Genetic Variants Associated with Biological Treatment Response in Inflammatory Bowel Disease: A Systematic Review.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the digestive tract usually characterized by diarrhea, rectal bleeding, and abdominal pain. IBD includes Crohn's disease and ulcerative colitis as the main entities. IBD is a debilitating condition that can lead to life-threatening complications, involving possible malignancy and surgery. The available therapies aim to achieve long-term remission and prevent disease progression. Biologics are bioengineered therapeutic drugs that mainly target proteins. Although they have revolutionized the treatment of IBD, their potential therapeutic benefits are limited due to large interindividual variability in clinical response in terms of efficacy and toxicity, resulting in high rates of long-term therapeutic failure. It is therefore important to find biomarkers that provide tailor-made treatment strategies that allow for patient stratification to maximize treatment benefits and minimize adverse events. Pharmacogenetics has the potential to optimize biologics selection in IBD by identifying genetic variants, specifically single nucleotide polymorphisms (SNPs), which are the underlying factors associated with an individual's drug response. This review analyzes the current knowledge of genetic variants associated with biological agent response (infliximab, adalimumab, ustekinumab, and vedolizumab) in IBD. An online literature search in various databases was conducted. After applying the inclusion and exclusion criteria, 28 reports from the 1685 results were employed for the review. The most significant SNPs potentially useful as predictive biomarkers of treatment response are linked to immunity, cytokine production, and immunorecognition.

Infección por Leishmania en pacientes con enfermedad inflamatoria intestinal: Serie de casos y revisión de la literatura / Leishmania infection in patients with inflammatory bowel disease: Case series and literature review

La infección por Leishmania spp. en pacientes diagnosticados de enfermedad inflamatoria intestinal (EII) es rara. Considerada endémica en la cuenca del Mediterráneo, sus manifestaciones son casi exclusivas de pacientes con alteración de la inmunidad celular. La mayoría de la evidencia la encontramos a través de reportes de casos en la literatura; sin que existan guías para su manejo en pacientes con EII. Presentamos tres casos de infección por Leishmania en pacientes con EII que nos llevan a realizar una revisión de la literatura actual. La terapia inmunosupresora parece favorecer esta infección, presentándose de forma atípica, con diagnóstico desafiante. El tratamiento sistémico de entrada junto a la retirada del inmunosupresor parece ser la mejor estrategia terapéutica. Se precisan estudios en zona endémica que determinen su incidencia en pacientes con EII, así como su posible asociación con la terapia inmunosupresora. Se podría sugerir la necesidad de cribado serológico previa introducción de inmunosupresores (AU)

Infection by Leishmania spp. in patients diagnosed with inflammatory bowel disease (IBD) is rare. Considered endemic in the Mediterranean basin, its manifestations are almost exclusive of patients with impaired cellular immunity. Most of the evidence is found through case reports; without guidelines for its management in patients with IBD. In this study we present three cases of Leishmania infection in patients with IBD that lead us to carry out a review of the current literature. Immunosuppressive treatment contributes to this infection, which presents atypically, with a challenging diagnosis. Initial systemic treatment with withdrawal of the immunosuppressant drug seems to be the best therapeutic strategy. Studies are needed in endemic areas to determine its incidence in IBD patients, as well as its possible association with immunosuppressive therapy. The need for serological screening prior introduction of immunosuppressive drugs could be suggested (AU)

Catalase inhibition can modulate the ability of peripheral blood T cells to undergo apoptosis in Crohn's disease.

Crohn's disease (CD) is a chronic relapsing inflammatory disorder in which defective apoptosis of mucosal T cells is postulated to produce sustained inflammation and reactive oxygen species accumulation. Whether CD T cells are intrinsically resistant to apoptosis or whether this resistance is acquired at the intestinal site needs to be clarified, as the cellular mechanisms modulate the impaired apoptosis in these cells. Here, we analysed peripheral blood T cells from patients naïve to specific CD treatment at the onset and from healthy controls. Non-activated freshly purified lymphocytes were cultured and submitted to in vitro protocols for activation (CD3/CD28 antibodies) and apoptosis (Fas antibody). Cells were analysed by flow cytometry. Caspases (3, 8, and 9) and catalase activity were measured; protein levels of bax, Bcl-2, and NF-kB were detected by western blotting, and cytokines by Luminex-based assays. The results showed that CD4 T cells from CD patients are less prone to apoptosis before they can migrate to the intestinal mucosa. Caspase-9, FasR, sIL-2Rα, IL-17A, IFNγ, IL-6, TNF-α, and IL-10 were shown to be significantly different in CD but not for the rest of the analysed biological elements. Catalase activity was significantly reduced in CD T cells, which was confirmed in ex vivo experiments in which catalase inhibition in T cells from healthy controls triggered apoptosis inhibition in a dose-dependent manner. In conclusion, apoptosis inhibition of CD T cells is a feature of these cells before they can migrate to the intestinal mucosa. Noteworthy, the impaired apoptosis of T cells can be directly influenced by catalase inhibition.

