Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 346
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-35505467

RESUMO

BACKGROUND: Keverprazan is a novel potassium-competitive acid blocker (P-CAB) with a strong acid-suppressive capacity that may provide clinical benefit in acid-related diseases. AIMS: This study aimed to explore the non-inferior efficacy and safety of keverprazan to lansoprazole in treating erosive oesophagitis (EO). METHODS: This was a phase III, randomised, double-blind multicentre study. Patients were randomised to receive keverprazan 20 mg once daily or lansoprazole 30 mg once daily for 4-8 weeks. EO healing rates and adverse events (AEs) were compared between the keverprazan group and the lansoprazole group. RESULTS: A total of 238 patients comprised the full analysis set (FAS) while 221 patients comprised the per-protocol set (PPS). For FAS analysis, the EO healing rates at week 8 were 95.8% (114/119) and 89.9% (107/119) for keverprazan and lansoprazole respectively. For PPS analysis, the EO healing rates at week 8 were 99.1% (110/111) and 92.7% (102/110) for keverprazan and lansoprazole respectively. Non-inferiority of keverprazan compared with lansoprazole according to EO healing rates at 8 weeks was demonstrated in both FAS (difference: 5.8% [95% CI: -0.6% to 12.3%]; p = 0.081) and PPS (difference: 6.1% [95% CI: 1.1%-11.2%]; p = 0.018) analysis. Drug-related AEs were reported in 34.5% (41/119) patients of the keverprazan group and 25.2% (30/119) patients of the lansoprazole group with no significant difference (p = 0.156). No severe AE happened in the keverprazan group. CONCLUSIONS: This study demonstrated the non-inferior efficacy of keverprazan to lansoprazole in treating EO. The incidences of drug-related AEs were comparable between keverprazan and lansoprazole.

2.
Clin Nutr ; 41(6): 1260-1271, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35504169

RESUMO

BACKGROUND & AIMS: Pro-inflammatory diet interacting with gut microbiome might trigger for Crohn's disease (CD). We aimed to investigate the relationship between dietary inflammatory potential and microflora/metabolites change and their link with CD. METHODS: The dietary inflammatory potential was assessed using a dietary inflammatory index (DII) based on the Food Frequency Questionnaire from 150 new-onset CD patients and 285 healthy controls (HCs). We selected 41 CD patients and 89 HCs who had not received medication for metagenomic and targeted metabolomic sequencing to profile their gut microbial composition as well as fecal and serum metabolites. DII scores were classified into quartiles to investigate associations among different variables. RESULTS: DII scores of CD patients were significantly higher than HCs (0.56 ± 1.20 vs 0.23 ± 1.02, p = 0.017). With adjustment for confounders, a higher DII score was significantly associated with higher risk of CD (OR: 1.420; 95% CI: 1.049, 1.923, p = 0.023). DII score also was positively correlated with disease activity (p = 0.001). Morganella morganii and Veillonella parvula were increased while Coprococcus eutactus was decreased in the pro-inflammatory diets group, as well as in CD. DII-related bacteria were associated with disease activity and inflammatory markers in CD patients. Among the metabolic change, pro-inflammatory diet induced metabolites change were largely involved in amino acid metabolic pathways that were also observed in CD. CONCLUSIONS: Pro-inflammatory diet might be associated with increased risk and disease activity of CD. Diet with high DII potentially involves in CD by mediating alterations in gut microbiota and metabolites.

