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BACKGROUND: Therapeutic monitoring of infliximab is limited by the time lag between drug-level measurement and dose adjustment, along with the cost of dose escalation. Strategies for dose reduction in stable patients on maintenance infliximab at supratherapeutic levels are uncertain. This study determined the feasibility of a pharmacist-driven strategy for immediate dose adjustment using a sliding scale at the point of care in stable patients with inflammatory bowel disease on maintenance therapy. METHODS: Adult patients with stable disease undergoing maintenance therapy with infliximab infusions, 5 mg/kg every 8 weeks, were prospectively studied. Trough drug levels were assessed by a rapid assay (and later by ELISA) at all infusions for up to 12 months with immediate but quantitatively small dose adjustment according to a sliding scale targeting a therapeutic range of 3-7 mcg/mL. Disease activity was assessed both clinically and biochemically. RESULTS: The rapid assay and ELISA detected similar infliximab levels, and the strategy added approximately 30 minutes to the duration of infusion events. Only 20% of 48 patients (77% with Crohn disease) had baseline trough infliximab concentrations within the therapeutic range. This value increased 3-fold after 24 and 48 weeks of interventions. One in 2 patients had baseline supratherapeutic levels, and most were brought into the therapeutic range without a discernible impact on disease activity by 1 dose adjustment, but 2 or 3 adjustments were generally needed for 29% of patients with subtherapeutic levels. Overall, drug costs were reduced by 4%. CONCLUSIONS: Immediate dose adjustment after infliximab rapid assay performed by a pharmacist using a sliding scale is a feasible strategy. Supratherapeutic infliximab levels can be safely and quickly brought into the therapeutic range using small dose adjustments without affecting disease activity, offsetting (at least partly) costs associated with dose escalation.
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Fármacos Gastrointestinais , Doenças Inflamatórias Intestinais , Adulto , Humanos , Infliximab/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Farmacêuticos , Sistemas Automatizados de Assistência Junto ao Leito , Doenças Inflamatórias Intestinais/tratamento farmacológico , Monitoramento de MedicamentosRESUMO
Cytomegalovirus (CMV) infection can be a challenging clinical problem in patients with inflammatory bowel disease (IBD), particularly ulcerative colitis. Clinical presentation is difficult to distinguish from an underlying disease flare. Several diagnostic modalities are now available and when combined can aid clinicians in the identification of patients who are most likely to benefit from antiviral therapy. The aim of this article is to review the available literature and outline a practical approach to the diagnosis and management of CMV in patients with IBD.
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Colite Ulcerativa , Infecções por Citomegalovirus , Doenças Inflamatórias Intestinais , Doença Crônica , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Citomegalovirus , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/terapia , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/terapiaRESUMO
BACKGROUND AND AIM: Limited data are available on the effects of fermentable fiber in altering intestinal pH and transit to predict efficacy-based delivery profiles of pH-dependent mesalamine coatings in ulcerative colitis (UC). This study aimed to examine regional pH and transit after acute changes in fermentable fiber intake in quiescent UC patients and their effects on drug release systems. METHODS: In a randomized, double-blind study, 18 patients with quiescent UC and 10 healthy controls were supplied meals high (13 g) or low (≤ 2 g) in fermentable fiber and subsequently ingested a wireless pH-motility capsule. After a ≥ 3-day washout, they crossed over to the other diet. Measurements of intestinal pH and transit were used to predict drug release for the various pH-dependent coatings. RESULTS: Increasing fermentable fiber intake lowered overall (median 6.2 [6.1-6.7] vs low: 6.9 [range or interquartile range: 6.4-7.4]; P = 0.01) and distal pH (7.8 [7.3-8.1] vs 8.2 [8.0-8.5]; P = 0.04) in controls. In UC patients, only cecal pH was decreased (high: 5.1 [4.8-5.5] vs low: 5.5 [5.3-5.7]; P < 0.01). Colonic transit in the UC cohort varied widely after a low-fiber intake but tended to normalize after the high fermentable fiber intake. Hypothetical coating dissolution profiles were heterogeneous in UC patients, with a multi-matrix delayed release system having the highest likelihood of patients (20-40%) with incomplete dissolution, and predominant small intestinal dissolution predicted for Eudragit L (94% patients) and S (44-69%). CONCLUSIONS: Patients with quiescent UC have abnormalities in intestinal pH and transit in response to acute changes in fermentable fiber intake. These have potentially detrimental effects on predicted luminal release patterns of pH-dependent 5-aminosalicylic acid release systems.
