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1.
J Sep Sci ; 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35524724

RESUMO

A method is firstly established for the separation and determination of fenpropathrin enantiomer residues in apple puree, strawberry puree, and tomato puree considered as a supplementary food for infants by supercritical fluid chromatography. After the sample was extracted with acetonitrile and cleaned up by a solid phase extraction column, then it's separated by a CHIRALPAK AD-3 chiral column with a gradient elution at a flow rate of 1.0 mL/min using methanol and supercritical carbon dioxide as the mobile phase, detected by ultraviolet detector at 230 nm wavelength and quantified with the external standard method. The limits of quantification of the two fenpropathrin enantiomers were both 0.2 mg/kg, the linear ranges were 1.0-20.0 mg/L with linear correlation coefficients greater than 0.9992, the recoveries in the spiked samples at 0.2, 0.4 and 2.0 mg/kg were from 80.6% to 105%, and the relative standard deviation reached 2.6%-7.7%. This method has the advantages of convenient operation, good resolution and environmental protection, which can satisfy the requirement of determination for fenpropathrin enantiomer residues in fruit and vegetable puree as a supplementary food for infants. This article is protected by copyright. All rights reserved.

2.
Therap Adv Gastroenterol ; 15: 17562848221092597, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35509421

RESUMO

Background: Mucosal healing (MH) is considered the preferred therapeutic target for ulcerative colitis (UC). Impaired quality of life (QoL), irritable bowel syndrome (IBS)-like symptoms, and functional bowel symptoms have been reported in several inactive patients with UC. This study aims to assess the occurrence of functional bowel disorders (FBD)-like symptoms and QoL in UC patients with MH, and to explore the factors related to FBD-like symptoms. Methods: UC patients with MH (Mayo endoscopic score, MES = 0 or 1) were required to complete the Rome IV diagnostic questionnaire, the 32-item version of Inflammatory Bowel Disease Questionnaire (IBDQ-32), the 36-item short form healthy survey questionnaire (SF-36), and the Hospital Anxiety and Depression Scale (HADS). UC patients who did not achieve MH (MES > 1) completed the IBDQ-32, the SF-36, and the HADS. Community-dwelling healthy controls (HCs) completed the SF-36 and the HADS. Results: Among the 119 UC patients with MH recruited, 45.4% reported functional bowel symptoms; functional constipation-like symptom (13.4%) was the most prevalent, followed by IBS-like symptom (10.9%), and functional diarrhea-like symptom (10.0%). The IBDQ-32 and SF-36 scores were significantly lower in MH patients with FBD-like symptoms than in those without FBD-like symptoms. Disease duration [odds ratio (OR): 1.022; p < 0.001], body mass index (BMI; OR: 0.726; p < 0.001) were independent predictors of FBD-like symptoms in UC patients with MH. Combining these two factors could attain area under the curve [0.786; 95% confidence interval (CI): 0.701-0.856, p < 0.001] to predict FBD-like symptoms in MH patients. Conclusion: A number of UC patients with MH had accompanying FBD-like symptoms and significantly impaired QoL. Disease duration, BMI could predict the occurrence of FBD-like symptoms.