Leishmania infection in patients with inflammatory bowel disease: Case series and literature review. / Infección por Leishmania en pacientes con enfermedad inflamatoria intestinal: Serie de casos y revisión de la literatura.

Infection by Leishmania spp. in patients diagnosed with inflammatory bowel disease (IBD) is rare. Considered endemic in the Mediterranean basin, its manifestations are almost exclusive of patients with impaired cellular immunity. Most of the evidence is found through case reports; without guidelines for its management in patients with IBD. In this study we present three cases of Leishmania infection in patients with IBD that lead us to carry out a review of the current literature. Immunosuppressive treatment contributes to this infection, which presents atypically, with a challenging diagnosis. Initial systemic treatment with withdrawal of the immunosuppressant drug seems to be the best therapeutic strategy. Studies are needed in endemic areas to determine its incidence in IBD patients, as well as its possible association with immunosuppressive therapy. The need for serological screening prior introduction of immunosuppressive drugs could be suggested.

MicroRNA and granulocyte-monocyte adsorption apheresis combotherapy after inadequate response to anti-TNF agents in ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract, affecting millions of individuals throughout the world, and producing an impaired health-related quality of life. Granulocyte and monocyte apheresis (GMA) is a therapeutic option for UC management to induce remission by selective removal of activated leukocytes from bloodstream. Despite the knowledge of the important role of epigenetics in UC pathogenesis, and in the response to different treatments, nothing is known about the role of microRNAs in GMA therapy in UC patients. METHODS: Seven consecutively UC patients who started GMA in combo therapy with infliximab were recruited. Peripheral blood samples were taken before the apheresis session, at the start of the induction (S0) and at the end (S10). They were follow-up during the induction phase (10 sessions: 2 sessions for a week during 3 wk and 1 session for a week during 4 wk) of the treatment at a tertiary hospital (Hospital la Fe) and 6 mo after finishing the GMA induction therapy. MiRNA was extracted and analyzed by RT-PCR. R software and GraphPad were used. RESULTS: Clinical disease activity significantly decreased after induction therapy with GMA (median partial Mayo score 2 (IQR, 1-6) (P < .05). Fecal calprotectin value and CRP value significantly decreased after induction therapy. Five microRNAs modified their expression during GMA (unsupervised analysis): miR-342-3p, miR-215-5p, miR-376c-3p, miR-139-5p, and miR-150-5p. When a sub-analysis was performed in those patients who showed good response to apheresis treatment (n = 5), two microRNAs showed to be implicated: miR-215-5p and miR-365a-3p. These are preliminary but promising and novel results, as it is the first time, to our knowledge that microRNA profiles have been studied in the context of GMA treatment for IBD.

Real-world long-term effectiveness of ustekinumab in ulcerative colitis: results from a spanish open-label cohort.

OBJECTIVE: Ustekinumab was recently approved for the treatment of moderate-to-severe ulcerative colitis (UC). Although data from the UNIFI clinical trial are encouraging, real-world data assessing effectiveness and safety are scarce. The aim of this study was to assess the effectiveness, safety and pharmacokinetics of ustekinumab in a large cohort of refractory UC patients. METHODS: Multicenter observational study of UC patients who received ustekinumab for active disease. The Partial Mayo Score (PMS), endoscopic activity, C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at different time points. Demographic and clinical data, adverse events (AEs) and surgeries were documented. RESULTS: A total of 108 patients were analyzed from 4 referral Spanish hospitals. The clinical remission rates were 59%, 56.5%, 57% and 69% of patients at weeks 8, 16, 24 and 52, respectively. Normalization of FC was achieved in 39.6%, 41% and 51% at weeks 8, 24 and 52, respectively. CRP normalization was observed in 79%, 75% and 76.5% of patients at weeks 8, 24 and 52, respectively. Fewer previous anti-TNF agents and loss of response to anti-TNF were associated with clinical response and normalization of FC, respectively. AEs were observed in 5 patients, and 9 underwent colectomy. Ustekinumab persistence rates were 91%, 83% and 81% at 24, 48 and 96 weeks, respectively. CONCLUSIONS: Ustekinumab demonstrated, in the real-world setting, long-term effectiveness and a favorable safety profile in a cohort of refractory UC patients.

Evaluation of tolerance to mercaptopurine in patients with inflammatory bowel disease and gastrointestinal intolerance to azathioprine.