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Colite Ulcerativa/metabolismo , Fibras na Dieta/administração & dosagem , Fibras na Dieta/farmacologia , Liberação Controlada de Fármacos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Trânsito Gastrointestinal/efeitos dos fármacos , Mesalamina/metabolismo , Administração Oral , Adulto , Idoso , Feminino , Fermentação , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND & AIMS: Relatives of individuals with Crohn's disease (CD) carry CD-associated genetic variants and are often exposed to environmental factors that increase their risk for this disease. We aimed to estimate the utility of genotype, smoking status, family history, and biomarkers can calculate risk in asymptomatic first-degree relatives of patients with CD. METHODS: We recruited 480 healthy first-degree relatives (full siblings, offspring or parents) of patients with CD through the Guy's and St Thomas' NHS Foundation Trust and from members of Crohn's and Colitis, United Kingdom. DNA samples were genotyped using the Immunochip. We calculated a risk score for 454 participants, based on 72 genetic variants associated with CD, family history, and smoking history. Participants were assigned to highest and lowest risk score quartiles. We assessed pre-symptomatic inflammation by capsule endoscopy and measured 22 markers of inflammation in stool and serum samples (reference standard). Two machine-learning classifiers (elastic net and random forest) were used to assess the ability of the risk factors and biomarkers to identify participants with small intestinal inflammation in the same dataset. RESULTS: The machine-learning classifiers identified participants with pre-symptomatic intestinal inflammation: elastic net (area under the curve, 0.80; 95% CI, 0.62-0.98) and random forest (area under the curve, 0.87; 95% CI, 0.75-1.00). The elastic net method identified 3 variables that can be used to calculate odds for intestinal inflammation: combined family history of CD (odds ratio, 1.31), genetic risk score (odds ratio, 1.14), and fecal calprotectin (odds ratio, 1.04). These same 3 variables were among the 5 factors associated with intestinal inflammation in the random forest model. CONCLUSION: Using machine learning classifiers, we found that genetic variants associated with CD, family history, and fecal calprotectin together identify individuals with pre-symptomatic intestinal inflammation who are therefore at risk for CD. A tool for detecting people at risk for CD before they develop symptoms would help identify the individuals most likely to benefit from early intervention.
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Doença de Crohn , Biomarcadores , Doença de Crohn/genética , Fezes , Humanos , Inflamação , Intestino Delgado , Complexo Antígeno L1 Leucocitário , Índice de Gravidade de DoençaRESUMO
Evolution of treatment targets in IBD has increased the need for objective monitoring of disease activity to guide therapeutic strategy. Although mucosal healing is the current target of therapy in IBD, endoscopy is invasive, expensive and unappealing to patients. GI ultrasound (GIUS) represents a non-invasive modality to assess disease activity in IBD. It is accurate, cost-effective and reproducible. GIUS can be performed at the point of care without specific patient preparation so as to facilitate clinical decision-making. As compared with ileocolonoscopy and other imaging modalities (CT and MRI), GIUS is accurate in diagnosing IBD, detecting complications of disease including fistulae, strictures and abscesses, monitoring disease activity and detecting postoperative disease recurrence. International groups increasingly recognise GIUS as a valuable tool with paradigm-changing application in the management of IBD; however, uptake outside parts of continental Europe has been slow and GIUS is underused in many countries. The aim of this review is to present a pragmatic guide to the positioning of GIUS in IBD clinical practice, providing evidence for use, algorithms for integration into practice, training pathways and a strategic implementation framework.