4.
J Med Internet Res ; 24(3): e28978, 2022 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-35323120

RESUMO

BACKGROUND: Telemedicine plays an important role in the management of inflammatory bowel disease (IBD), particularly during a pandemic such as COVID-19. However, the effectiveness and efficiency of telemedicine in managing IBD are unclear. OBJECTIVE: This systematic review and meta-analysis aimed to compare the impact of telemedicine with that of standard care on the management of IBD. METHODS: We systematically searched the PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus databases on April 22, 2020. Randomized controlled trials comparing telemedicine with standard care in patients with IBD were included, while conference abstracts, letters, reviews, laboratory studies, and case reports were excluded. The IBD-specific quality of life (QoL), disease activity, and remission rate in patients with IBD were assessed as primary outcomes, and the number of in-person clinic visits per patient, patient satisfaction, psychological outcome, and medication adherence were assessed as secondary outcomes. Review Manage 5.3 and Stata 15.1 were used for data analysis. RESULTS: A total of 17 randomized controlled trials (2571 participants) were included in this meta-analysis. The telemedicine group had higher IBD-specific QoL than the standard care group (standard mean difference 0.18, 95% CI 0.01 to 0.34; P.03). The number of clinic visits per patient in the telemedicine group was significantly lower than that in the standard care group (standard mean difference -0.71, 95% CI -1.07 to -0.36; P<.001). Subgroup analysis showed that adolescents in the telemedicine group had significantly higher IBD-specific QoL than those in the standard care group (standard mean difference 0.42, 95% CI 0.15 to 0.69; I2=0; P.002), but there was no significant difference between adults in the 2 groups. There were no significant differences in disease activity, remission rate, patient satisfaction, depression, self-efficacy, generic QoL, and medication adherence outcomes between the telemedicine and standard care groups. CONCLUSIONS: Telemedicine intervention showed a promising role in improving IBD-specific QoL among adolescents and decreased the number of clinic visits among patients with IBD. Further research is warranted to identify the group of patients with IBD who would most benefit from telemedicine.


Assuntos
COVID-19 , Doenças Inflamatórias Intestinais , Telemedicina , Adolescente , Adulto , Humanos , Doenças Inflamatórias Intestinais/terapia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Artigo em Inglês | MEDLINE | ID: mdl-35272029

RESUMO

BACKGROUND & AIMS: Corticosteroids are the mainstay of treatment for hospitalized patients with acute severe ulcerative colitis (ASUC). However, whether the addition/continuation of mesalamine with corticosteroids during hospitalization is superior to corticosteroids alone is unknown. METHODS: This was a randomized controlled, investigator-blinded, clinical trial conducted in 10 centers in 7 countries. Patients hospitalized with ASUC (Lichtiger score ≥10) were eligible. Patients received corticosteroids alone or corticosteroid + mesalamine (4 g/day mesalamine) by a stratified randomization according to mesalamine use before admission. The primary outcome was the percentage of patients who responded to treatment by day 7, defined by a drop >3 points in the Lichtiger score and an absolute score <10 without the need for rescue medications or colectomy. RESULTS: Three hundred forty-six patients were screened, and 149 were included (70/149 female; median age, 41 years). Of these, 73 received corticosteroids + mesalamine, and 76 received corticosteroids alone. For the primary outcome, 53 of 73 patients (72.6%) receiving corticosteroids with mesalamine responded versus 58 of 76 patients (76.3%) on corticosteroids alone (odds ratio, 0.82; 95% confidence interval, 0.39-1.72; P = .60). There was no difference between groups in duration of hospitalization, C-reactive protein normalization rate, or colectomy rate up to day 90. The need for biologics among patients receiving combination of corticosteroids with mesalamine was numerically lower by day 30 (P = .11) and day 90 (P = .07). CONCLUSIONS: In this randomized controlled trial, combination of mesalamine with corticosteroids did not benefit hospitalized patients with ASUC more than corticosteroids alone. An exploratory signal for a reduced need for biologics at 90 days in the mesalamine group merits further evaluation. CLINICALTRIALS: gov ID: NCT01941589.