3.
Gastroenterol Rep (Oxf) ; 10: goab056, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35382172

RESUMO

Background: Crohn's disease (CD) has a tendency for recurrence and requires adequate monitoring and personalized treatment. Since endoscopy is considerably invasive, serum biomarkers are required as alternatives for CD monitoring. Toward this, exosomal microRNAs (miRNAs) may serve as promising candidates. In this study, we aimed to assess the role of serum exosomal microRNA-144-3p (miR-144-3p) as a biomarker for CD monitoring. Methods: We prospectively recruited 154 patients without a history of surgery (Cohort 1) and 75 patients who were to undergo intestinal resection (Cohort 2). Serum samples were collected from Cohort 1 before colonoscopy and from Cohort 2 before surgery and during post-operative colonoscopic examination. The serum levels of exosomal miR-144-3p were measured using quantitative reverse-transcription polymerase chain reaction (PCR). Correlations between relative exosomal miR-144-3p levels, disease activity, and disease behavior were analysed. The area under the receiver-operating characteristic curve (AUC) was used to assess the predictive value of exosomal miR-144-3p regarding mucosal activity and post-operative recurrence. Results: A 3.33-fold increase in serum exosomal miR-144-3p levels was recorded in patients with CD compared with those in healthy controls (P < 0.001). The exosomal miR-144-3p levels were positively correlated with the simple endoscopic score of CD (ρ = 0.547, P < 0.001) as well as the Rutgeerts score (ρ = 0.478, P < 0.001). Elevated exosomal miR-144-3p levels were correlated with the penetrating disease with high specificity (100% [95% confidence interval, 95.1%-100%]). The accuracy of exosomal miR-144-3p for identifying post-operative recurrence was higher than that of C-reactive protein (CRP) (AUC, 0.775 vs 0.639; P < 0.001). Conclusions: Serum exosomal miR-144-3p is a reliable biomarker of mucosal inflammation and penetrating CD. It may identify endoscopic CD recurrence after intestinal resection with higher accuracy than CRP testing.

4.
J Inflamm Res ; 15: 2523-2537, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35479832

RESUMO

Background: Western-style diet (WSD) is associated with inflammatory bowel disease (IBD) prevalence. However, the impact of WSD on IBD development and its underlying mechanism remain unclear. Transcriptomics and metabolomics could be beneficial for identifying key factors in WSD-related experimental IBD susceptibility. However, no such study has been conducted yet. We aimed to analyze the implications of WSD for experimental colitis susceptibility in mice and its underlying mechanism using these high-throughput technologies. Methods: We fed experimental mice a WSD and a control diet from weaning. After 9 weeks, the mice were treated with 2,4,6 trinitrobenzene sulfonic acid to induce colitis, and the control group was treated with 50% ethanol (commonly used IBD animal model). Genome-wide microarray and liquid chromatography-tandem mass spectrometry were used to identify the differential transcripts and metabolites of experimental colitis with and without pre-illness WSD. Results: WSD induced more severe inflammation in experimental colitis than the control diet. We found 2540 up-regulated genes and 2737 down-regulated genes in experimental colitis with WSD compared with those for the control diet. In addition, levels of 41 colonic tissue metabolites and 56 serum metabolites showed significant differences. Integrating transcriptomic and metabolomic data, we found major co-expression networks through which WSD promoted experimental IBD susceptibility, including enzymes of biotransformation, glycan synthesis and metabolism, steroid hormone metabolites. Conclusion: Pre-illness WSD increased experimental colitis susceptibility. Our results could provide important evidences for the potential mechanisms and assist dietary recommendations to better manage IBD.

5.
Therap Adv Gastroenterol ; 15: 17562848221089096, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35399190

RESUMO

Background: Endoscopic recurrence is common in postoperative patients with Crohn's disease (CD). Monitoring endoscopic recurrence is important for selecting an appropriate treatment to prevent the development of postoperative disease. The aim of this study was to develop and validate a diagnostic model to identify endoscopic recurrence. Methods: This was a retrospective cohort study recruiting postoperative CD patients who underwent endoscopy at the First Affiliated Hospital, Sun Yat-sen University from January 2016 to June 2020. Endoscopic recurrence was defined as Rutgeerts score > i1. Thirty non-invasive biomarkers, including C-reactive protein, erythrocyte sedimentation rate, vitamin D, complete blood count, and biochemical blood indices, were used as candidate predictors to build a multivariate logistic regression diagnostic model. The predictive ability of the diagnostic models was assessed by receiving the area under the characteristic curve (AUC) and calibration plots, and internal validation was performed by the bootstrap method. Results: Two hundred and nineteen eligible patients were included in this study, and 135 (61.6%) patients had a postoperative endoscopic recurrence. The final diagnostic model included eight biomarkers with an AUC (95% confidence interval (CI)) of 0.796 (0.737-0.855) to identify endoscopic recurrence. The AUC, sensitivity, and specificity of this diagnostic model were 0.781 (0.780-0.782), 0.647 (0.643-0.651) and 0.811 (0.807-0.815), respectively, by internal validation. In addition, the diagnostic model exhibited good calibrability with calibration slope, calibration-in-the-large ('mean calibration') and Brier scores of 1.00, 0.00, and 0.175, respectively. Conclusion: This non-invasive biomarker-based diagnostic model has an excellent ability to identify endoscopic recurrence in patients with CD. Application of the model to clinical practice to monitor postoperative patients may be helpful for patient management.