BACKGROUND: Thiopurines such as azathioprine (AZA) and mercaptopurine (MP) are commonly utilized to treat inflammatory bowel disease (IBD). Their use is frequently restricted due to gastrointestinal intolerance (GI). Previous retrospective studies have reported that AZA-intolerant patients may benefit from a switch to MP; yet the effectiveness of this strategy has not been prospectively evaluated. AIMS: To assess GI tolerance to MP in patients who are intolerant to AZA, and to identify clinical predictors of GI intolerance to AZA or MP. METHODS: A prospective, observational, single-cohort study was performed in 92 thiopurine-naïve IBD patients. They were started on a 50mg dose of AZA and escalated to 2.5mg/kg per day by week 2. Those with GI intolerance were rechallenged with a 50% dose of AZA, after which another dose escalation attempt was made. If symptoms persisted, they were switched to MP. RESULTS: Thirty (32.6%) of the recruited patients suffered from GI intolerance to AZA. Of these, 15 did not present recurrence of symptoms after rechallenge with lower doses. Of 15 intolerant patients, 14 were switched to MP. Within the MP cohort, 8 patients (57%) were also intolerant to MP, 5 (36%) had no symptoms, and 1 (7%) was lost to follow-up. Female gender was the only independent predictor of GI intolerance to AZA. CONCLUSIONS: Up to half of the AZA-intolerant patients tolerated a 50% dose rechallenge that was successfully escalated. A switch to MP was tolerated in over a third of cases whom rechallenge failed. Our strategy (challenge-rechallenge-switch) achieved an overall GI tolerance to thiopurines in most of the patients.

Personalized therapy in inflammatory bowel disease. / Terapia personalizada en la enfermedad inflamatoria intestinal.

Inflammatory bowel diseases (IBD), with ulcerative colitis and Crohn's disease being their most common presentations, comprise a spectrum of diverse disease phenotypes, exhibiting variable behaviors ranging from an indolent course to aggressive phenotypes that impact quality of life of these patients. The last two decades have been marked by the development of new medications (biological therapy and novel small molecules) with diverse mechanisms of action, which have revolutionized the management of IBD, thereby enhancing the quality of life for these patients. This landscape of multiple therapeutic options underscores the need to define which medication will benefit each patient the most and at what speed it should be started. The objective of this review is to present personalized approaches for patients with IBD, thus contributing to therapeutic management.

Encuesta Sociedad Española de Médicos de Atención Primaria (SEMERGEN) y Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre el manejo de pacientes con enfermedad inflamatoria intestinal / Spanish Society of Primary Care Physicians (SEMERGEN) and Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) survey on the management of patients with inflammatory bowel disease

Introducción: La colaboración entre Atención Primaria (AP) y Gastroenterología en la enfermedad inflamatoria intestinal (EII) es crucial para ofrecer una atención médica de alta calidad. El objetivo del presente estudio es analizar, en el ámbito nacional, la relación entre AP y los gastroenterólogos con el objetivo de conocer los aspectos de mejora en el manejo de pacientes con EII y cómo poder implementarlos, para así desarrollar posteriormente propuestas y proyectos concretos entre SEMERGEN y GETECCU. Metodología: Estudio descriptivo, observacional y transversal, realizado mediante cuestionario online anónimo entre octubre de 2021 y marzo de 2022. Resultados: Se recopilaron un total de 157 encuestas de Gastroenterología y 222 de AP. El 43,8% y el 34,3% de los gastroenterólogos y médicos de familia, respectivamente, consideraron tener una buena relación. El grado de conocimiento de los médicos de familia sobre diferentes aspectos de la EII (puntuado sobre 10) fue: aspectos clínicos 6,67±1,48, diagnósticos 6,47±1,46, terapéuticos 5,63±1,51, de seguimiento 5,53±1,68 y complicaciones 6,05±1,54. La percepción del apoyo y soporte entre ambas unidades no superó el 4,5 en una escala de 0 a 10 en ninguna de las encuestas. Las propuestas de mejora más votadas fueron: mayor coordinación entre especialistas, implantación de unidades de EII y colaboración de enfermería. Conclusión: Existen deficiencias en la relación entre AP y Gastroenterología con especial dedicación a la EII que requiere de los esfuerzos de las sociedades científicas que los representan para una mayor coordinación, con elaboración de protocolos conjuntos y medios de comunicación ágiles, rápidos y efectivos. (AU)

Introduction: Collaboration between Primary Care (PC) and Gastroenterology in inflammatory bowel disease (IBD) is crucial to provide high-quality healthcare. The aim of this study is to analyse the relationship between PC and gastroenterologists at a national level in order to identify areas for improvement in the management of patients with inflammatory bowel disease (IBD) and how to address them, with the aim of subsequently developing concrete proposals and projects between SEMERGEN and GETECCU. Methods: Descriptive, observational, cross-sectional study, was carried out using an anonymous online questionnaire between October 2021 and March 2022. Results: A total of 157 surveys from Gastroenterology and 222 from PC were collected. 43.8% and 34.3% of gastroenterologists and family practitioners, respectively, considered that there was a good relationship between the units. The level of knowledge from family practitioners regarding different aspects of IBD out of 10 was: clinical 6.67±1.48, diagnosis 6.47±1.46, treatment 5.63±1.51, follow-up 5.53±1.68 and complications 6.05±1.54. The perception of support between both units did not exceed 4.5 on a scale from 0 to 10 in either of the surveys. The most highly voted improvement proposals were better coordination between the units, implementation of IBD units, and nursing collaboration. Conclusion: There are deficiencies in the relationship between PC and Gastroenterology with special dedication to IBD that require the efforts of the scientific societies that represent them for greater coordination with the development of joint protocols and agile, fast, and effective communication channels. (AU)

The Risk of Developing Disabling Crohn's Disease: Validation of a Clinical Prediction Rule to Improve Treatment Decision Making.