6.
Dis Esophagus ; 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35291006

RESUMO

BACKGROUND: To date, the ideal endoscopic knife for peroral endoscopic myotomy (POEM) with good performance and cost-effectiveness is still under investigation. The present study was aimed to evaluate the efficacy, safety, and cost-effectiveness of snare-assisted POEM, compared with the conventional endoscopic knife approach. METHODS: From May 2017 to December 2018, patients with achalasia presenting for POEM without previous endoscopic or surgical therapy were prospectively recruited in this randomized controlled trial. Patients were randomly allocated to receive POEM using either the snare (snare group) or HookKnife (conventional group). The primary outcome was clinical success (Eckardt score ≤ 3) at 12-month follow-up, powered for noninferiority with a margin of -15%. The secondary outcomes included adverse events (AEs), procedure-related parameters, clinical outcomes, and cost-effectiveness. RESULTS: A total of 75 patients with similar baseline characteristics between the snare (N = 37) and conventional (N = 38) groups were included. Clinical success at 12-month follow-up was achieved in 94.6% of patients in the snare group and 92.1% of patients in the conventional group (difference, 2.5% [95% CI, -8.7% to 13.7%]; P < 0.001 for noninferiority). No severe AEs occurred in both groups. The use of snare is associated with comparable procedure time (40.6 minutes vs. 42.5 minutes, P = 0.337), a lower frequency of hemostatic forceps use (27.0% vs. 68.4%, P < 0.001), and lower hospital costs ($4271.1 vs. $5327.3, P < 0.001). The cost-effectiveness plane revealed that 96.9% of snare-assisted POEM procedures offered more cost-savings and health utility benefits. CONCLUSIONS: The snare-assisted POEM was noninferior to the conventional endoscopic knife approach in terms of clinical efficacy, with comparable safety outcomes and cost-effective benefits.

7.
Inflamm Bowel Dis ; 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35247049

RESUMO

The number of patients with inflammatory bowel disease (IBD) has increased remarkably in recent years. However, the level of healthcare for IBD patients varies greatly among regions of China. Standardization of healthcare for IBD patients is essential to improve quality of care (QoC). The mission of the IBD Quality Care Evaluation Center (IBDQCC) is to establish indicators for QoC. Since 2017, the IBDQCC has developed structure, process, and outcome indicators with the steering committee of IBD specialists and methodologists; 28 core and 13 secondary IBD QoC indicators were selected using a Delphi methodology. Applications for certification of IBD quality care units were made voluntarily and preliminarily screened through the IBDQCC committee. "Regional" units had to meet all core indicators, and "excellence" units were required to meet all core indicators together with an additional 50% of secondary indicators. As of 2019 and 2020, 69 IBD units (all from tertiary referral hospitals) have been certified as regional IBD units in China. The certification of excellence of the IBD units is currently undergoing auditing. The awareness of and appreciation for QoC in IBD is increasing in China, especially through the quality control evaluation program initiated by the IBDQCC, with a higher number of IBD units applying for the next round of certification. Although secondary indicators seem to play relatively minor roles in QoC, they suggest additional requirements for high level centers.

8.
Medicine (Baltimore) ; 101(4): e28662, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35089209

RESUMO

INTRODUCTION: It is challenging to obtain favorable results through conventional diagnostic testing for Ureaplasma parvum (UP), a conditional pathogen, because of the atypical clinical phenotype of UP meningitis. PATIENT CONCERNS AND DIAGNOSIS: Herein, we report a pediatric case of neonatal meningitis caused by UP in a spontaneously delivered full-term baby. The infant's temperature peak was 38.3°C at the age of 9 days. The patient was diagnosed with neonatal suppurative meningitis. INTERVENTIONS AND OUTCOMES: The pathogen was diagnosed in a timely and accurate manner by metagenome sequencing, and the patient was eventually discharged with azithromycin. CONCLUSIONS: Neonatal Ureaplasma meningitis may be more common than previously suspected. The clinical manifestations were not obvious and were similar to those of neonatal meningitis caused by other bacteria. When conventional treatments and conventional pathogenic tests are negative, mNGS is a better choice for timely and accurate pathogen identification.