7.
Cell Prolif ; : e13222, 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35373402

RESUMO

Inflammatory bowel disease (IBD) is a chronic recurrent gastrointestinal inflammatory disease that poses a heavy burden to the global healthcare system. However, the current paucity of mechanistic understanding of IBD pathogenesis hampers the development of aetiology-directed therapies. Novel therapeutic options based on IBD pathogenesis are urgently needed for attaining better long-term prognosis for IBD patients. The tripartite motif (TRIM) family is a large protein family including more than 70 structurally conservative members, typically characterized by their RBCC structure, which primarily function as E3 ubiquitin ligases in post-translational modification. They have emerged as regulators of a broad range of cellular mechanisms, including proliferation, differentiation, transcription and immune regulation. TRIM family proteins are involved in multiple diseases, such as viral infection, cancer and autoimmune disorders, including inflammatory bowel disease. This review provides a comprehensive perspective on TRIM proteins' involvement in the pathophysiology and progression of IBD, in particular, on intestinal mucosal barriers, gene susceptibility and opportunistic infections, thus providing novel therapeutic targets for this complicated disease. However, the exact mechanisms of TRIM proteins in IBD pathogenesis and IBD-related carcinogenesis are still unknown, and more studies are warranted to explore potential therapeutic targets of TRIM proteins in IBD.

8.
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
9.
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.

10.
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.

11.
Cancer Med ; 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35289113

RESUMO

OBJECTIVE: To evaluate the efficacy and outcome of transarterial embolization (TAE) plus octreotide long-acting repeatable (LAR) on patients with low-to-intermediate neuroendocrine tumor liver metastases (NETLM). METHODS: One hundred and sixteen patients with G1/G2 NETLM treated with TAE plus octreotide LAR at the First Affiliated Hospital, Sun Yat-sen University between January 12, 2016 and September 24, 2020 were reviewed. Radiological response was evaluated according to response evaluation criterion in solid tumor version 1.1. Overall progression-free survival (PFS) was assessed. Intrahepatic and extrahepatic PFS were evaluated in the whole cohort and in patients with the extrahepatic disease (EHD), respectively. Factors affecting treatment response and overall PFS were analyzed using the logistic regression model and Cox proportional hazard model. Adverse events were recorded and evaluated according to Common Terminology Criteria for Adverse Events 5.0. RESULTS: The median overall PFS of the whole cohort was 13.6 months. For the patients with EHD, the median intrahepatic PFS and extrahepatic PFS were 13.6 and 26.1 months, respectively. The median overall PFS of patients with hepatic tumor burden (HTB) <10%, 10%-25%, 25%-50%, and >50% were 25.2, 13.6, 11.2, and 12.3 months, respectively. Ki67 >10%, HTB >50%, and bone metastasis were independently associated with overall PFS. The objective response rate was 78.4%. In patients with HTB 25%-50% and >50%, responders (complete response or partial response) had significant prolonged PFS compared with nonresponders (stable disease or progression disease). Ki67 >10%, bone metastasis, and clear tumor margin were independently associated with response to TAE. The most frequent adverse events that occurred after TAE were postembolization syndrome, and no treatment-associated death occurred during the perioperative period. CONCLUSION: Transarterial embolization plus octreotide LAR can significantly prolong the PFS of neuroendocrine tumor liver metastases, especially with high HTB over 50%. Selected patients with HTB >25% (ki67 ≤10%, absence of bone metastasis, clear tumor margin) could derive prognostic advantage from the combined treatment.