BACKGROUND: Crohn's disease (CD) is characterized by the development of complications over the course of the disease. It is crucial to identify predictive factors of disabling disease, in order to target patients for early intervention. We evaluated risk factors of disabling CD and developed a prognostic model. METHODS: In total, 511 CD patients were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to identify demographic, clinical, and biological risk factors. A predictive nomogram model was developed in a subgroup of patients with noncomplicated CD (inflammatory pattern and no perianal disease). RESULTS: The rate of disabling CD within 5 years after diagnosis was 74.6%. Disabling disease was associated with gender, location of disease, requirement of steroids for the first flare, and perianal lesions. In the subgroup of patients (310) with noncomplicated CD, the rate of disabling CD was 80%. In the multivariate analysis age at onset <40 years (OR = 3.46, 95% confidence interval [CI] = 1.52-7.90), extensive disease (L3/L4) (OR = 2.67, 95% CI = 1.18-6.06), smoking habit (OR = 2.09, 95% CI = 1.03-4.27), requirement of steroids at the first flare (OR = 2.20, 95% CI = 1.09-4.45), and albumin (OR = 0.59, 95% CI = 0.36-0.96) were associated with development of disabling disease. The developed predictive nomogram based on these factors presented good discrimination, with an area under the receiver operating characteristic curve of 0.723 (95% CI: 0.670-0.830). CONCLUSION: We identified predictive factors of disabling CD and developed an easy-to-use prognostic model that may be used in clinical practice to help identify patients at high risk and address treatment effectively.

Predictive model of persistent choledocholithiasis in patients with acute biliary pancreatitis / Modelo predictivo de coledocolitiasis persistente en pacientes con pancreatitis aguda biliar

Background: Choledocholithiasis causing acute biliary pancreatitis (ABP) may migrate to the duodenum or persist in the common bile duct (CBD). We developed a model for predicting persistent choledocholithiasis (PC) in patients with ABP. Methods: This retrospective cohort study included 204 patients, age ≥18 years (mean age: 73 years, 65.7% women), admitted for ABP in 2013–2018, with at least a magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasonography (EUS), and/or endoscopic retrograde cholangiopancreatography (ERCP). Epidemiological, analytical, imaging, and endoscopic variables were compared between patients with and without PC. Multivariate logistic regression analyses were performed to develop a predictive model of PC. Results: Patients underwent MRCP (n=145, 71.1), MRCP and ERCP (n=44, 21.56%), EUS and ERCP (n=1, 0.49%), or ERCP (n=14, 6.86%). PC was detected in 49 patients (24%). PC was strongly associated with CBD dilation, detected in the emergency ultrasound (p<0.001; OR=27; 95% CI: 5.8–185.5), increased blood levels of gamma glutamyl transpeptidase, detected at 72h (p=0.008; OR=3.4; 95% CI: 1.5–8.9); and biliary sludge in the gallbladder (p=0.008; OR=0.03; 95% CI: 0.001–0.3). Conclusions: The predictive model showed a validated area under the curve (AUC) of 0.858 for detecting PC in patients with ABP. A nomogram was developed based on model results. Conclusions: The predictive model was highly effective in detecting PC in patients with ABP. Therefore, this model could be useful in clinical practice.(AU)

Antecedentes: La coledocolitiasis que provoca una pancreatitis aguda biliar (PAB) puede migrar al duodeno o persistir en el conducto biliar común (CBC). Desarrollamos un modelo para predecir la coledocolitiasis persistente (CP) en pacientes con PAB. Métodos: Este estudio de cohortes retrospectivo incluyó a 204 pacientes, edad ≥ 18 años (edad media: 73 años, 65,7% mujeres), ingresados por PAB entre los años 2013 y 2018, a los que se les realizó al menos una colangiopancreatografía por resonancia magnética (CPRM), una ultrasonografía endoscópica (USE) o una colangiopancreatografía retrógrada endoscópica (CPRE). Se compararon variables epidemiológicas, analíticas, de imagen y endoscópicas entre pacientes con y sin CP. Se realizaron análisis de regresión logística multivariante para desarrollar un modelo predictivo de CP. Resultados: Los pacientes se sometieron a CPRM (n=145, 71,1%), CPRM y CPRE (n=44, 21,56%), USE y CPRE (n=1, 0,49%) o CPRE (n=14, 6,86%). Se detectó CP en 49 pacientes (24%). La CP se asoció fuertemente con la dilatación del colédoco, detectada en la ecografía de urgencias (p <0,001; OR=27; IC del 95%: 5,8-185,5), aumento de los niveles sanguíneos de gamma glutamil transpeptidasa, detectados a las 72h (p=0,008; OR=3,4, IC del 95%: 1,5-8,9), y barro biliar en la vesícula (p=0,008; OR=0,03; IC del 95%: 0,001-0,3). El modelo predictivo alcanzó un área bajo la curva validada de 0,858 para la detección de CP en pacientes con PAB. Se desarrolló un nomograma basado en los resultados del modelo. Conclusiones: El modelo predictivo fue altamente efectivo en la detección de CP en pacientes con PAB. Por lo tanto, este modelo podría ser útil en la práctica clínica.(AU)

