AND AIM: Colonoscopy is a useful method for the diagnosis and management of colorectal diseases. Many computer-aided systems have been developed to assist clinicians in detecting colorectal lesions by analyzing colonoscopy images. However, fisheye-lens distortion and light reflection in colonoscopy images can substantially affect the clarity of these images and their utility in detecting polyps. This study proposed a two-stage deep-learning model to correct distortion and reflections in colonoscopy images and thus facilitate polyp detection. METHODS: Images were collected from the PolypSet dataset, the Kvasir-SEG dataset, and one medical center's patient archiving and communication system. The training, validation, and testing datasets comprised 808, 202, and 1100 images, respectively. The first stage involved the correction of fisheye-related distortion in colonoscopy images and polyp detection, which was performed using a convolutional neural network. The second stage involved the use of generative and adversarial networks for correcting reflective colonoscopy images before the convolutional neural network was used for polyp detection. RESULTS: The model had higher accuracy when it was validated using corrected images than when it was validated using uncorrected images (96.8% vs 90.8%, P < 0.001). The model's accuracy in detecting polyps in the Kvasir-SEG dataset reached 96%, and the area under the receiver operating characteristic curve was 0.94. CONCLUSION: The proposed model can facilitate the clinical diagnosis of colorectal polyps and improve the quality of colonoscopy.


Subject(s)
Colonic Polyps , Colorectal Neoplasms , Deep Learning , Humans , Colonic Polyps/diagnostic imaging , Colonic Polyps/pathology , Colonoscopy/methods , Neural Networks, Computer , Colorectal Neoplasms/pathology
3.
Sensors (Basel) ; 23(3)2023 Jan 20.
Article in English | MEDLINE | ID: mdl-36772251

ABSTRACT

Colonoscopy is a valuable tool for preventing and reducing the incidence and mortality of colorectal cancer. Although several computer-aided colorectal polyp detection and diagnosis systems have been proposed for clinical application, many remain susceptible to interference problems, including low image clarity, unevenness, and low accuracy for the analysis of dynamic images; these drawbacks affect the robustness and practicality of these systems. This study proposed an intraprocedure alert system for colonoscopy examination developed on the basis of deep learning. The proposed system features blurred image detection, foreign body detection, and polyp detection modules facilitated by convolutional neural networks. The training and validation datasets included high-quality images and low-quality images, including blurred images and those containing folds, fecal matter, and opaque water. For the detection of blurred images and images containing folds, fecal matter, and opaque water, the accuracy rate was 96.2%. Furthermore, the study results indicated a per-polyp detection accuracy of 100% when the system was applied to video images. The recall rates for high-quality image frames and polyp image frames were 95.7% and 92%, respectively. The overall alert accuracy rate and the false-positive rate of low quality for video images obtained through per-frame analysis were 95.3% and 0.18%, respectively. The proposed system can be used to alert colonoscopists to the need to slow their procedural speed or to perform flush or lumen inflation in cases where the colonoscope is being moved too rapidly, where fecal residue is present in the intestinal tract, or where the colon has been inadequately distended.


Subject(s)
Artificial Intelligence , Colonic Polyps , Humans , Colonic Polyps/diagnostic imaging , Colonoscopy/methods , Neural Networks, Computer , Colon
4.
Cells ; 11(3)2022 01 30.
Article in English | MEDLINE | ID: mdl-35159293

ABSTRACT

Polycystic kidney disease (PKD) is one of the most common inherited diseases and is characterized by the development of fluid-filled cysts along multiple segments of the nephron. Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of PKD, which is caused by mutations in either PKD1 or PKD2 genes that encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively. As ADPKD progresses, cysts enlarge and disrupt normal kidney architecture, eventually leading to kidney failure. Our previous study showed that overexpression of exogenous kidney-specific neutrophil gelatinase-associated lipocalin (NGAL) reduced cyst progression and prolonged the lifespan of ADPKD mice (Pkd1L3/L3, 2L3 for short). In this study, we attempted to explore the underlying mechanism of reduced cyst progression in the presence of NGAL using immortalized 2L3 cells. The results of MTT and BrdU incorporation assays showed that recombinant mouse NGAL (mNGAL) protein significantly decreased the viability and proliferation of 2L3 cells. Flow cytometry and western blot analyses showed that mNGAL inhibited activation of the ERK and AKT pathways and induced apoptosis and autophagy in 2L3 cells. In addition, a 3D cell culture platform was established to identify cyst progression in 2L3 cells and showed that mNGAL significantly inhibited cyst enlargement in 2L3 cells. Overexpression of secreted mNGAL (pN + LS) and nonsecreted mNGAL (pN - LS) repressed cell proliferation and cyst enlargement in 2L3 cells and had effects on markers involved in proliferation, apoptosis, and autophagy. However, secreted mNGAL had a more pronounced and consistent effect than that of nonsecreted form. These results reveal that secreted mNGAL has stronger ability to inhibit cyst enlargement of ADPKD cells than that of nonsecreted form. These findings could help to identify strategies for the future clinical treatment of ADPKD.


