Summary
Background
Conflicting results have been recently reported for the accuracy of the Endoscopic Reference Score (EREFS), an standardised endoscopic classification, to predict the histological ...activity of eosinophilic oesophagitis (EoE).
Aim
To evaluate the accuracy of the EREFS to predict either histological or clinical activity of EoE.
Methods
Prospective multicentre study conducted in eight Spanish centres evaluating adult EoE patients, either naïve or after treatment. Symptoms were evaluated before upper endoscopy through the Dysphagia Symptom Score, whereas researchers scored the EREFS immediately after the endoscopic procedure, unaware of the histological outcome.
Results
One hundred and forty‐five EoE patients undergoing 240 consecutive endoscopic procedures were included. Exudates (P = 0.03), furrows (P = 0.03) and a composite score of inflammatory signs (exudates, furrows and oedema) (P < 0.001) accurately predicted histological activity. Exudates were the only endoscopic sign showing a good correlation with histological outcome after therapy. Furrows and oedema persisted in 50% and 70% of patients despite histological remission. No endoscopic feature exceeded 70% accuracy to predict histological activity. Likewise, no endoscopic finding could adequately predict dysphagia severity. Crepe paper mucosa, diffuse exudates and severe rings correlated with higher symptom scores.
Conclusions
Endoscopic findings assessed by the Endoscopic Reference Score did not correlate with histological or clinical disease activity in adult EoE patients. Only exudates correlated with peak eosinophil count and histological outcome, whereas furrows and oedema persisted in over half of patients despite histological remission.
Abstract
Background
Ustekinumab (UST) is usually employed in Crohn’s disease (CD) after anti-tumor necrosis factor (TNF) therapy failure or if anti-TNF therapy is contraindicated. Higher UST trough ...levels have been associated with better clinical/endoscopic outcomes, so dose escalation (reducing dosing intervals or reinduction) is widely used. Intravenous (iv) maintenance has been proposed, but it has been barely assessed.
Methods
Single center, retrospective case series. All patients with CD starting treatment with UST and receiving at least one dose were eligible. Subjects started on UST in other centers or those prescribed for any indication different than IBD were excluded.
Dose escalation to iv maintenance was performed in case of lack or loss of response or persisting significant inflammation in laboratory tests, imaging or endoscopy. Following dose escalation, Harvey Bradshaw Index (HBI), fecal calprotectin and C reactive protein (CRP) were checked at each visit. UST trough levels were also assessed.
Primary outcomes were clinical remission (HBI<5) and biochemical remission (fecal calprotectin <250 mg/kg). Adverse events, and treatment persistence were also assessed.
Results
A total of 131 patients treated between May 2017 and August 2023 were included. Sixty (45.8%) patients were escalated to iv UST maintenance after a median of 14.1 (IQR: 8-50.4) weeks of UST treatment. Baseline characteristics are shown in table 1.
Patients were started on iv UST maintenance due to persistent inflammatory activity in imaging/endoscopic procedures in 21 (35%), clinical response without remission in 17 (28.3%), low trough concentrations in 16 (26.7%) and primary non-response in 6 (10%). Thirty-three (55%) were receiving sc UST every 4 weeks and 23 (38.3%) started iv maintenance directly after UST induction. At initiation of iv maintenance, patients presented a median HBI index of 4 (IQR: 2-7), a fecal calprotectin of 514 (IQR: 213-1078) mg/kg and UST trough levels of 4.8 (IQR: 3-7.3) μg/mL.
Following iv maintenance, UST trough levels increased to 10.9 (IQR: 8-17.4). Clinical remission rates increased from baseline (48.3%) at weeks 8 (79.6%, p=0.001), 24 (72%, p=0.01) and 48 (74.4%, p=0.01). However, the 10-13% increase observed in the biochemical remission rates was not statistically significant (figure 1). Treatment persistence 2 years after starting UST iv maintenance was 72.2% (95% CI: 54.7-83.8%). Only 2 infectious adverse events were observed in the whole cohort (2/131, 1.6%), both in patients receiving sc maintenance.
Conclusion
UST iv maintenance in bio-experienced patients is safe and increases clinical remission rates, although it did not achieve a relevant improvement in biochemical remission rates.
Abstract
Background
Inflammatory bowel diseases (IBD), comprising Crohn´s disease (CD) and ulcerative colitis (UC), are characterised by chronic, relapsing and remitting inflammation of the ...gastrointestinal tract. Despite significant efforts to understand the pathogenetic mechanisms of IBD, the elucidation of its etiopathology and progression remains incomplete. This study aimed to clarify IBD pathogenesis using a multiomic approach in serum, urine, intestinal tissue and stool samples.