Immunoepigenetic Regulation of Inflammatory Bowel Disease: Current Insights into Novel Epigenetic Modulations of the Systemic Immune Response.

The immune system and environmental factors are involved in various diseases, such as inflammatory bowel disease (IBD), through their effect on genetics, which modulates immune cells. IBD encompasses two main phenotypes, Crohn's disease, and ulcerative colitis, which are manifested as chronic and systemic relapse-remitting gastrointestinal tract disorders with rising global incidence and prevalence. The pathophysiology of IBD is complex and not fully understood. Epigenetic research has resulted in valuable information for unraveling the etiology of this immune-mediated disease. Thus, the main objective of the present review is to summarize the current findings on the role of epigenetic mechanisms in IBD to shed light on their potential clinical relevance. This review focuses on the latest evidence regarding peripheral blood mononuclear cells and epigenetic changes in histone modification, DNA methylation, and telomere shortening in IBD. The various identified epigenetic DNA profiles with clinical value in IBD could be used as biomarkers for more accurately predicting disease development, treatment response, and therapy-related adverse events. Ultimately, the information presented here could be of potential relevance for future clinical practice in developing more efficient and precise medicine to improve the quality of life for patients with IBD.

Predictive model of persistent choledocholithiasis in patients with acute biliary pancreatitis.

BACKGROUND: Choledocholithiasis causing acute biliary pancreatitis (ABP) may migrate to the duodenum or persist in the common bile duct (CBD). We developed a model for predicting persistent choledocholithiasis (PC) in patients with ABP. METHODS: This retrospective cohort study included 204 patients, age ≥18 years (mean age: 73 years, 65.7% women), admitted for ABP in 2013-2018, with at least a magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasonography (EUS), and/or endoscopic retrograde cholangiopancreatography (ERCP). Epidemiological, analytical, imaging, and endoscopic variables were compared between patients with and without PC. Multivariate logistic regression analyses were performed to develop a predictive model of PC. RESULTS: Patients underwent MRCP (n=145, 71.1), MRCP and ERCP (n=44, 21.56%), EUS and ERCP (n=1, 0.49%), or ERCP (n=14, 6.86%). PC was detected in 49 patients (24%). PC was strongly associated with CBD dilation, detected in the emergency ultrasound (p<0.001; OR=27; 95% CI: 5.8-185.5), increased blood levels of gamma glutamyl transpeptidase, detected at 72h (p=0.008; OR=3.4; 95% CI: 1.5-8.9); and biliary sludge in the gallbladder (p=0.008; OR=0.03; 95% CI: 0.001-0.3). CONCLUSIONS: The predictive model showed a validated area under the curve (AUC) of 0.858 for detecting PC in patients with ABP. A nomogram was developed based on model results. CONCLUSIONS: The predictive model was highly effective in detecting PC in patients with ABP. Therefore, this model could be useful in clinical practice.

Ustekinumab and vedolizumab for the prevention of postoperative recurrence of Crohn's disease: Results from the ENEIDA registry.

BACKGROUND: Anti-TNF agents are the only effective biological agents for the prevention of postoperative recurrence (POR) in Crohn's disease (CD). However, they are contraindicated or have been shown to fail in some patients. Although ustekinumab and vedolizumab were licensed for CD some years ago, data in this setting are scarce. METHODS: All CD patients in whom ustekinumab or vedolizumab was prescribed for the prevention of POR within three months of ileocolonic resection with anastomosis were identified from the ENEIDA registry. The development of endoscopic, clinical and surgical POR was registered. RESULTS: Forty patients were treated for the prevention of POR with ustekinumab and 25 were treated with vedolizumab. Eighty per cent had at least one risk factor for POR (prior resections, active smoking, perianal disease or penetrating disease behaviour). All the patients had been exposed to anti-TNF therapy. After a median follow-up of 17 and 26 months, the cumulative probability of clinical POR at 12 months after surgery was 32% and 30% for ustekinumab and vedolizumab, respectively. Endoscopic assessment within the first 18 months after surgery was available for 80% of the patients on ustekinumab and 70% for those on vedolizumab. The rate of endoscopic POR was 42% for ustekinumab and 40% for vedolizumab. One patient treated with ustekinumab and two with vedolizumab underwent a new intestinal resection. CONCLUSIONS: Ustekinumab and vedolizumab seem to be effective in the prevention of POR in patients at high risk. Our results warrant controlled trials comparing these drugs with conventional therapies.