Assuntos
Meningites Bacterianas/diagnóstico , Metagenômica , Ureaplasma/genética , Adulto , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Criança , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Recém-Nascido , Doenças do Recém-Nascido , Meningites Bacterianas/congênito , Meningites Bacterianas/tratamento farmacológico , Metagenoma , Reação em Cadeia da Polimerase , Ureaplasma/isolamento & purificação
9.
Inflamm Bowel Dis ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34984455

RESUMO

BACKGROUND: Early changes in bowel behavior during anti-TNF induction therapy in Crohn's disease (CD) are relatively unknown. We determined (a) onset of changes in bowel behavior in CD patients receiving anti-TNF therapy by ultrasound; and (b) the feasibility of shear wave elastography (SWE) in predicting early response to anti-TNF therapy. METHODS: Consecutive ileal/ileocolonic CD patients programmed to initiate anti-TNF therapy were enrolled. Bowel ultrasound was performed at baseline, and at weeks 2, 6, and 14. Changes in bowel wall thickness, Doppler signals of the bowel wall (Limberg score), and SWE values were compared using a linear mixed model. Early response to anti-TNF therapy was based on a composite strategy of clinical and colonoscopy assessment at week 14. RESULTS: Of the 30 patients enrolled in this study, 20 patients achieved a response to anti-TNF therapy at week 14. The bowel wall thickness and SWE value of the response group showed a significant downward trend compared with the non-response group (P=0.003, P=0.011). Bowel wall thickness, the Limberg score, and SWE values were significantly reduced as early as week 2 compared with baseline (P<0.001, P<0.001, P=0.003) in the response group. Baseline SWE values (21.3±8.7 vs. 15.3±4.7 kPa, P=0.022) and bowel wall thickness (8.5±2.3 vs. 6.9±1.5 mm, P=0.027) in the non-response group were significantly higher than in the response group. CONCLUSIONS: This pilot study suggested that changes in bowel ultrasound behavior could be assessed as early as week 2 after starting anti-TNF therapy. Bowel ultrasound together with elasticity imaging could predict early response to anti-TNF therapy.

10.
Physiol Rev ; 102(2): 605-652, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34569264

RESUMO

Intestinal fibrosis is considered an inevitable complication of Crohn's disease (CD) that results in symptoms of obstruction and stricture formation. Endoscopic or surgical treatment is required to treat the majority of patients. Progress in the management of stricturing CD is hampered by the lack of effective antifibrotic therapy; however, this situation is likely to change because of recent advances in other fibrotic diseases of the lung, liver, and skin. In this review, we summarize data from randomized controlled trials (RCTs) of antifibrotic therapies in these conditions. Multiple compounds have been tested for antifibrotic effects in other organs. According to their mechanisms, they were categorized into growth factor modulators, inflammation modulators, 5-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, intracellular enzymes and kinases, renin-angiotensin system (RAS) modulators, and others. From our review of the results from the clinical trials and discussion of their implications in the gastrointestinal tract, we have identified several molecular candidates that could serve as potential therapies for intestinal fibrosis in CD.


Assuntos
Constrição Patológica/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Inflamação/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Constrição Patológica/diagnóstico , Doença de Crohn/diagnóstico , Fibrose/tratamento farmacológico , Humanos , Inflamação/patologia , Intestinos/efeitos dos fármacos , Intestinos/patologia
11.
Aliment Pharmacol Ther ; 55(3): 266-276, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34820868