Methods
We performed a multiomic analysis (transcriptomic, proteomic, metabolomic and metagenomic) in a discovery cohort of 53 patients with active CD, 50 patients with active UC, and 33 healthy controls (HC). Proteomic analysis of intestinal tissue was performed by liquid chromatography-mass spectrometry, serum and urine samples were used for metabolome study using nuclear magnetic resonance spectroscopy, and metagenomic analysis of stool samples was performed by 16rRNA gene sequencing.
Results
Gene expression profiles showed a detailed transcriptome landscape of intestinal tissue in patients with CD and UC. A total of 4,105 proteins were identified in mucosal biopsies, of which 2,128 were differentially expressed (DE) between CD and HC, 2,715 proteins DE in UC compared with HC, and 1,653 proteins DE between CD and UC. Metabolomic analyses revealed metabolites and pathways related to ketone, amino sugar and methyl histidine metabolism, Warburg effect, and ammonia recycling deregulated in IBD patients. Moreover, metagenomic results indicated that CD and UC differ in their microbial populations according to beta diversity. In comparison to HC, the microbial population in CD was different, and its alpha diversity was significantly lower (Figure 1).
Conclusion
The results showed that some analytes identified could play essential roles in the pathogenesis of CD and UC. New potential key mechanisms that could help to understand the information of omics layers that underlies the pathogenesis of IBD have been outlined.
Background:
Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost ...considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1 year in patients who discontinue anti-TNF treatment versus those who continue treatment.
Methods:
This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn’s disease or ulcerative colitis who have achieved clinical remission for ⩾6 months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1 year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal.
Results:
Enrolment began in 2016, and the study is expected to end in 2020.
Conclusions:
This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission.
Clinical trial reference number:
EudraCT 2015-001410-10
Extraintestinal respiratory manifestations in inflammatory bowel disease (IBD) are rare. We present a case of bronchiolitis obliterans organizing pneumonia (BOOP) in a patient with Crohn s disease, ...with clinical remission with no drug therapy.
Introducción:
El adenocarcinoma gástrico (ADG) es uno de los tumores gastrointestinales más frecuentes. El estadiaje prequirúrgico locorregional es esencial para individualizar el tratamiento, pues ...se recomienda valorar neoadyuvancia en estadios localmente avanzados (T3-T4 y N+). La ecoendoscopia (USE) y la Tomografía computarizada (TC) son dos técnicas utilizadas en el estudio de extensión locorregional, sin embargo hay pocos trabajos que comparen su rentabilidad diagnóstica.
Objetivo:
Comparar la rentabilidad diagnóstica de la USE y el TC en el estadiaje prequirúrgico locorregional del ADG.
Material y Métodos:
Estudio retrospectivo comparativo incluyendo los pacientes intervenidos de ADG entre Enero 2012 y Enero 2016 con estadiaje prequirúrgico mediante TC y USE. Se empleó ecoendoscopio radial Olympus GF-UMQ 130, con frecuencias entre 7.5 y 12 MHz. Se compararon los hallazgos del TC y USE con el resultado de la pieza quirúrgica. Los pacientes con neoadyuvancia fueron excluidos.
Resultados:
42 pacientes incluidos, 62% varones. Entre 10 pacientes en estadio local precoz (T1-T2), 80% (8) fueron diagnosticados adecuadamente mediante USE y TC. Entre 32 pacientes en estadio local avanzado (T3-T4), 84% (27) fueron diagnosticados adecuadamente mediante USE y 55% (19) mediante TC. En el diagnóstico de estadios avanzados, la sensibilidad (S) y la especificidad (E) de la USE fue 84 y 80% respectivamente
versus
59% y 80% de S y E por TC respectivamente. Entre 11 pacientes N0, 73% (8) fueron identificados adecuadamente por USE y 64% (7) por TC. Entre 31 pacientes N+, 29% (9) fueron identificados adecuadamente por USE y 55% (17) por TC. La S y E de la USE en el estadiaje ganglionar fue 29% y 73% respectivamente; la S y E del TC fue 55% y 63% respectivamente.
Conclusiones:
La USE presenta mayor sensibilidad que el TC en el diagnóstico de estadios localmente avanzados de ADG (infiltración mural “T”) y permite discriminar mejor este grupo de pacientes potencialmente subsidiario de tratamiento neoadyuvante.