Should Inflammatory Bowel Disease Clinicians Provide Their Patients with e-Health Resources? Patients' and Professionals' Perspectives.

Introduction: The internet is emerging as a source of information for patients with inflammatory bowel disease (IBD). However, it is not always reliable and may cause anxiety. We aim to assess patients' information habits and patients' and professionals' perceptions of a national website integrated as an educational resource for the IBD unit. Methods: Patients aged 18-65 years, comfortable with the internet, and attending follow-ups at participating IBD units (March-June 2019) and their professionals were invited to evaluate a recommended website through an online survey. Results: Three hundred eighty-nine patients and 95 professionals completed the survey. The internet (n = 109; 27.4%) was the second preferred source of information after the health care team (n = 229; 57.5%). Eighty percent of patients searched the internet for information on their disease and 28.6% did so at least once a week (n = 114), especially newly diagnosed ones (<2 years). Patients valued a website recommended by their professional (n = 379; 95.2%) and endorsed by the National Working Group (n = 377; 94.7%). They would attend online educational initiatives on the website (n = 279; 70.1%) and complete periodical surveys to improve its usefulness (n = 338; 84.9%). According to IBD professionals, this type of website is the best patient source of supplementary information (n = 76; 80%) and they "prescribe" it to most patients (67.0 ± 25.2%), especially the newly diagnosed patients (52.7 ± 26.5%). It effectively integrates routine face-to-face education (n = 95; 100%). Conclusions: Patients of IBD units, especially newly diagnosed ones, appreciate a trusted e-Health resource to back up professional information. The favorable opinion of patients and professionals will allow its use in training interventions.

Spanish Society of Primary Care Physicians (SEMERGEN) and Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) survey on the management of patients with inflammatory bowel disease. / Encuesta Sociedad Española de Médicos de Atención Primaria (SEMERGEN) y Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre el manejo de pacientes con enfermedad inflamatoria intestinal.

INTRODUCTION: Collaboration between Primary Care (PC) and Gastroenterology in inflammatory bowel disease (IBD) is crucial to provide high-quality healthcare. The aim of this study is to analyse the relationship between PC and gastroenterologists at a national level in order to identify areas for improvement in the management of patients with inflammatory bowel disease (IBD) and how to address them, with the aim of subsequently developing concrete proposals and projects between SEMERGEN and GETECCU. METHODS: Descriptive, observational, cross-sectional study, was carried out using an anonymous online questionnaire between October 2021 and March 2022. RESULTS: A total of 157 surveys from Gastroenterology and 222 from PC were collected. 43.8% and 34.3% of gastroenterologists and family practitioners, respectively, considered that there was a good relationship between the units. The level of knowledge from family practitioners regarding different aspects of IBD out of 10 was: clinical 6.67±1.48, diagnosis 6.47±1.46, treatment 5.63±1.51, follow-up 5.53±1.68 and complications 6.05±1.54. The perception of support between both units did not exceed 4.5 on a scale from 0 to 10 in either of the surveys. The most highly voted improvement proposals were better coordination between the units, implementation of IBD units, and nursing collaboration. CONCLUSION: There are deficiencies in the relationship between PC and Gastroenterology with special dedication to IBD that require the efforts of the scientific societies that represent them for greater coordination with the development of joint protocols and agile, fast, and effective communication channels.

The Genetic Diversity and Dysfunctionality of Catalase Associated with a Worse Outcome in Crohn's Disease.

Chronic gut inflammation in Crohn's disease (CD) is associated with an increase in oxidative stress and an imbalance of antioxidant enzymes. We have previously shown that catalase (CAT) activity is permanently inhibited by CD. The purpose of the study was to determine whether there is any relationship between the single nucleotide polymorphisms (SNPs) in the CAT enzyme and the potential risk of CD associated with high levels of oxidative stress. Additionally, we used protein and regulation analyses to determine what causes long-term CAT inhibition in peripheral white mononuclear cells (PWMCs) in both active and inactive CD. We first used a retrospective cohort of 598 patients with CD and 625 age-matched healthy controls (ENEIDA registry) for the genotype analysis. A second human cohort was used to study the functional and regulatory mechanisms of CAT in CD. We isolated PWMCs from CD patients at the onset of the disease (naïve CD patients). In the genotype-association SNP analysis, the CAT SNPs rs1001179, rs475043, and rs525938 showed a significant association with CD (p < 0.001). Smoking CD patients with the CAT SNP rs475043 A/G genotype had significantly more often penetrating disease (p = 0.009). The gene expression and protein levels of CAT were permanently reduced in the active and inactive CD patients. The inhibition of CAT activity in the PWMCs of the CD patients was related to a low concentration of CAT protein caused by the downregulation of CAT-gene transcription. Our study suggests an association between CAT SNPs and the risk of CD that may explain permanent CAT inhibition in CD patients together with low CAT gene and protein expression.