RESUMO

BACKGROUND: While the incidence of inflammatory bowel disease (IBD) has stabilised in the West, it is still increasing in several newly industrialised countries. AIMS: To investigate whether the environmental and dietary risk factors for IBD differ between Eastern and Western populations METHODS: We systematically searched PubMed, Embase, and Web of Science for studies published from inception through June 30, 2020. Data were pooled using a random effects model. RESULTS: Overall, 255 studies were assessed. We identified 25 risk factors for IBD, seven of which were noted in both Eastern and Western populations: family history of Crohn's disease [CD] or ulcerative colitis [UC], former smoking (CD/UC), smoking (CD), appendicectomy (CD), tonsillectomy (CD), meat and meat products (CD), and vitamin D deficiency (UC). The remaining factors, including urban living, current smoking, antibiotics, oral contraceptives, caesarean section, isotretinoin, total energy, fat, cholesterol, fatty acids and their sub-classifications, eggs, and soft drinks, were associated with an increased risk of IBD in Western or Eastern populations only. We identified 21 protective factors for IBD, among which eight were common in the East and West: farm animals (CD/UC), Helicobacter pylori infection (CD/UC), multiple births (CD), physical activity (CD), history of breastfeeding (CD), pets (UC), current smoking (UC), and coffee intake (UC). Ten factors conferred protection against IBD in Western populations only, whereas eight factors conferred protection against IBD in Eastern populations only. CONCLUSIONS: Numerous environmental and dietary factors influenced the development of IBD in both Western and Eastern populations, whereas certain factors influenced IBD risk differently in these populations.


Assuntos
Colite Ulcerativa , Infecções por Helicobacter , Helicobacter pylori , Doenças Inflamatórias Intestinais , Animais , Cesárea , Colite Ulcerativa/epidemiologia , Feminino , Infecções por Helicobacter/complicações , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/etiologia , Gravidez , Fatores de Risco
12.
Gastroenterology ; 162(2): 482-494, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34757139

RESUMO

BACKGROUND AND AIMS: Starting biologic treatment early in the course of inflammatory bowel disease (IBD) may be associated with higher efficacy, especially in Crohn's disease (CD). METHODS: This was a systematic review and individual-patient data meta-analysis of all placebo-controlled trials of biologics approved for IBD at study inception (October 2015), using Vivli data-sharing platform. The primary outcome was the proportional biologic/placebo treatment effect on induction of remission in patients with short-duration (≤18 months) vs long-duration disease (>18 months) analyzed separately for CD and ulcerative colitis (UC). We used meta-regression to examine the impact of patients' characteristics on the primary outcome. RESULTS: We included 25 trials, testing infliximab, adalimumab, certolizumab, golimumab, natalizumab, or vedolizumab (6168 patients with CD and 3227 patients with UC). In CD, remission induction rates were higher in pooled placebo and patients in active arms with short-duration disease of ≤18 months (41.4% [244 of 589]) compared with disease duration of >18 months (29.8% [852 of 2857], meta-analytically estimated odds ratio, 1.33; 95% confidence interval, 1.09-1.64). The primary outcome, proportional biologic/placebo treatment effect on induction of remission, was not different in short-duration disease of ≤18 months (n = 589, odds ratio, 1.47; 95% confidence interval, 1.01-2.15) compared with longer disease duration (n = 2857, odds ratio, 1.43; 95% confidence interval, 1.19-1.72). In UC trials, both the proportional biologic/placebo remission-induction effect and the pooled biologic-placebo effect were stable, regardless of disease duration. Primary outcome results remained unchanged when tested using alternative temporal cutoffs and when modeled for individual patient's covariates, including prior anti-tumor necrosis factor exposure. CONCLUSIONS: There are higher rates of induction of remission with biologics and with placebo in early CD, resulting in a treatment to placebo effect ratio that is similar across disease durations. No such relationships between disease duration and outcomes was found in UC. PROSPERO registration: CRD42018041961.


Assuntos
Produtos Biológicos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adalimumab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Certolizumab Pegol/uso terapêutico , Colite Ulcerativa/fisiopatologia , Doença de Crohn/fisiopatologia , Fármacos Gastrointestinais/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Infliximab/uso terapêutico , Natalizumab/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Gut ; 71(3): 479-486, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33952604