Subject(s)
Cysts , Lipocalin-2 , Polycystic Kidney, Autosomal Dominant , Animals , Lipocalin-2/genetics , Mice , Polycystic Kidney, Autosomal Dominant/genetics , TRPP Cation Channels/genetics
5.
Sensors (Basel) ; 21(18)2021 Sep 07.
Article in English | MEDLINE | ID: mdl-34577209

ABSTRACT

Colonoscopy screening and colonoscopic polypectomy can decrease the incidence and mortality rate of colorectal cancer (CRC). The adenoma detection rate and accuracy of diagnosis of colorectal polyp which vary in different experienced endoscopists have impact on the colonoscopy protection effect of CRC. The work proposed a colorectal polyp image detection and classification system through grayscale images and deep learning. The system collected the data of CVC-Clinic and 1000 colorectal polyp images of Linkou Chang Gung Medical Hospital. The red-green-blue (RGB) images were transformed to 0 to 255 grayscale images. Polyp detection and classification were performed by convolutional neural network (CNN) model. Data for polyp detection was divided into five groups and tested by 5-fold validation. The accuracy of polyp detection was 95.1% for grayscale images which is higher than 94.1% for RGB and narrow-band images. The diagnostic accuracy, precision and recall rates were 82.8%, 82.5% and 95.2% for narrow-band images, respectively. The experimental results show that grayscale images achieve an equivalent or even higher accuracy of polyp detection than RGB images for lightweight computation. It is also found that the accuracy of polyp detection and classification is dramatically decrease when the size of polyp images small than 1600 pixels. It is recommended that clinicians could adjust the distance between the lens and polyps appropriately to enhance the system performance when conducting computer-assisted colorectal polyp analysis.


Subject(s)
Colonic Polyps , Colorectal Neoplasms , Deep Learning , Colonic Polyps/diagnostic imaging , Colonoscopy , Colorectal Neoplasms/diagnostic imaging , Humans , Neural Networks, Computer
6.
Digestion ; 101(3): 339-346, 2020.
Article in English | MEDLINE | ID: mdl-30982036

ABSTRACT

BACKGROUND: The Japan narrow-band imaging Expert Team (JNET) classification of colorectal polyps based on magnifying endoscopy is used in Japan, but not worldwide. The objective of this study was to clarify differences of diagnostic accuracy between JNET users in Japan and non-JNET users in other countries. METHODS: A total of 185 colorectal tumors were assessed. Six endoscopists (3 each from Japan and Taiwan) participated in the study. The Japanese endoscopists normally used the JNET classification and the Taiwanese endoscopists normally used the narrow-band imaging International Colorectal Endoscopic classification for diagnosis of colorectal tumors. After receiving a lecture on the JNET classification, they all observed one blue laser imaging magnified image per lesion and performed diagnosis based on the JNET classification. RESULTS: Diagnostic ability was equivalent for Type 1, Type 2A, and Type 2B. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value of Type 3 for deep submucosal invasive carcinoma was, respectively, 44.4, 98.3, 57.1, and 97.2% in Group J and 70.0, 94.7, 40.4, and 98.4% in Group T. The PPV for diagnosis of Type 3 with a high confidence was significantly higher in Group J than in Group T (81.8% [55.4-94.6] vs. 44.4% [33.6-50.9], p < 0.05). CONCLUSIONS: The PPV for Type 3 differed between the 2 groups, suggesting the need to become familiar with differentiation between Type 2B and Type 3.