Psychosocial impact of the COVID-19 pandemic on patients with inflammatory bowel disease in Spain. A post lockdown reflection / Impacto psicosocial de la pandemia de COVID-19 en pacientes con enfermedad inflamatoria intestinal en España. Una reflexión posterior al confinamiento

Objectives: This multicenter cross-sectional study was conducted to assess the psychosocial impact of COVID-19 on patients with inflammatory bowel disease (IBD) in Spain during lockdown and the first wave of the pandemic. Patients and methods: A self-report questionnaire that integrated the Spanish version of the Depression, Anxiety and Stress Scale-21 items (DASS-21) and the Perceived Stress Questionnaire (PSS) was designed to gather sociodemographic data and information related to the effects of lockdown on the lives of IBD patients. Twelve IBD units invited their patients to answer the anonymous online survey between the 1st July and the 25th August 2020. Results: Of the 693 survey participants with IBD, 67% were women and the mean age was 43 (SD 12). Sixty-one percent had ulcerative colitis, 36% Crohn's disease and 3% indeterminate colitis. DASS-21 scores indicate that during lockdown the estimated prevalence of depression was 11% [95% CI 8.2–13%], anxiety 20% [95% CI 17 to 23%] and stress 18% [95% CI 8.2–13%]. Multivariate analysis showed that the perceived high risk of COVID-19 infection because of having IBD and maladaptation to government measures to reduce the spread of disease doubled the risk of anxiety and stress during lockdown. Conclusions: In the short-term, lockdown during the COVID-19 pandemic seemed to have an impact on the already affected mental health of our IBD patients in Spain.(AU)

Objetivos: Este estudio transversal multicéntrico se llevó a cabo para evaluar el impacto psicosocial de la COVID-19 en pacientes con enfermedad inflamatoria intestinal (EII) en España durante el confinamiento y la primera ola de la pandemia. Pacientes y métodos: Se diseñó un cuestionario de autoinforme que integraba la versión española de la Escala de Depresión, Ansiedad y Estrés-21 ítems (DASS-21) y el Cuestionario de Estrés Percibido (PSS) para recoger datos sociodemográficos e información relacionada con los efectos del confinamiento en la vida de los pacientes con EII. Doce unidades de EII invitaron a sus pacientes a responder a la encuesta anónima en línea entre el 1 de julio y el 25 de agosto de 2020. Resultados: De los 693 participantes en la encuesta con EII, el 67% eran mujeres y la edad media era de 43 años (DE 12). El 61% tenía colitis ulcerosa, el 36% enfermedad de Crohn y el 3% colitis indeterminada. Las puntuaciones del DASS-21 indican que durante el encierro la prevalencia estimada de depresión fue del 11% [IC 95%: 8,2-13%], de ansiedad del 20% [IC 95%: 17-23%] y de estrés del 18% [IC 95%: 8,2-13%]. El análisis multivariante mostró que la percepción de alto riesgo de infección por COVID-19 por tener EII y la inadaptación a las medidas gubernamentales para reducir la propagación de la enfermedad duplicaban el riesgo de ansiedad y estrés durante el encierro. Conclusiones: A corto plazo, el confinamiento durante la pandemia de COVID-19 pareció tener un impacto en la ya afectada salud mental de nuestros pacientes con EII en España.(AU)

Changes in the management of IBD patients since the onset of COVID-19 pandemic. A path toward the implementation of telemedicine in Spain? / Cambios en el manejo de la EII desde la pandemia por COVID-19. ¿Un nuevo inicio de la telemedicina en España?

Background: COVID-19 pandemic increased medical services demand aside from interrupting daily clinical practice for other diseases such as inflammatory bowel disease (IBD). Here we present the results of a survey to gain the perception of IBD specialists in their patient-management using telemedicine in their daily practice. Methods: This was an observational survey study among physicians focused on IBD (gastroenterologist, surgeons, and pediatricians) members of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU), the Spanish Association of Gastroenterology (AEG), and the Spanish Association of Coloproctology (AECP), regarding changes of management of IBD patients. Results: We received a total of 269 responses to the survey (from May to June 2020). Before the pandemic, nearly all the respondents reported performing very frequently their visits face-to-face (n=251, 93.3%) while, during the pandemic, the telephone visits were the most frequent visits performed (n=138, 51.3%). Regarding communication difficulties, 157 (58.4%) respondents reported the impossibility of performing a proper examination as the most relevant issue. Also, 114 (42.4%) respondents considered remote visits more time-consuming than face-to-face visits. Most gastroenterologists (n=188, 83.2%) considered patients with active perianal disease in special need of face-to-face consultation and more than half of the surgeons (n=35, 50.7%) reported having performed an immediate postoperative follow-up remotely. Conclusions: Most IBD units have implemented remote visits during the pandemic, but most professionals found them more time-consuming and unsuitable for some disease profiles. Therefore, there is a need for the development of better telemedicine systems that can meet professionals’ and patients’ requirements.(AU)