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Trato Gastrointestinal/diagnóstico por imagem , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Ultrassonografia/métodos , Humanos , Monitorização Fisiológica/métodos , Sistemas Automatizados de Assistência Junto ao LeitoRESUMO
The contribution of rare coding sequence variants to genetic susceptibility in complex disorders is an important but unresolved question. Most studies thus far have investigated a limited number of genes from regions which contain common disease associated variants. Here we investigate this in inflammatory bowel disease by sequencing the exons and proximal promoters of 531 genes selected from both genome-wide association studies and pathway analysis in pooled DNA panels from 474 cases of Crohn's disease and 480 controls. 80 variants with evidence of association in the sequencing experiment or with potential functional significance were selected for follow up genotyping in 6,507 IBD cases and 3,064 population controls. The top 5 disease associated variants were genotyped in an extension panel of 3,662 IBD cases and 3,639 controls, and tested for association in a combined analysis of 10,147 IBD cases and 7,008 controls. A rare coding variant p.G454C in the BTNL2 gene within the major histocompatibility complex was significantly associated with increased risk for IBD (p = 9.65x10-10, OR = 2.3[95% CI = 1.75-3.04]), but was independent of the known common associated CD and UC variants at this locus. Rare (<1%) and low frequency (1-5%) variants in 3 additional genes showed suggestive association (p<0.005) with either an increased risk (ARIH2 c.338-6C>T) or decreased risk (IL12B p.V298F, and NICN p.H191R) of IBD. These results provide additional insights into the involvement of the inhibition of T cell activation in the development of both sub-phenotypes of inflammatory bowel disease. We suggest that although rare coding variants may make a modest overall contribution to complex disease susceptibility, they can inform our understanding of the molecular pathways that contribute to pathogenesis.
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Colite Ulcerativa/genética , Doença de Crohn/genética , Estudo de Associação Genômica Ampla , Glicoproteínas de Membrana/genética , Butirofilinas , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Doença de Crohn/imunologia , Doença de Crohn/patologia , Estudos de Associação Genética , Predisposição Genética para Doença , Antígenos HLA/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Abnormal handling of E. coli by lamina propria (LP) macrophages may contribute to Crohn's disease (CD) pathogenesis. We aimed to determine LP macrophage phenotypes in CD, ulcerative colitis (UC) and healthy controls (HC), and in CD, to compare macrophage phenotypes according to E. coli carriage. METHODS: Mucosal biopsies were taken from 35 patients with CD, 9 with UC and 18 HCs. Laser capture microdissection was used to isolate E. coli-laden and unladen LP macrophages from ileal or colonic biopsies. From these macrophages, mRNA was extracted and cytokine and activation marker expression measured using RT-qPCR. RESULTS: E. coli-laden LP macrophages were identified commonly in mucosal biopsies from CD patients (25/35, 71 %), rarely in UC (1/9, 11 %) and not at all in healthy controls (0/18). LP macrophage cytokine mRNA expression was greater in CD and UC than healthy controls. In CD, E. coli-laden macrophages expressed high IL-10 & CD163 and lower TNFα, IL-23 & iNOS irrespective of macroscopic inflammation. In inflamed tissue, E. coli-unladen macrophages expressed high TNFα, IL-23 & iNOS and lower IL-10 & CD163. In uninflamed tissue, unladen macrophages had low cytokine mRNA expression, closer to that of healthy controls. CONCLUSION: In CD, intra-macrophage E. coli are commonly found and LP macrophages express characteristic cytokine mRNA profiles according to E. coli carriage. Persistence of E. coli within LP macrophages may provide a stimulus for chronic inflammation.