RESUMO

OBJECTIVE: Effective medical therapy and validated trial outcomes are lacking for small bowel Crohn's disease (CD) strictures. Histopathology of surgically resected specimens is the gold standard for correlation with imaging techniques. However, no validated histopathological scoring systems are currently available for small bowel stricturing disease. We convened an expert panel to evaluate the appropriateness of histopathology scoring systems and items generated based on panel opinion. DESIGN: Modified RAND/University of California Los Angeles methodology was used to determine the appropriateness of 313 candidate items related to assessment of CD small bowel strictures. RESULTS: In this exercise, diagnosis of naïve and anastomotic strictures required increased bowel wall thickness, decreased luminal diameter or internal circumference, and fibrosis of the submucosa. Specific definitions for stricture features and technical sampling parameters were also identified. Histopathologically, a stricture was defined as increased thickness of all layers of the bowel wall, fibrosis of the submucosa and bowel wall, and muscularisation of the submucosa. Active mucosal inflammatory disease was defined as neutrophilic inflammation in the lamina propria and any crypt or intact surface epithelium, erosion, ulcer and fistula. Chronic mucosal inflammatory disease was defined as crypt architectural distortion and loss, pyloric gland metaplasia, Paneth cell hyperplasia, basal lymphoplasmacytosis, plasmacytosis and fibrosis, or prominent lymphoid aggregates at the mucosa/submucosa interface. None of the scoring systems used to assess CD strictures were considered appropriate for clinical trials. CONCLUSION: Standardised assessment of gross pathology and histopathology of CD small bowel strictures will improve clinical trial efficiency and aid drug development.


Assuntos
Doença de Crohn/patologia , Obstrução Intestinal/patologia , Intestino Grosso/patologia , Consenso , Constrição Patológica , Doença de Crohn/complicações , Humanos , Obstrução Intestinal/etiologia , Índice de Gravidade de Doença , Inquéritos e Questionários
15.
Gut ; 71(1): 55-67, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33468536

RESUMO

OBJECTIVE: Creeping fat, the wrapping of mesenteric fat around the bowel wall, is a typical feature of Crohn's disease, and is associated with stricture formation and bowel obstruction. How creeping fat forms is unknown, and we interrogated potential mechanisms using novel intestinal tissue and cell interaction systems. DESIGN: Tissues from normal, UC, non-strictured and strictured Crohn's disease intestinal specimens were obtained. The muscularis propria matrisome was determined via proteomics. Mesenteric fat explants, primary human preadipocytes and adipocytes were used in multiple ex vivo and in vitro cell migration systems on muscularis propria muscle cell derived or native extracellular matrix. Functional experiments included integrin characterisation via flow cytometry and their inhibition with specific blocking antibodies and chemicals. RESULTS: Crohn's disease muscularis propria cells produced an extracellular matrix scaffold which is in direct spatial and functional contact with the immediately overlaid creeping fat. The scaffold contained multiple proteins, but only fibronectin production was singularly upregulated by transforming growth factor-ß1. The muscle cell-derived matrix triggered migration of preadipocytes out of mesenteric fat, fibronectin being the dominant factor responsible for their migration. Blockade of α5ß1 on the preadipocyte surface inhibited their migration out of mesenteric fat and on 3D decellularised intestinal tissue extracellular matrix. CONCLUSION: Crohn's disease creeping fat appears to result from the migration of preadipocytes out of mesenteric fat and differentiation into adipocytes in response to an increased production of fibronectin by activated muscularis propria cells. These new mechanistic insights may lead to novel approaches for prevention of creeping fat-associated stricture formation.


Assuntos
Adipócitos/patologia , Movimento Celular , Doença de Crohn/patologia , Intestinos/patologia , Músculo Liso/patologia , Adipogenia/fisiologia , Tecido Adiposo/patologia , Diferenciação Celular , Células Cultivadas , Matriz Extracelular/patologia , Fibronectinas/metabolismo , Humanos , Tecidos Suporte
16.
Front Mol Biosci ; 8: 762355, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34859052