Introducción: La pandemia por COVID-19ha supuesto un incremento en la demanda de atención sanitaria y ha modificado el modelo asistencial de algunas patologías como la enfermedad inflamatoria intestinal (EII). Presentamos los resultados de una encuesta sobre el papel de la telemedicina en el manejo de pacientes con EII. Material y métodos: Estudio observacional mediante encuesta dirigida a gastroenterólogos, cirujanos y pediatras especializados en EII, miembros del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa, la Asociación Española de Gastroenterología y/o la Asociación Española de Coloproctología. Resultados: Recibimos un total de 269 respuestas (mayo a junio de 2020). Antes de la pandemia, el 93,3% de los participantes afirmó llevar a cabo la mayor parte de sus consultas de manera presencial. Durante la pandemia, la consulta telefónica se ha convertido en la modalidad preferida por el 51,3%. El principal inconveniente de la asistencia telemática fue la imposibilidad de llevar a cabo una exploración física según el 58,4%. Además, el 42,4% aseguró emplear más tiempo en este tipo de consultas. Entre gastroenterólogos, el 83,2% consideró que el paciente que más puede beneficiarse de la visita presencial es aquel con enfermedad perianal activa. Y, por último, el 50,7% de los cirujanos afirmó haber realizado controles remotos en el postoperatorio inmediato. Conclusiones: Si bien las unidades de EII han implementado durante la pandemia herramientas de telemedicina, muchos de los encuestados encontraron dificultades en su implementación. Es necesario adecuar y mejorar estos nuevos canales de asistencia remota para satisfacer las necesidades de profesionales y pacientes.(AU)

The characteristics of the stricture, but not the ongoing treatment, could influence the outcome of endoscopic dilation in recurrent Crohn's disease / Las características de la estenosis, pero no el tratamiento, podrían influir en el resultado de la dilatación endoscópica en la enfermedad de Crohn recurrente

Aim: Stricture is one of the main complications of Crohn's disease (CD). Among the main conservative therapeutic alternatives, endoscopic balloon dilation (EBD) of the strictures stands out, which can improve the symptoms and delay or even avoid the need for more surgeries. The main aim of this study was to evaluate the efficacy of the EBD in CD patients with post-surgical anastomotic strictures from a previous surgery. Patients and methods: An observational study of a cohort of 32 patients with CD who underwent EBD due to uncomplicated strictures at a tertiary hospital, since 2009. Demographic, clinical and disease variables, medical treatments and previous surgeries and types, analytical variables at the time of dilation, number of dilations, complications and need for subsequent surgery were collected by searching data in clinical records. Results: Thirty-two patients were included, performing a total of 63 endoscopic dilations. A technical success of 63.5%, a therapeutic success by dilation of 58.75% and a therapeutic success per patient of 62.5% were achieved. Regarding complications, the percentage of post-dilation adverse events was 3.2% and post-dilation incidents were 4.8%. Thirty EBD did not need any medical treatment modification, 9 EBD remained untreated and 12 EBD required further surgery. The length of the strictures, but not the ongoing treatment, was the only statistically significant factor of therapeutic success by dilation and per patient. Conclusions: EBD seems a safe technique in short post-surgical strictures, can avoid the need for new surgery and prevents unnecessary immunosuppression in patients with CD anastomotic strictures.(AU)

Objetivo: La estenosis es una de las principales complicaciones de la enfermedad de Crohn (EC). La dilatación endoscópica con balón (DEB) es una de las principales alternativas terapéuticas para mejorar los síntomas y retrasar o evitar nuevas cirugías. El objetivo principal fue evaluar la eficacia de la DEB en pacientes con EC y estenosis anastomótica posquirúrgica. Pacientes y métodos: Estudio observacional de una cohorte de 32 pacientes con EC tratados con DEB por estenosis no complicadas en un hospital terciario, desde 2009. Se recogieron variables demográficas, clínicas y de la enfermedad, tratamientos médicos y cirugías previas, variables analíticas en el momento de la dilatación, número de dilataciones, complicaciones y necesidad de cirugía posterior mediante la búsqueda de datos en las historias clínicas. Resultados: Se incluyó a 32 pacientes, con un total de 63 dilataciones endoscópicas. Se obtuvo un éxito técnico del 63,5%, un éxito terapéutico por dilatación del 58,75% y un éxito terapéutico por paciente del 62,5%. En cuanto a las complicaciones, el porcentaje de eventos adversos fue del 3,17% y de incidentes del 4,8%. No necesitaron ninguna modificación del tratamiento médico 30 DEB, 9 permanecieron sin tratamiento y 12 requirieron una nueva cirugía. La longitud de la estenosis, pero no el tratamiento en curso, fue el único factor estadísticamente significativo del éxito terapéutico por dilatación y por paciente. Conclusiones: La DEB parece una técnica segura en las estenosis posquirúrgicas cortas, ya que podría evitar nuevas cirugías y evitar la inmunosupresión innecesaria en pacientes con estenosis anastomóticas de EC.(AU)