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Doença de Crohn/imunologia , Escherichia coli/imunologia , Mucosa Intestinal/imunologia , Macrófagos/microbiologia , Fenótipo , Adulto , Idoso , Biomarcadores/metabolismo , Estudos de Casos e Controles , Colite Ulcerativa/imunologia , Colite Ulcerativa/microbiologia , Doença de Crohn/microbiologia , Citocinas/metabolismo , Escherichia coli/isolamento & purificação , Feminino , Humanos , Mucosa Intestinal/microbiologia , Macrófagos/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Crohn's disease (CD) is associated with intestinal dysbiosis, altered blood T cell populations, elevated faecal calprotectin (FC) and increased intestinal permeability (IP). CD-associated features present in siblings (increased risk of CD) but not in healthy controls, provide insight into early CD pathogenesis. We aimed to (1) Delineate the genetic, immune and microbiological profile of patients with CD, their siblings and controls and (2) Determine which factors discriminate between groups. DESIGN: Faecal microbiology was analysed by quantitative PCR targeting 16S ribosomal RNA, FC by ELISA, blood T cell phenotype by flow cytometry and IP by differential lactulose-rhamnose absorption in 22 patients with inactive CD, 21 of their healthy siblings and 25 controls. Subject's genotype relative risk was determined by Illumina Immuno BeadChip. RESULTS: Strikingly, siblings shared aspects of intestinal dysbiosis with patients with CD (lower concentrations of Faecalibacterium prausnitzii (p=0.048), Clostridia cluster IV (p=0.003) and Roseburia spp. (p=0.09) compared with controls). As in CD, siblings demonstrated a predominance of memory T cells (p=0.002) and elevated naïve CD4 T cell ß7 integrin expression (p=0.01) compared with controls. FC was elevated (>50â µg/g) in 8/21 (38%) siblings compared with 2/25 (8%) controls (p=0.028); whereas IP did not differ between siblings and controls. Discriminant function analysis determined that combinations of these factors significantly discriminated between groups (χ(2)=80.4, df=20, p<0.001). Siblings were separated from controls by immunological and microbiological variables. CONCLUSIONS: Healthy siblings of patients with CD manifest immune and microbiological abnormalities associated with CD distinct from their genotype-related risk and provide an excellent model in which to investigate early CD pathogenesis.
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Doença de Crohn/imunologia , Doença de Crohn/microbiologia , Disbiose/imunologia , Disbiose/microbiologia , Mucosa Intestinal/microbiologia , Microbiota , Linfócitos T/imunologia , Adolescente , Adulto , Ensaio de Imunoadsorção Enzimática , Fezes/microbiologia , Feminino , Genótipo , Humanos , Imunofenotipagem , Masculino , Irmãos , Reino Unido , Adulto JovemRESUMO
BACKGROUND: The aims of this study were to develop and evaluate a high/low-emulsifier diet and compare emulsifier content with preclinical studies that have associated Crohn's disease with emulsifiers. METHODS: Supermarkets were audited with a seven-day high- (HED) and low-emulsifier diet (LED) meal plan developed. The emulsifier content of food was sought from food manufacturers, compared to acceptable daily intake (ADI), and doses were provided in trials. Nutritional composition analysis was completed. Healthy adults ate these diets for seven days in a randomized single-blinded cross-over feeding study to assess palatability, tolerability, satiety, food variety, dietary adherence, blinding and the ease of following the meal plan via visual analogue scale. RESULTS: A database of 1680 foods was created. There was no difference in nutritional content between the HED and LED, except HED had a higher ultra-processed food content (p < 0.001). The HED contained 41 emulsifiers, with 53% of the products able to be quantified for emulsifiers (2.8 g/d), which did not exceed the ADI, was similar to that in observational studies, and was exceeded by doses used in experimental studies. In ten participants, diets were rated similarly in palatability-HED mean 62 (5% CI 37-86) mm vs. LED 68 (54-82) mm-in tolerability-HED 41 (20-61) mm vs. LED 55 (37-73) mm-and in satiety HED 57 (32-81) mm vs. LED 49 (24-73) mm. The combined diets were easy to follow (82 (67-97) mm) with good variety (65 (47-81)) and excellent adherence. CONCLUSION: Nutritionally well-matched HED and LED were successfully developed, palatable and well tolerated.