12.
Cell Death Dis ; 13(2): 139, 2022 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-35145062

RESUMO

The exact pathogenesis of inflammatory bowel disease (IBD), a chronic gastrointestinal inflammatory disease comprising Crohn's disease and ulcerative colitis, remains unclear. Studies on ubiquitination, which regulates the degradation of inflammation signalling pathway molecules, and deubiquitination have provided novel insights. Targeting the ubiquitin-specific protease (USP) family of deubiquitinases elucidates IBD signalling pathway mechanisms and possibly, IBD therapeutic solutions. Here, we characterised USPs as chief regulators of pro-inflammatory signalling pathways, including nuclear factor-κB and transforming growth factor-ß; analysed the relationship between USPs and IBD pathogenesis in terms of genetic susceptibility, intestinal epithelial barrier, immunity, and gut microbiota; and discussed future research prospects.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Doença de Crohn/genética , Humanos , Doenças Inflamatórias Intestinais/patologia , Transdução de Sinais , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismo
13.
EBioMedicine ; 76: 103846, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35124427

RESUMO

BACKGROUND: Intestinal barrier impairment plays an essential role in the pathogenesis of Crohn's disease (CD), and claudins (CLDNs) dysfunction contributes to intestinal mucosa injury. SOX9, an important transcription factor, is upregulated in the disease-affected colon of patients with CD; however, its precise role in CD remains largely unknown. Our aim was to explore the interaction between SOX9 and CLDNs, and further elucidate the underlying mechanisms in CD. METHODS: SOX9 expression in patients with CD was evaluated using quantitative polymerase chain reaction, immunoblotting, and immunohistochemistry. The regulatory relationship between SOX9 and CLDNs was analyzed via a dual-luciferase reporter assay, chromatin immunoprecipitation, overexpression, and RNA interference methods. MicroRNAs (miRNAs) involved in the SOX9-CLDN pathway were predicted with bioinformatics analysis, and the upstream molecular mechanism was interpreted using MassARRAY methylation detection. FINDINGS: Upregulated expression of SOX9 in the disease-affected intestine mucosa was identified in both patients with CD and mice challenged with trinitrobenzene sulfonic acid (TNBS). SOX9 negatively regulated the expression of CLDN8, accompanying reduced intestinal permeability. MiR-145-5p downregulation was found in patients with CD and TNBS-induced colitis mice owing to an aberrant miR-145 promoter hypermethylation, which subsequently interfered the SOX9-CLDN8 pathway. MiR-145-5p agomir treatment alleviated TNBS-induced colitis in wild-type mice by inhibiting Sox9 expression and restoring Cldn8 expression, whereas similar findings were not apparent in the Cldn8-/- mice. INTERPRETATION: SOX9 mediates the crosstalk between upstream miR-145-5p and downstream CLDN8, and further impairs intestinal mucosal barrier homeostasis in CD. Targeting the miR-145-5p/SOX9/CLDN8 pathway represents a promising therapeutic strategy for CD. FUNDING: The National Natural Science Foundation of China (#81870374, #81670498, #81630018, #82070538, #8210031148), the Guangdong Science and Technology (#2017A030306021, #2020A1515111087), the Guangzhou Science and Technology Department (#202002030041), and the Fundamental Research Funds for the Central Universities (#19ykzd11).


Assuntos
Doença de Crohn , MicroRNAs , Animais , Claudinas/genética , Doença de Crohn/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Ácido Trinitrobenzenossulfônico/metabolismo , Ácido Trinitrobenzenossulfônico/toxicidade
14.
J Gastroenterol Hepatol ; 37(5): 812-822, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35088472

RESUMO

Esophageal ambulatory reflux monitoring is the current gold standard for the diagnosis of gastroesophageal reflux disease (GERD). In order to facilitate standardized procedure and improve diagnostic accuracy, clinical guidelines for ambulatory esophageal reflux monitoring were developed based on thorough literature search and working group conference by experts in gastrointestinal motility. Indications, contraindications, methodology, and reporting of ambulatory esophageal reflux monitoring were discussed in these clinical guidelines.


Assuntos
Esofagite Péptica , Refluxo Gastroesofágico , Adulto , China , Monitoramento do pH Esofágico/métodos , Refluxo Gastroesofágico/diagnóstico , Humanos , Manometria/métodos , Guias de Prática Clínica como Assunto
15.
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.

16.
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
17.
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
18.
Gut ; 71(2): 238-253, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34836916

RESUMO

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.


Assuntos
Saúde da Família , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori , Controle de Infecções/organização & administração , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , China , Consenso , Técnica Delfos , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/transmissão , Humanos , Lactente , Pessoa de Meia-Idade , Adulto Jovem
19.
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
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...