Subject(s)
Colonic Polyps/diagnosis , Colonoscopy/instrumentation , Colorectal Neoplasms/diagnosis , Lasers , Narrow Band Imaging/instrumentation , Adult , Aged , Aged, 80 and over , Colon/diagnostic imaging , Colon/pathology , Colonic Polyps/pathology , Colonoscopy/methods , Colorectal Neoplasms/pathology , Female , Humans , Intestinal Mucosa/diagnostic imaging , Intestinal Mucosa/pathology , Japan , Male , Middle Aged , Narrow Band Imaging/methods , Neoplasm Grading , Predictive Value of Tests , Rectum/diagnostic imaging , Rectum/pathology , Taiwan , Young Adult
7.
Gastroenterol Res Pract ; 2019: 9832482, 2019.
Article in English | MEDLINE | ID: mdl-31611916

ABSTRACT

BACKGROUND: The association between gallbladder (GB) disease and colorectal precancerous lesions remains elusive. This study sought to explore the association between GB disease and colorectal neoplasms at different locations. METHODS: Patients who received general health checkup from January to December 2008 were included and subgrouped into three groups by polyp location: proximal, distal, and whole colon. GB disease and other known risk factors for colon cancer were compared and analyzed. Different types of polyps at different locations were further investigated. RESULTS: Of a total of 3136 patients (1776 men and 1360 women; mean age, 49.3 years) who had colon polyps, 212 (6.8%) had GB stone and 512 (16.3%) had GB polyps. Patients in the proximal colon polyp group had higher rates of GB polyps and stones. GB polyps were independently associated with proximal colon polyps, including both hyperplastic polyps (odds ratio, 1.523; P = 0.034) and adenomatous polyps (odds ratio, 1.351; P = 0.048). No relationship between GB polyps and distal or any colon polyps was observed. Irrespective of the polyp location (i.e., proximal, distal, or any part of the colon), GB stone did not show any association with colon polyp. CONCLUSIONS: We suggested that GB polyps are associated with proximal colon polyps. Colonoscopy may be a more effective strategy for screening proximal precancerous lesions among patients with GB polyps. The association between GB disease and colon polyps demands further prospective investigation.

8.
Kaohsiung J Med Sci ; 35(9): 572-577, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31162814

ABSTRACT

The polyp detection rate (PDR) is an important quality indicator for colonoscopy. Several factors have been shown to be associated with PDR. However, whether the moderate sedation is a factor for polyp detection remains controversial. This study aims to assess factors associated with polyp detection including the moderate sedation factor during colonoscopy. Patients who underwent colonoscopy from June 1, 2014 to May 31, 2015 were enrolled into this retrospective study. Patients with poor colon preparation and failure to reach the cecum were excluded. The clinical factors, including patient's sex, age, midazolam/fentanyl sedation, indications, endoscopist colonoscopy volume, and use of antispasmodic agent were evaluated by multivariate analysis. A total of 3373 patients were included in this study. The mean age was 55.8 years, and 1980 patients (58.7%) were male. Among the 3373 patients, 2513 (74.5%) underwent midazolam/fentanyl-based sedated colonoscopy. The multivariate analysis showed that male sex, age over 50 years old, midazolam/fentanyl sedation and indications of screening and surveillance were significantly associated with polyp detection. Moreover, when stratified by sex and age, the midazolam/fentanyl sedation was associated with polyp detection in male patients and patients over 50 years old. This study has highlighted the role of midazolam/fentanyl sedation administered by colonoscopists as a modifiable factor that may increase polyp detection during colonoscopy.


Subject(s)
Colonic Polyps/diagnostic imaging , Colonic Polyps/diagnosis , Colonoscopy , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Retrospective Studies
9.
EMBO J ; 37(20)2018 10 15.
Article in English | MEDLINE | ID: mdl-30177570

ABSTRACT

Expression of mitochondrial proton transporter uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) is essential for mammalian thermogenesis. While human UCP1 mRNA exists in a long form only, alternative polyadenylation creates two different isoforms in mice with 10% of UCP1 mRNA found in the long form (Ucp1L) and ~90% in the short form (Ucp1S). We generated a mouse model expressing only Ucp1S and found that it showed impaired thermogenesis due to a 60% drop in UCP1 protein levels, suggesting that Ucp1L is more efficiently translated than Ucp1S. In addition, we found that ß3 adrenergic receptor signaling promoted the translation of mouse Ucp1L and human Ucp1 in a manner dependent on cytoplasmic polyadenylation element binding protein 2 (CPEB2). CPEB2-knockout mice showed reduced UCP1 levels and impaired thermogenesis in BAT, which was rescued by ectopic expression of CPEB2. Hence, long 3'-UTR Ucp1 mRNA translation activated by CPEB2 is likely conserved and important in humans to produce UCP1 for thermogenesis.