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Doença de Crohn , Estudos Cross-Over , Emulsificantes , Humanos , Adulto , Masculino , Feminino , Doença de Crohn/dietoterapia , Austrália , Pessoa de Meia-Idade , Abastecimento de Alimentos , Método Simples-Cego , Adulto Jovem , Valor Nutritivo , Dieta , SupermercadosRESUMO
BACKGROUND: Although dietary emulsifiers are implicated in the pathogenesis of Crohn's disease, their effect has not been studied in humans. AIM: To determine the effects of high- and low-emulsifier diets (HED, LED) on intestinal barrier function in healthy subjects in unstressed and acutely stressed states. METHODS: We conducted a single-blinded, cross-over, controlled feeding trial in 22 healthy adults. After recording 7 days of their habitual diet, we randomised participants to HED or LED with ≥3-week washout between diets. On dietary completion, acute stress was induced via intravenous corticotrophin-releasing hormone. We assessed dietary adherence, effects on 2-h urinary lactulose: rhamnose ratio (LRR), serum concentrations of lipopolysaccharide-binding protein, soluble-CD14 and markers of epithelial injury and inflammation. RESULTS: Dietary adherence was excellent. In an unstressed state, median (interquartile range) LRR during HED was 0.030 (0.018-0.042); on LED, this was 0.042 (0.029-0.078; p = 0.04). LPB concentrations were lower on HED than LED (p = 0.026), but no differences were observed for epithelial injury or inflammation. Under acute stress, LRR increased by 89% (-1% to 486%) on HED (p = 0.004), differing (p = 0.001) from 39% (1%-90%) decrease on LED (p = 0.009). Soluble-CD14 also increased (p < 0.001). The LED had a prolonged carry-over effect on suppressing HED-induced changes during stress. Similar changes in LRR and soluble-CD14 were observed when HED was used as the first diet (both p < 0.01). CONCLUSION: High intake of emulsifiers improved barrier function in the unstressed state, but increased intestinal permeability to stress, without evidence of inflammation. A LED was protective of the stress effect.
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OBJECTIVE: Foreign body ingestion (FBI) occurs infrequently but can be associated with rare risks including perforation. There is limited understanding of the impact of adult FBI in Australia. We aim to evaluate patient characteristics, outcomes and hospital costs of FBI. DESIGN: A retrospective cohort study of patients with FBI was performed at a non-prison referral centre in Melbourne, Australia. International Classification of Disease-10 coding identified patients with gastrointestinal FBI over financial years 2018-2021. Exclusion criteria were food bolus, medication foreign body, object in anus or rectum, or non-ingestion. Criteria for 'emergent' classification were oesophagus, size >6 cm, disc batteries, airway compromise, peritonitis, sepsis and/or suspected viscus perforation. RESULTS: Thirty-two admissions attributed to 26 patients were included. The median age was 36 years (IQR: 27-56), 58% were male and 35% had a prior psychiatric or autism spectrum disorder. There were no deaths, perforations or surgery. Gastroscopy was performed in 16 admissions and 1 was scheduled following discharge. Rat-tooth forceps were used in 31% and an overtube was used in 3 cases. The median time from presentation to gastroscopy was 673 minutes (IQR: 380-1013). Management was adherent to European Society of Gastrointestinal Endoscopy guidelines in 81%. After excluding admissions with FBI as a secondary diagnosis, median admission cost was $A1989 (IQR: $A643-$A4976) and total admission costs over the 3 years was $A84 448. CONCLUSION: FBI in an Australian, non-prison referral centre is infrequent, can often be safely managed expectantly, and has limited impact on healthcare utilisation. Early, outpatient endoscopy could be considered for non-urgent cases, which may reduce costs while maintaining safety.