RESUMO

Fibrostenosis is a serious complication of Crohn's disease (CD), affecting approximately one-half of all patients. Surgical resection is the typical clinical end due to ineffective antifibrotic therapy mainly through anti-inflammatory treatment and fibrosis can be reverted only at early stages. Mover, human fibrotic disorders is known to be associated with aging process. Thus, accurate monitoring of the progression of fibrosis is crucial for CD management as well as can be benefit to aging related fibrosis. The excessive deposition of type I collagen (ColI) is the core point in major complications of fibrosis, including that in patients with CD and aging related fibrosis. Therefore, a MR imaging probe (EP-3533) targeted ColI was employed to stage bowel fibrosis in CD using a rat model and to compare its efficiency with the common MR imaging contrast medium gadopentetatedimeglumine (Gd-DTPA). The bowel fibrotic rat model was established with different degrees of bowel fibrosis, were scanned using a 3.0-T MRI scanner with a specialized animal coil. MRI sequence including T 1 mapping and T1-weighed imaging were performed before and after injecting the MRI probe (EP-3533 or Gd-DTPA). The T 1 relaxation time (T 1 value) and change in the contrast-to-noise ratio (ΔCNR) were measured to evaluate bowel fibrosis. Masson's trichrome staining was performed to determine the severity of fibrosis. EP-3533 offered a better longitudinal relaxivity (r1) with 67.537 L/mmol·s, which was approximately 13 times that of Gd-DTPA. The T 1 value on bowel segments was reduced in the images from EP-3533 compared to that from Gd-DTPA (F = 16.478; p < 0.001). Additionally, a better correlation between ΔCNR calculated from EP-3533 imaging and bowel fibrosis (AUC = 0.846) was determined 10 min after enhanced media administration than with Gd-DTPA (AUC = 0.532). The 10th-minute ΔCNR performed using the ColI probe showed the best correlation with the severity of bowel fibrosis (r = 0.538; p = 0.021). Our results demonstrates that targeted MRI probe (EP-3533) supplies a better enhanced effect compared to Gd-DTPA and could be a promising method to evaluate the progression and monitor the therapeutic response of bowel fibrosis.

17.
Gut Liver ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34593670

RESUMO

BACKGROUND/AIMS: Little is known about the clinical course of hepatitis B virus (HBV)-infected patients undergoing anti-tumor necrosis factor α (TNF-α) therapy for inflammatory bowel disease (IBD). We aimed to investigate the clinical course of HBV infection and IBD and to analyze liver dysfunction risks in patients undergoing anti-TNF-α therapy. METHODS: This retrospective multinational study involved multiple centers in Korea, China, Taiwan, and Japan. We enrolled IBD patients with chronic or resolved HBV infection, who received anti-TNF-α therapy. The patients' medical records were reviewed, and data were collected using a web-based case report form. RESULTS: Overall, 191 patients (77 ulcerative colitis and 114 Crohn's disease) were included, 28.3% of whom received prophylactic antivirals. During a median follow-up duration of 32.4 months, 7.3% of patients experienced liver dysfunction due to HBV reactivation. Among patients with chronic HBV infection, the proportion experiencing liver dysfunction was significantly higher in the non-prophylaxis group (26% vs 8%, p=0.02). Liver dysfunction occurred in one patient with resolved HBV infection. Antiviral prophylaxis was independently associated with an 84% reduction in liver dysfunction risk in patients with chronic HBV infection (odds ratio, 0.16; 95% confidence interval, 0.04 to 0.66; p=0.01). The clinical course of IBD was not associated with liver dysfunction or the administration of antiviral prophylaxis. CONCLUSIONS: Liver dysfunction due to HBV reactivation can occur in HBV-infected IBD patients treated with anti-TNF-α agents. Careful monitoring is needed in these patients, and antivirals should be administered, especially to those with chronic HBV infection.