Subject(s)
3' Untranslated Regions/physiology , Adipose Tissue, Brown/metabolism , Protein Biosynthesis/physiology , RNA-Binding Proteins/metabolism , Thermogenesis/physiology , Uncoupling Protein 1/biosynthesis , Animals , Ectopic Gene Expression , Female , Humans , Male , Mice , Mice, Knockout , Protein Isoforms/biosynthesis , Protein Isoforms/genetics , RNA-Binding Proteins/genetics , Receptors, Adrenergic, beta-3/genetics , Receptors, Adrenergic, beta-3/metabolism , Signal Transduction/physiology , Uncoupling Protein 1/genetics
10.
Ther Clin Risk Manag ; 14: 1331-1336, 2018.
Article in English | MEDLINE | ID: mdl-30104879

ABSTRACT

BACKGROUND: Subjects with obstructive sleep apnea (OSA) are vulnerable to sedation-related complications during endoscopic procedures. A significant portion of subjects undergoing routine endoscopy is at high risk of OSA, but most are undiagnosed. The purpose of this study was to estimate the prevalence of high risk for OSA among Chinese subjects undergoing deep sedation for screening gastrointestinal endoscopy and to evaluate the hypoxemia risk of these examinees stratified by Berlin Questionnaire (BQ). PATIENTS AND METHODS: We performed a prospective cohort study in subjects undergoing deep sedation with monitored anesthesia care for combined esophagogastroduodenoscopy plus colonoscopy. Subjects who were Chinese were stratified into high- and low-risk groups for OSA by administration of BQ. Deep sedation was achieved via a propofol target-controlled infusion system. Hypoxemia was defined as pulse oximetry reading of less than 90%. The frequency of hypoxemia was compared between high- and low-risk groups for OSA. RESULTS: A total of 615 Chinese subjects were recruited during the study period, and 614 subjects were included for analysis. Two hundred eighteen (35.5%) subjected were classified to be at high risk of OSA, and 396 (64.5%) were stratified to be at low risk of OSA by BQ. Hypoxemia occurred in 83 (13.5%) subjects during endoscopy procedures. The risk of developing hypoxemia in the high-risk group was significantly higher when compared to that of the low-risk group subjects (24.8% vs 7.3%; relative risk, 3.37; 95% CI, 2.22-5.13). CONCLUSION: About one-third Chinese subjects undergoing deep sedation for screening endoscopy were at high risk of OSA. Subjects at high risk of OSA are associated with an increased risk of hypoxemia in comparison to the low-risk group when undergoing deep sedation for screening gastrointestinal endoscopy.

11.
J Chin Med Assoc ; 81(12): 1033-1037, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29778549

ABSTRACT

BACKGROUND: Esophagogastroduodenoscopy (EGD) is a standard tool for detection of mucosal and submucosal lesions. However, identification of Helicobacter pylori (H. P) infection using EGD alone is limited in accuracy. Linked color imaging (LCI) is a novel tool to capture real-time image with sufficient contrast to observe mucosal microstructure. METHODS: This study aims to evaluate the applicability of LCI in the identification of H. pylori infection. Consecutive 122 patients scheduled for EGD were included. They were examined with LCI and magnifying endoscopy. The classification of H. pylori was based on pathology results of biopsy and rapid urease test or urea breath test. RESULTS: We compared the results based on LCI or magnifying endoscopy to reference classification. Of 122 patients, 36 had H. pylori infection (29.51%). The level of accuracy of diagnosis of H. pylori infections by LCI, magnifying endoscopy, and both LCI and magnifying endoscopy was 78.38%, 81.98%, and 78.38%, respectively. The sensitivity and specificity of each group were 70.97%, 81.25%, and 80.65% and 82.5%, 83.87%, and 76.25%, respectively. The positive predictive values were 59.46%, 64.10%, and 57.78%, respectively, and the negative predictive values were 87.84%, 91.67%, and 92.42%, respectively. CONCLUSION: LCI could be playing a valuable initial screen tool for real-time diagnosis of H. pylori infections. It has a high accuracy of diagnosis of H. pylori infections. Therefore, in patients suspected to have H. pylori infections using LCI, the infections need to be carefully diagnosed using appropriate methods because, as per the consensus, they should be eradicated as soon as possible before precancerous lesions develop.