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Transtorno do Espectro Autista , Corpos Estranhos , Masculino , Humanos , Feminino , Custos Hospitalares , Estudos Retrospectivos , Transtorno do Espectro Autista/complicações , Austrália/epidemiologia , Endoscopia Gastrointestinal , Corpos Estranhos/epidemiologia , Corpos Estranhos/complicações , Corpos Estranhos/diagnóstico , Hospitais , Custos de Cuidados de Saúde , Encaminhamento e ConsultaRESUMO
BACKGROUND: Exclusive enteral nutrition (EEN) induces remission and mucosal healing in patients with Crohn's disease, but the mechanism of action remains unknown. AIM: To outline current understanding of the mechanisms of action of EEN. METHODS: From a comprehensive literature search, published data were critically examined in a narrative review. RESULTS: Multiple potential mechanisms of action have been identified. EEN optimises nutritional status. Differences in gut microbiota in terms of overall diversity and taxonomic community structure are observed between responders and non-responders to EEN. Therapy with EEN alters microbial metabolites (including faecal short-chain fatty acids, amino acids, branched-chain amino acids and sulphide) and faecal pH. Epithelial effects and restoration of barrier function, as well as changes in mucosal cytokine profiles and T-cell subsets are observed in responders to EEN. The impact of inclusion or exclusion of specific dietary components may be of importance, but putative detrimental components are found in many formulas. A major challenge in interpreting these findings is that they often contradict or change in opposite directions to what is considered 'beneficial'. It is difficult to differentiate between the observations following EEN being driven by EEN per se and those associated with resolving inflammation. CONCLUSIONS: The mechanisms of action of EEN are likely to involve a complex interplay between host mucosal immune response and luminal environment, but the identity of key factors remains poorly understood. A better definition of pathogenic factors may aid in developing more targeted dietary treatment and provide insights into the pathogenesis of Crohn's disease.
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Doença de Crohn , Humanos , Doença de Crohn/terapia , Nutrição Enteral , Fezes , Mucosa , Dieta , Indução de RemissãoRESUMO
Objective: To evaluate clinical outcomes, patterns of use, tolerance and nutritional outcomes of exclusive enteral nutrition (EEN) in adults with Crohn's disease and to compare initiation in the inpatient compared with ambulatory care setting. Design/method: Adults with Crohn's disease who received EEN at a single centre over 2.5 years were identified and outcomes assessed via examination of patient records. Results: EEN was initiated in 60 patients (23 as an outpatient) who had objective evidence of active disease. Of 49 in whom the goal was induction of remission, 28 completed EEN and 24 achieved clinical remission/response. Twenty-one withdrew prematurely, due to intolerance in 15 and disease factors in 6. Of 11 with a planned intervention, 6 fulfilled the goal of downstaging disease while two were intolerant. Completion of the prescribed therapy was associated with self-reported adherence to EEN and with improvements in disease activity scores and biochemical markers. Malnutrition halved (40% to 20%) and intentional weight loss (median 5.1 kg) was achieved in six obese patients. The major reason for intolerance was the inability to accept total avoidance of non-formula food. There were no differences in any outcomes according to the location of initiation of therapy. Conclusion: Positive outcomes occur in 70% of adult patients with Crohn's disease tolerating EEN and 81% in those who are able to completely adhere to EEN, without compromise of nutritional status. Similar success occurs when initiated as an inpatient or outpatient. Failure to tolerate EEN is the major hurdle to its use.
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Background and Aim: Nonspecific ileitis is inflammation of the ileum without specific diagnostic features. A minority may go on to develop Crohn's disease, but optimal pathways of further investigation have not been established. This study aimed to identify a cohort of patients with nonspecific ileitis and to determine the value of ileal histology and gastrointestinal ultrasound in identifying/excluding Crohn's disease. Patients and Methods: In a retrospective analysis, all patients having nonspecific ileitis at colonoscopy from January 2010 to August 2021 were identified. Clinical associations with those subsequently diagnosed with Crohn's disease were examined with specific reference to ileal histology and gastrointestinal ultrasound. Results: Of 29 638 procedures, 147 patients (0.5%) had nonspecific ileitis. Crohn's disease was subsequently diagnosed in 8 patients (5.4%) at a median of 148 (range 27-603) days after colonoscopy. The presence of chronic inflammation on ileal biopsies was more common in those subsequently diagnosed with Crohn's disease (63% vs 20%; P = 0.0145). On gastrointestinal ultrasound, none of the 26 patients with normal bowel wall thickness (<3 mm) were subsequently diagnosed with Crohn's disease, and repeat ultrasound in 15 patients 1 year later showed no change. Of the nine patients with abnormal sonographic findings, three were diagnostic for Crohn's disease. Repeat ultrasound revealed Crohn's disease in two, while four had resolution of the abnormal findings. Conclusion: Although ileal histology was of limited value in identifying patients with nonspecific ileitis who were subsequently diagnosed with Crohn's disease, gastrointestinal ultrasound was highly informative. Prospective studies are needed to confirm the value of gastrointestinal ultrasound as a diagnostic and monitoring tool in this setting.