Las manifestaciones extraintestinales respiratorias en la enfermedad inflamatoria intestinal (EII) son excepcionales. Presentamos un caso de bronquiolitis obliterante con neumonía organizada (BONO) ...en paciente con enfermedad de Crohn, en remisión clínica sin tratamientos farmacológicos.
Abstract
Background
It has been reported that familial aggregation occurs in 10–20% of inflammatory bowel disease (IBD) patients1. Familial IBD has been associated with disease anticipation2 and with ...an increased need for immunosuppressants3 and surgery4. However, most studies were performed before the widespread use of biological agents and this may impact on the need for surgery.
We aimed to compare the clinical outcomes of IBD (by means of the need for biological therapy and abdominal surgery) between familial and sporadic forms of IBD in the era of biological therapies.
Methods
Data were extracted from the ENEIDA registry by GETECCU, a Spanish, prospectively-maintained, IBD database in which more than 80 centers are participating.
Only adult patients diagnosed with IBD since 2005 and prospectively followed in the registry since diagnosis were included.
Familial IBD was defined as those cases with at least one first-degree relative diagnosed with IBD. Sporadic IBD was defined as those cases with no familial relative (of any degree) with IBD.
Kaplan-Meier survival curves were performed to evaluate the cumulative probabilities of remaining biologic-free and surgery-free. Log-rank test was performed to compare them between familial and sporadic IBD forms. Chi-square test was performed for the rest of variables.
Results
A total of 5,263 patients (2,627 Crohn’s disease CD; 2,636 ulcerative colitis UC) were included. Of them, 507 (10%) were familial cases (274 CD, 233 UC; P=0.05). The median follow-up was 38,4 and 35.5 months, respectively (P=0.086).
Familial cases were younger (P=0.022) and had a higher proportion of females among UC cases (P=0.048).
No differences were observed in the need for biological therapy in both CD and UC between familial and sporadic IBD. Regarding surgery, no differences were observed in the cumulative probabilities of a first intestinal resection for CD and colectomy for UC. Similar results were obtained when all the analyses were restricted to those subgroups at high-risk for surgery (i.e. CD with ileal involvement and extensive UC).
Conclusion
In patients diagnosed with IBD in the era of biological therapies, familial forms have the same requirements for biological agents and resectional surgery as sporadic forms. Therefore, familial aggregation does not seem to be a factor for a more aggressive disease.
Introducción:
El acceso por USE a la vía biliar permite el drenaje paliativo en la obstrucción neoplásica tras CPRE fallida. La experiencia preliminar con la HGE como alternativa a la vía percutánea ...para drenaje biliar en pacientes con derivaciones biliodigestivas y estenosis anastomótica o coledocolitiasis, y en pacientes con transección biliar completa, es ambigua.
Objetivo:
Evaluar la viabilidad de la HGE mediante PMC transmurales como método de drenaje y puerta de entrada para terapéutica biliar guiada por radiología o colangioscopia transhepática en pacientes con anatomía compleja. Análisis de tendencias evolutivas.
Material y método:
Revisión 18 pacientes (9 varones; 66.5 47–91 años) en los que se practicó HGE mediante PMC como ruta de intervención y drenaje biliar intercurrente. Se comparan un periodo inicial (jun 2006- jul 2011) y posterior (8/2011–7/2012) en cuanto a indicación, técnica, complicaciones, intervenciones y éxito terapéutico final.
Resultados:
Se planteó HGE temporal en 9 pacientes de cada periodo (Tabla), tras excluir 3 del inicial (2 sin diana para punción; 1 sin datos evolutivos) y 1 del posterior (pendiente de intervención a través de la PMC). La proporción litiasis (hepatolitiásis)/estenosis (transección) fue similar en ambos periodos. Solo un caso de cada grupo tuvo una HGE temporal para drenaje sin intervencionismo asociado. La PMC se pudo retirar en todos los 15 casos restantes, pero la carga terapéutica (número de sesiones), la incidencia de complicaciones, y el tiempo de permanencia de la HGE fueron mayores en el periodo inicial. La tasa de éxito terapéutico final (extracción de las litiasis y/o canalización de las estenosis/transección) fue mayor en el periodo posterior.
Conclusiones:
Estos datos muestran un uso cada vez más frecuente y eficaz de la HGE temporal en pacientes biliares no susceptibles de solución endoscópica convencional. Pueden evitarse así hepatectomías o derivaciones biliares, aunque este nuevo abordaje endoscópico sigue resultando gravoso.
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