Subject(s)
Gastric Mucosa/diagnostic imaging , Helicobacter Infections/diagnosis , Helicobacter pylori , Adult , Aged , Endoscopy, Gastrointestinal , Female , Humans , Male , Middle Aged
12.
Transl Res ; 200: 43-53, 2018 10.
Article in English | MEDLINE | ID: mdl-30670154

ABSTRACT

Implications of plasminogen activator inhibitor-1 (PAI-1) in colonic polyps remain elusive. A prospective study was conducted with 188 consecutive subjects who underwent colonoscopy at a tertiary referral center. Biochemical parameters, serum PAI-1 levels, PAI-1 single-nucleotide polymorphisms (rs-1799889), and colonic polyp profiles were analyzed at baseline and 24 and 48 weeks postpolypectomy. Of 188 patients (mean age: 56.8 years), 78.7% had adenomas; the median polyp number and size were 2 and 1.2cm, respectively. Multivariate analyses revealed the following baseline associations: PAI-1 levels (95% confidence interval [CI] for estimated ß: 0.012-0.223) and polyp pathology (0.294-0.63) with polyp size; polyp size (0.085-0.498) and platelet count (0.013-0.027) with PAI-1 levels. At 24 weeks postpolypectomy, homeostasis model assessment-estimated insulin resistance (HOMA-IR) and platelet count were independently associated with PAI-1 levels. Among patients with colonic adenomas, baseline PAI-1 levels (95% CI odds ratio: 1.06-1.686; cut-off value: >10.65 ng/mL, area under curve: 0.662, P = 0.032) and the PAI-1-rs-17998894G/4G genotype (0.036-0.912) were associated with high-grade dysplasia. Compared with baseline levels, repeated measures analysis of variance showed that PAI-1 levels increased, with concurrent increased HOMA-IR indexes, but decreased alanine transaminase levels and polyp size in follow-up colonoscopies at 24 weeks postpolypectomy. PAI-1 returned to baseline levels, and HOMA-IRs and triglyceride/high-density lipoprotein-cholesterol ratios decreased at 48 weeks postpolypectomy. Taken together, serum PAI-1 levels were positively associated with colonic polyp size and high-grade dysplasia, which was modulated by the PAI-1-rs-17998894G/4G genotype. The beneficial postpolypectomy inflammatory and metabolic alterations might be transiently counter regulated by elevated PAI-1 levels, with a link to HOMA-IR.


Subject(s)
Colonic Polyps/metabolism , Colonic Polyps/pathology , Plasminogen Activator Inhibitor 1/metabolism , Adenoma/genetics , Adenoma/metabolism , Adenoma/pathology , Adenoma/surgery , Aged , Alanine Transaminase/blood , Cholesterol, HDL/blood , Colonic Polyps/genetics , Colonic Polyps/surgery , Colonoscopy , Female , Genotype , Homeostasis , Humans , Insulin Resistance , Male , Middle Aged , Plasminogen Activator Inhibitor 1/blood , Platelet Count , Polymorphism, Single Nucleotide , Prospective Studies , ROC Curve , Triglycerides/blood
13.
Ther Clin Risk Manag ; 13: 1317-1321, 2017.
Article in English | MEDLINE | ID: mdl-29042789

ABSTRACT

INTRODUCTION: Linked-color imaging (LCI) is a recently developed system used in endoscopy. It creates clear and bright endoscopic images using short-wavelength, narrow-band laser light combined with white laser light. The illuminating light and signal processing emphasize slight color differences in abnormal regions that approximate the normal color of the mucosa. As a result, regions initially appearing red become a deeper shade of red, while regions originally appearing white become brighter, yet with natural tones. This process facilitates recognition of slight differences in the color of the mucosa and clarifies the boundaries of the mucosal pit. AIM: To determine whether LCI of the colon can improve the correlation between endoscopic findings and pathological diagnosis. METHODS: Consecutive patients who underwent colonoscopy requiring polypectomy or removal by biopsy forceps if possible were recruited. Probable polyp histology was assessed by two endoscopists using the Narrow-band imaging International Colorectal Endoscopic (NICE) classification and LCI data. All detected polyps were sent to the pathology department for pathological diagnosis by two pathologists. RESULTS: In total, 94 polyps were found in 43 patients. The sensitivity, specificity, positive predictive value, and negative predictive value for neoplastic lesion prediction (NICE type2/3) were 96.5%, 83.8%, 90.2%, and 93.9%, respectively. CONCLUSION: LCI combined with the NICE classification system is a powerful tool for predicting probable histology of colon polyps.