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OBJECTIVE: Gastrointestinal ultrasound (GIUS) accurately assesses inflammation and is responsive to changes in inflammatory bowel disease. This study aimed to determine the prognostic utility of sonographic response in the first 14 weeks of a newly-instituted therapy with therapeutic response at 46 weeks and to compare its performance with standard clinical assessment tools. METHODS: Patients with sonographic evidence of inflammation were assessed by GIUS, clinical activity, serum C-reactive protein and faecal calprotectin again 2, 6 and 14 weeks after commencing a new biologic or thiopurine. Treatment failure was defined as undergoing surgery, hospitalisation, escalation of dosage or introduction of new medication over 46-weeks' follow-up. Sonographic response was defined as a decrease in bowel wall thickness and improved vascularity. RESULTS: In 31 patients (median age 49 years, 74% Crohn's disease), sonographic response at 14 weeks [OR 19.3, 95% confidence interval (CI), 3.23-101.10; P = 0.0054] and faecal calprotectin (P = 0.018), but no clinical disease activity or C-reactive protein, were predictive of subsequent treatment response. Sonographic response alone was predictive at week 6 (P = 0.016), but not week 2. 16% reduction in bowel wall thickness at 6 weeks (area-under-the-receiver-operator-curve=0.86; P = 0.002; sensitivity 72%, specificity 90%), with similar performance for 10% at 14 weeks, was associated with treatment response. CONCLUSION: Sonographic response as early as 6 weeks after initiation of a new therapy may accurately predict treatment outcomes over 46 weeks and is superior to other markers used to monitor disease activity.
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Doença de Crohn , Doenças Inflamatórias Intestinais , Proteína C-Reativa/análise , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/tratamento farmacológico , Fezes/química , Humanos , Inflamação , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Complexo Antígeno L1 Leucocitário , Pessoa de Meia-IdadeRESUMO
SCOPE: The concept that dietary factors are key risk and preventive agents in the development of Crohn's disease (CD), while widely believed and supported by epidemiological evidence, has yet to lead to clear identification of those factors through clinical trials. The aims are to examine the strength of the epidemiological evidence of diet and its association with CD, examine how interpretation of mostly epidemiological data has shaped ideas for potential dietary therapies, and to explore other factors that have driven the design of dietary clinical trials in CD. METHODS: A literature search is performed in PubMed, Medline, EMBASE, and Google Scholar for prospective cohort studies and randomized clinical trials (RCTs) using search terms-"Crohn's disease," "diet," "risk," "remission," "treat," "cohort," "randomised." RESULTS: Only four prospective cohort studies examine the relationship of diet and CD development, but these trials have been largely ignored by dietary RCTs in CD, which have used predominantly exclusion diets in small populations without objective endpoint assessment. Only one demonstrated clinical benefit to intestinal inflammation. CONCLUSION: Investment in large multicenter dietary clinical trials that focus on dietary inclusions with objective endpoint assessment are needed to provide safe, sustainable dietary therapy to patients with CD.
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Doença de Crohn/dietoterapia , Doença de Crohn/epidemiologia , Ensaios Clínicos como Assunto , Humanos , Estudos ProspectivosRESUMO
OBJECTIVE: Gastrointestinal ultrasound is a radiological investigation for monitoring patients with inflammatory bowel disease. However, the reliability of the findings depends on the reproducibility of results between different operators. Thus, the study aim was to assess the interrater reliability of gastrointestinal ultrasound in individuals with inflammatory bowel disease between gastroenterologists with varying GIUS experience. . METHODS: Patients were prospectively recruited at the commencement of a new medical therapy for a baseline assessment, with a second assessment at the end of treatment induction (3 months). Consecutive, blinded ultrasounds were performed by two operators for every test. Gastrointestinal ultrasound examination included assessment of bowel wall thickness, vascularity, wall stratification assessment, mesenteric hyperechogenicity and lymphadenopathy. RESULTS: Forty-nine patients were recruited (Crohn's n = 27, ulcerative colitis n = 22) with 35 returning for a repeat assessment at 3 months. At baseline, the intraclass coefficient for bowel wall thickness was near perfect (0.882). By bowel segment, the closest correlation was in the terminal ileum and differences in bowel wall thickness were similar by disease subtype. All other ultrasound indices of disease activity demonstrated substantial to near-perfect agreement with Gwet's agreement coefficient: vascularity (0.681), wall stratification (0.685), mesenteric hyperechogenicity (0.841) and lymphadenopathy (0.633). Similar findings were seen at 3 months. CONCLUSION: There is substantial agreement between operators of varying experience in gastrointestinal ultrasound findings in patients with Crohn's disease or ulcerative colitis and this is repeatedly demonstrated over time. Thus, a well-trained operator should be sufficient to assess disease activity in patients with inflammatory bowel disease.