18.
Biosensors (Basel) ; 11(9)2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34562892

RESUMO

In this study, we investigated the utility of native T1 mapping in differentiating between various grades of fibrosis and compared its diagnostic accuracy to magnetization transfer imaging (MTI) in a rat model of CD. Bowel specimens (64) from 46 CD model rats undergoing native T1 mapping and MTI were enrolled. The longitudinal relaxation time (T1 value) and normalized magnetization transfer ratio (MTR) were compared between none-to-mild and moderate-to-severe fibrotic bowel walls confirmed by pathological assessments. The results showed that the correlation between the T1 value and fibrosis (r = 0.438, p < 0.001) was lower than that between the normalized MTR and fibrosis (r = 0.623, p < 0.001). Overall, the T1 values (t = -3.066, p = 0.004) and normalized MTRs (z = 0.081, p < 0.001) in none-to-mild fibrotic bowel walls were lower than those in moderate-to-severe fibrotic bowel walls. The area under the curve (AUC) of the T1 value (AUC = 0.716, p = 0.004) was significantly lower than that of the normalized MTR (AUC = 0.881, p < 0.001) in differentiating moderate-to-severe fibrosis from none-to-mild fibrosis (z = -2.037, p = 0.042). Our results support the view that the T1 value could be a promising imaging biomarker in grading the fibrosis severity of CD. However, the diagnostic performance of native T1 mapping was not superior to MTI.


Assuntos
Doença de Crohn , Fibrose , Animais , Biomarcadores , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/patologia , Intestinos/patologia , Imageamento por Ressonância Magnética , Ratos
19.
Mol Med ; 27(1): 119, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556023

RESUMO

BACKGROUND: While anti-tumor necrosis factor alpha (TNF-α) therapy has been proven effective in inflammatory bowel disease (IBD), approximately 40% of patients lose the response. Transmembrane TNF-α (mTNF-α) expression in the intestinal mucosa is correlated with therapeutic efficacy, and quantification of mTNF-α expression is significant for predicting response. However, conventional intravenous application of microbubbles is unable to assess mTNF-α expression in intestinal mucosa. Herein, we proposed intracolic ultrasound molecular imaging with TNF-α-targeted microbubbles (MBTNF-α) to quantitatively detect mTNF-α expression in the intestinal mucosa. METHODS: MBTNF-α was synthesized via a biotin-streptavidin bridging method. TNF-α-targeted ultrasound imaging was performed by intracolic application of MBTNF-α to detect mTNF-α expression in surgical specimens from a murine model and patients with IBD. Linear regression analyses were performed to confirm the accuracy of quantitative targeted ultrasound imaging. RESULTS: On quantitative TNF-α-targeted ultrasound images, a greater signal intensity was observed in the mouse colons with colitis ([1.96 ± 0.45] × 106 a.u.) compared to that of the controls ([0.56 ± 0.21] × 106 a.u., P < 0.001). Targeted US signal intensities and inflammatory lesions were topographically coupled in mouse colons. Linear regression analyses in specimens of mice and patients demonstrated significant correlations between the targeted ultrasound signal intensity and mTNF-α expression (both P < 0.001). Furthermore, TNF-α-targeted ultrasound imaging qualitatively distinguished the varying inflammatory severity in intestinal specimens from IBD patients. CONCLUSION: Intracolic ultrasound molecular imaging with MBTNF-α enables quantitative assessment of mTNF-α expression. It may be a potential tool for facilitating the implementation of personalized medicine in IBD.


Assuntos
Colite/diagnóstico por imagem , Colo/diagnóstico por imagem , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Mucosa Intestinal/diagnóstico por imagem , Fator de Necrose Tumoral alfa/metabolismo , Ultrassonografia/métodos , Animais , Colite/induzido quimicamente , Colite/metabolismo , Colo/metabolismo , Colo/patologia , Modelos Animais de Doenças , Imunofluorescência , Expressão Gênica , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/metabolismo , Modelos Lineares , Masculino , Camundongos Endogâmicos BALB C , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ácido Trinitrobenzenossulfônico , Fator de Necrose Tumoral alfa/genética
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