14.
Nutrients ; 9(6)2017 Jun 02.
Article in English | MEDLINE | ID: mdl-28574439

ABSTRACT

How hepatatitis C virus (HCV) infection affects the interplay among abundant adipokines in the host remains unclear. A prospective study was conducted with 450 consecutive genotype 1 (G1) and G2 HCV patients who completed a course of anti-HCV therapy and underwent pre-therapy and 24-week post-therapy surveys to assess various profiles and levels of abundant adipokines, including leptin, adiponectin, and plasminogen activator inhibitor-1 (PAI-1). Before anti-HCV therapy, multivariate analyses showed gender to be associated with leptin and adiponectin levels, and BMI with leptin and PAI-1 levels. Among patients with a sustained virological response (SVR, n = 372), associations at 24 weeks post-therapy were as follows: gender and BMI with all adipokine levels; hepatic steatosis and aspartate aminotransferase to platelet ratio index with adiponectin levels; and HOMA-IR and HCV genotype with PAI-1 levels. Paired t-tests revealed increased post-therapeutic PAI-1 levels in G1 SVR patients and decreased adiponectin levels in all SVR patients compared to pre-therapeutic levels. HCV infection may obscure associations between abundant adipokines and metabolic/hepatic profiles. In SVR patients, a higher hierarchical status of PAI-1 versus adiponectin in affecting glucose metabolism was noted at 24 weeks post-therapy. Such genotype-non-specific adiponectin decreases and G1-specific PAI-1 increases warrant careful follow-up of HCV patients after SVR according to viral genotype.


Subject(s)
Adipokines/blood , Hepatitis C/blood , Hepatitis C/drug therapy , Adult , Aged , Alanine Transaminase/blood , Antiviral Agents/therapeutic use , Aspartate Aminotransferases/blood , Body Mass Index , Cholesterol/blood , Fatty Liver/blood , Female , Follow-Up Studies , Hepatitis C Antibodies/blood , Humans , Male , Middle Aged , Plasminogen Activator Inhibitor 1/blood , Prospective Studies , Triglycerides/blood
15.
Virulence ; 8(7): 1255-1264, 2017 10 03.
Article in English | MEDLINE | ID: mdl-28267407

ABSTRACT

BACKGROUND: The evolution of the relationship between adiponectin and insulin sensitivity in hepatitis C virus (HCV) patients during viral clearance is unclear and warrants investigation. METHODS: A prospective study including 747 consecutive chronic hepatitis C (CHC) patients, of whom 546 had completed a course of anti-HCV therapy and underwent pre-, peri- and post-therapy surveys for anthropomorphic, viral, metabolic and hepatic profiles and adiponectin levels, was conducted in a tertiary care center. RESULTS: Multivariate analyses indicated associations of sex, triglyceride levels and hepatic steatosis with adiponectin levels and of triglyceride levels and interferon λ3 (IFNL3) genotype with homeostasis model assessment-estimated insulin resistance (HOMA-IR) levels before anti-HCV therapy. In patients with a sustained virological response (SVR; n = 455), at 24 weeks post-therapy, sex, BMI, aspartate aminotransferase to platelet ratio index (APRI), HOMA-IR and steatosis were associated with adiponectin levels, and IFNL3 genotype was associated with HOMA-IR levels. GEE analysis demonstrated that SVR affected longitudinal trends in adiponectin levels. Compared with pre-therapy levels, adiponectin and APRI levels decreased 24 weeks post-therapy in SVR patients, regardless of baseline insulin resistance (IR). However, HOMA-IR levels decreased in SVR patients with baseline IR but increased in those without baseline IR. Compared with controls, immunohistochemical studies showed that pre-therapy CHC patients had higher hepatic adiponectin expression associated with hepatic fibrosis. CONCLUSIONS: During HCV infection, adiponectin may affect insulin sensitivity through triglycerides. After viral clearance, adiponectin levels were directly associated with insulin sensitivity and decreased upon improved hepatic fibrosis; with a link to the IFNL3 genotype, insulin sensitivity improved only in patients with baseline IR.


Subject(s)
Adiponectin/metabolism , Antiviral Agents/therapeutic use , Hepacivirus/physiology , Hepatitis C, Chronic/metabolism , Insulin Resistance , Insulin/metabolism , Adiponectin/genetics , Adult , Aged , Female , Genotype , Hepacivirus/drug effects , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/genetics , Hepatitis C, Chronic/virology , Humans , Interferons , Interleukins/genetics , Interleukins/metabolism , Male , Middle Aged , Prospective Studies , Viral Load/drug effects
16.
Sci Rep ; 6: 30799, 2016 08 01.
Article in English | MEDLINE | ID: mdl-27477870