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Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Colite Ulcerativa/diagnóstico por imagem , Doença de Crohn/diagnóstico por imagem , Humanos , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Estudos Prospectivos , Reprodutibilidade dos Testes , UltrassonografiaRESUMO
Approximately 30% of patients hospitalised with severe ulcerative colitis do not respond to corticosteroids, but the decision to introduce salvage therapy is delayed to at least the third day of treatment, according to the widely applied Oxford criteria to assess response. This pilot study aimed to determine if gastrointestinal ultrasound performed on admission can predict steroid-refractory disease. In 10 consecutive patients with severe ulcerative colitis, gastrointestinal ultrasound was performed within 24 h of admission. Six patients failed corticosteroids and required infliximab salvage therapy. Colonic bowel wall thickness was a median of 4.6 mm (range 4.2-5.6 mm) in those responding to steroids compared with 6.2 mm (6-7.9 mm) in those requiring salvage therapy (pâ¯=â¯0.009). Any colonic segment with a bowel wall thickness of >6 mm was associated with the need for salvage therapy (pâ¯=â¯0.033). Gastrointestinal ultrasound may provide an early indication of poor corticosteroid response and enable a timelier introduction of salvage therapy in patients with severe ulcerative colitis.
Assuntos
Colite Ulcerativa/diagnóstico por imagem , Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Infliximab/uso terapêutico , Ultrassonografia , Corticosteroides/uso terapêutico , Adulto , Colo/diagnóstico por imagem , Feminino , Hospitalização , Humanos , Masculino , Seleção de Pacientes , Projetos Piloto , Valor Preditivo dos Testes , Terapia de Salvação , Exacerbação dos Sintomas , Fatores de Tempo , Falha de Tratamento , Adulto JovemRESUMO
BACKGROUND: Intestinal ultrasound (IUS) is a valuable tool for assessment of Crohn's disease (CD). However, there is no widely accepted luminal disease activity index. AIMS: To identify appropriate IUS protocols, indices, items, and scoring methods for measurement of luminal CD activity and integration of IUS in CD clinical trials. METHODS: An expert international panel of adult and paediatric gastroenterologists (n = 15) and radiologists (n = 3) rated the appropriateness of 120 statements derived from literature review and expert opinion (scale of 1-9) using modified RAND/UCLA methodology. Median panel scores of 1 to ≤3.5, >3.5 to <6.5 and ≥6.5 to 9 were considered inappropriate, uncertain and appropriate ratings respectively. The statement list and survey results were discussed prior to voting. RESULTS: A total of 91 statements were rated appropriate with agreement after two rounds of voting. Items considered appropriate measures of disease activity were bowel wall thickness (BWT), vascularity, stratification and mesenteric inflammatory fat. There was uncertainty if any of the existing IUS disease activity indices were appropriate for use in CD clinical trials. Appropriate trial applications for IUS included patient recruitment qualification when diseased segments cannot be adequately assessed by ileocolonoscopy and screening for exclusionary complications. At outcome assessment, remission endpoints including BWT and vascularity, with or without mesenteric inflammatory fat, were considered appropriate. Components of an ideal IUS disease activity index were identified based upon panel discussions. CONCLUSIONS: The panel identified appropriate component items and applications of IUS for CD clinical trials. Empiric evidence, and development and validation of an IUS disease activity index are needed.