ABSTRACT

The effect of resistin (RETN) on the response to anti-HCV therapy remains unclear. A prospective cohort study was performed using 655 consecutive HCV patients, of whom 513 had completed a course of interferon-based therapy. Multivariate and GEE analyses revealed four RETN single-nucleotide polymorphisms (SNPs), rs34861192, rs3219175, rs3745367 and rs1423096, to be synergistically associated with resistin levels. After adjusting for co-factors such as interferon λ-3 (IFNL3)-rs12979860, the resistin level and the hyper-resistinemic genotype at the 4 RETN SNPs were positively and negatively associated with a sustained virological response (SVR), respectively. RETN-rs3745367 was in linkage disequilibrium with IFNL3-rs12979860. Compared to non-SVR patients, SVR patients had higher levels of pre-therapy resistin, primarily originating from intrahepatic lymphocytes, stellate cells, Kupffer cells, hepatic progenitor cells and hepatocytes. This difference diminished over the course of therapy, as only SVR patients exhibited a 24-week post-therapy decrease in resistin. Both resistin and IFNL3 mRNAs were upregulated, but only resistin mRNA was upregulated by recombinant resistin in peripheral blood mononuclear cells with and without hyper-resistinemic genotypes of the 4 RETN SNPs, respectively. Fine-tuned by RETN SNPs, intrahepatic, multi-cellular resistin reinforced IFNL3 in eliminating HCV via immunomodulation to counteract pro-inflammation. These results encourage the development of novel resistin-targeted anti-viral agents.


Subject(s)
Hepacivirus/immunology , Hepatitis C/genetics , Hepatitis C/immunology , Interleukins , Polymorphism, Single Nucleotide , Resistin , Adult , Female , Hepatitis C/therapy , Humans , Interferons , Interleukins/genetics , Interleukins/immunology , Male , Resistin/genetics , Resistin/immunology
17.
Medicine (Baltimore) ; 95(14): e3187, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27057845

ABSTRACT

We aimed to investigate the clinical characteristics of patients with herpes esophagitis (HE) based on endoscopic typing.Herpes simplex virus infection in the gastrointestinal tract primarily affects the esophagus. However, little is known about the presentation, endoscopic findings, and outcomes of HE.From 2003 to 2013, 47 patients with HE were identified histologically from among 1843 patients with esophageal ulcers. Personal data, underlying disease, esophagogastroduodenoscopy indication, endoscopic characteristics, pathological findings, laboratory data, and outcomes were collected. Endoscopic findings were classified into 3 types based on gross appearance and were correlated with clinical presentation.The mean age of patients was 62.04 ±â€Š14.76 years, and most patients were men (39/47, 83%). The most common symptoms were odynophagia/dysphagia (20/47, 42.6%). Whereas 25 patients (53.2%) were diagnosed with malignancy, it was related to human immunodeficiency virus in only 1 patient (2.1%). HE was classified into 3 types based on endoscopic images: type I (n = 19), type II (n = 10), and type III (n = 18). The majority of patients with HE type III had sepsis (72%) and obvious leukocytosis than the other 2 types (P = 0.03). The overall mortality rate was 6.4% (3/47), and most of the patients who died (66.7% [2/3]) belonged to the endoscopic classification type III group. Clinical parameters were analyzed for the risk of poor outcome. Postchemotherapy and/or radiotherapy were associated with 30-day mortality after appearance of HE (P < 0.05).Herpes esophagitis primarily affects men and patients with malignancy or sepsis. However, the disease is usually self-limiting, and HE-related mortality is low. Relationship between severity of endoscopic findings and patients' outcome remains questionable. Further prospective study is needed.


Subject(s)
Esophagitis/diagnosis , Esophagitis/virology , Herpes Simplex/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Esophagoscopy , Female , Humans , Male , Middle Aged , Prospective Studies , Taiwan , Young Adult
18.
Brain Res ; 1639: 132-48, 2016 05 15.
Article in English | MEDLINE | ID: mdl-26972528

ABSTRACT

Spinocerebellar ataxia type 17 (SCA17), an autosomal dominant cerebellar ataxia, is a devastating, incurable disease caused by the polyglutamine (polyQ) expansion of transcription factor TATA binding protein (TBP). The polyQ expansion causes misfolding and aggregation of the mutant TBP, further leading to cytotoxicity and cell death. The well-recognized prodromal phase in many forms of neurodegeneration suggests a prolonged period of partial neuronal dysfunction prior to cell loss that may be amenable to therapeutic intervention. The objective of this study was to assess the effects and molecular mechanisms of granulocyte-colony stimulating factor (G-CSF) therapy during the pre-symptomatic stage in SCA17 mice. Treatment with G-CSF at the pre-symptomatic stage improved the motor coordination of SCA17 mice and reduced the cell loss, insoluble mutant TBP protein, and vacuole formation in the Purkinje neurons of these mice. The neuroprotective effects of G-CSF may be produced by increases in Hsp70, Beclin-1, LC3-II and the p-ERK survival pathway. Upregulation of chaperone and autophagy levels further enhances the clearance of mutant protein aggregation, slowing the progression of pathology in SCA17 mice. Therefore, we showed that the early intervention of G-CSF has a neuroprotective effect, delaying the progression of SCA17 in mutant mice via increases in the levels of chaperone expression and autophagy.


Subject(s)
Granulocyte Colony-Stimulating Factor/pharmacology , Neuroprotective Agents/pharmacology , Prodromal Symptoms , Spinocerebellar Ataxias/drug therapy , Animals , Apoptosis/drug effects , Apoptosis/physiology , Autophagy/drug effects , Autophagy/physiology , Disease Models, Animal , Drug Evaluation, Preclinical , Extracellular Signal-Regulated MAP Kinases/metabolism , HSP70 Heat-Shock Proteins/metabolism , Mice, Transgenic , Microtubule-Associated Proteins/metabolism , Motor Activity/drug effects , Motor Activity/physiology , Purkinje Cells/drug effects , Purkinje Cells/pathology , Purkinje Cells/physiology , Spinocerebellar Ataxias/pathology , Spinocerebellar Ataxias/physiopathology
19.
Scand J Gastroenterol ; 51(3): 374-7, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26489709

ABSTRACT

BACKGROUND: Previous research shows that only 10-30% of gastrointestinal stromal tumors (GISTs) are malignant. Nonetheless, some reports suggest that all of them have some degree of potential for malignancy. Endoscopic ultrasonography (EUS) is a useful technique for differentiation of subepithelial lesions in the gastrointestinal tract. We explored EUS characteristics that might predict the malignancy potential of GISTs. METHODS: In this retrospective review of the medical records from 1999 through 2007, patients who had gastric stromal tumors diagnosed prior to surgery using EUS were enrolled. The EUS images, procedure records and tissue histopathology were reviewed. All patients were positive for C-kit. RESULTS: Of the 110 patients enrolled, 57 were males, and 53 were females. Most (67%) of the GISTs were located in the gastric body. The lesion size ranged from 6.3 to 150 mm (mean ± SD: 39.73 ± 22.49 mm). The high-risk GIST group had 19 (17.3%) patients, the intermediate-risk group had 12 (10.9%) patients and the low/very low-risk group had 79 (71.8%) patients. Thirty patients had cystic lesions (27.3%), while six patients had calcification in the lesion (5.5%). Additionally, 27 patients (24.5%) had surface ulceration visible on endoscopy. GISTs at high risk for malignancy were highly associated with lesion size (p < 0.0001), cystic change (p = 0.015) and surface ulceration (p = 0.036) but not with calcification (p = 0.667). We also found that mitosis was associated with lesion size (p < 0.0001) rather than other parameters. Age was not predictive of malignancy potential (p = 0.316). However, tumor size is the only one independent risk factor for malignancy (p ≤ 0.0001). CONCLUSIONS: The preliminary results show that large gastric GISTs with cystic change and surface ulceration may associate with a risk of malignancy, warranting more aggressive management. Nevertheless, the tumor size is more important than other factors.


Subject(s)
Calcinosis/diagnostic imaging , Endosonography , Gastrointestinal Stromal Tumors/diagnostic imaging , Gastrointestinal Stromal Tumors/pathology , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/pathology , Cell Transformation, Neoplastic , Cysts/diagnostic imaging , Female , Gastrointestinal Stromal Tumors/surgery , Humans , Male , Mitotic Index , Retrospective Studies , Risk Factors , Stomach Neoplasms/surgery , Tumor Burden
20.
Gastroenterol Res Pract ; 2015: 564536, 2015.
Article in English | MEDLINE | ID: mdl-26351451

ABSTRACT

Small bowel diverticulum is a rare cause of gastrointestinal bleeding. The diagnosis and treatment of small bowel diverticular hemorrhage is clinically challenging before the development of deep enteroscopy. In this multicenter study from the Taiwan Association for the Study of Small Intestinal Diseases (TASSID), 608 patients underwent deep enteroscopy for obscure gastrointestinal bleeding during January 2004 and April 2010 from eight medical centers in Taiwan. Small bowel diverticular hemorrhage account for 7.89% of obscure gastrointestinal bleeding in this study. Most of the patients received endoscopic therapy with an initial hemostasis rate of 85.71% and rebleeding rate of 20%. In this large case series investigating the enteroscopic management of small intestinal diverticular hemorrhage, we found that, as to patients with peptic ulcer hemorrhage, most of these patients can be successfully managed by endoscopic therapy before surgery in the era of deep enteroscopy.

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