Microbiota Sensing by Mincle-Syk Axis in Dendritic Cells Regulates Interleukin-17 and -22 Production and Promotes Intestinal Barrier Integrity.

Production of interleukin-17 (IL-17) and IL-22 by T helper 17 (Th17) cells and group 3 innate lymphoid cells (ILC3s) in response to the gut microbiota ensures maintenance of intestinal barrier function. Here, we examined the mechanisms whereby the immune system detects microbiota in the steady state. A Syk-kinase-coupled signaling pathway in dendritic cells (DCs) was critical for commensal-dependent production of IL-17 and IL-22 by CD4+ T cells. The Syk-coupled C-type lectin receptor Mincle detected mucosal-resident commensals in the Peyer's patches (PPs), triggered IL-6 and IL-23p19 expression, and thereby regulated function of intestinal Th17- and IL-17-secreting ILCs. Mice deficient in Mincle or with selective depletion of Syk in CD11c+ cells had impaired production of intestinal RegIIIγ and IgA and increased systemic translocation of gut microbiota. Consequently, Mincle deficiency led to liver inflammation and deregulated lipid metabolism. Thus, sensing of commensals by Mincle and Syk signaling in CD11c+ cells reinforces intestinal immune barrier and promotes host-microbiota mutualism, preventing systemic inflammation.

Rates of Adverse Events in Patients With Ulcerative Colitis Undergoing Colectomy During Treatment With Tofacitinib vs Biologics: A Multicenter Observational Study.

INTRODUCTION: Patients with ulcerative colitis (UC) receiving immunosuppressive drugs are at substantial risk of colectomy. We aimed to assess the risk of postoperative complications of tofacitinib exposure before colectomy in comparison with biologics. METHODS: A multicenter, retrospective, observational study was conducted in patients with UC who underwent total colectomy for medically refractory disease, exposed to tofacitinib or a biologic before surgery. Primary outcome was the occurrence of any complication within 30 (early) and 90 (late) days after surgery. Secondary outcomes were the occurrence of infections, sepsis, surgical site complications, venous thromboembolic events (VTE), hospital readmissions, and redo surgery within the same timepoints. RESULTS: Three hundred one patients (64 tofacitinib, 162 anti-tumor necrosis factor-α agents, 54 vedolizumab, and 21 ustekinumab) were included. No significant differences were reported in any outcome, except for a higher rate of early VTE with anti-tumor necrosis factor-α agents ( P = 0.047) and of late VTE with vedolizumab ( P = 0.03). In the multivariate analysis, drug class was not associated with a higher risk of any early and late complications. Urgent colectomy increased the risk of any early (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.06-3.48) complications, early hospital readmission (OR 4.79, 95% CI 1.12-20.58), and early redo surgery (OR 7.49, 95% CI 1.17-47.85). A high steroid dose increased the risk of any early complications (OR 1.96, 95% CI 1.08-3.57), early surgical site complications (OR 2.03, 95% CI 1.01-4.09), and early redo surgery (OR 7.52, 95% CI 1.42-39.82). Laparoscopic surgery decreased the risk of any early complications (OR 0.54, 95% CI 0.29-1.00), early infections (OR 0.39, 95% CI 0.18-0.85), and late hospital readmissions (OR 0.34, 95% CI 0.12-1.00). DISCUSSION: Preoperative tofacitinib treatment demonstrated a postoperative safety profile comparable with biologics in patients with UC undergoing colectomy.

An international multicentre study of SwiTching from Intravenous to subcutaneous inflixiMab and vEdolizumab in inflammatory bowel diseases: The TIME study.

BACKGROUND AND AIMS: Subcutaneous (SC) formulations of infliximab (IFX) and vedolizumab (VDZ) are approved for the treatment of inflammatory bowel diseases (IBDs). Our aim was to evaluate the effectiveness of switching from intravenous (IV) to SC formulations of IFX and VDZ in IBDs. METHODS: This multicentre, retrospective study collected data of adult patients with Crohn's disease (CD) or ulcerative colitis (UC) switched to SC IFX or VDZ. The primary endpoint was clinical remission at 12 months stratified based on timing of switch. A composite endpoint consisting of therapy discontinuation, reverse-switch, need for steroids, and drug optimization was evaluated. A multivariate analysis investigated the association between patients' characteristics and outcomes. RESULTS: Two hundred and thirty-one patients (59% UC, 53% male, mean age 44 ± 15 years, 68% IFX) from 13 centres were included. The switch occurred at Week 6 in a third of cases (36%). Median time to switch was 13 months. Most patients switched to SC IFX and VDZ were in clinical remission at 3 (87% and 77%), 6 (86% and 83%) and 12 (63% and 60%) months. In the multivariate analysis, there was no difference in clinical remission rate at 12 months; however, patients switched at Week 6 had a higher rate of experiencing any therapeutic changes at 3 (false discovery rate (FDR) = .002), 6 (FDR <1 × 10-10) or 12 months (FDR = .08). Clinical disease activity at baseline (only in UC) (FDR = .07) and previous exposure to biologics (FDR = .001) were risk factors for composite endpoint at 6 and 12 months. CONCLUSION: SC IFX and VDZ are effective in daily clinical practice in IBD patients. Switching patients in remission reduces the risk of negative outcomes.

Genetic biomarkers of methotrexate response and safety in Crohn's disease: Data from the Spanish ENEIDA registry.

AIMS: Methotrexate (MTX) is used to induce and maintain remission in patients with steroid-dependent Crohn's disease (CD). Despite its proven efficacy, its use is limited due to associated adverse events. Polymorphisms involving folate pathway genes might influence MTX efficacy and toxicity. We aimed to assess the impact of certain polymorphisms on the therapeutic outcomes of MTX in CD. METHODS: Patients with CD who exclusively followed MTX monotherapy and fulfilled inclusion criteria were identified from the GETECCU ENEIDA registry. Variants of ATIC, DHFR, MTHFR, SLC19A1, ABCB1 and ABCC3 genes were analysed and their association with efficacy and toxicity was assessed. RESULTS: A total of 129 patients were included in the analysis. MTX was used at a median weekly dose of 25 mg (interquartile range, 15-25 mg) and a median time of 14 months (interquartile range, 4-52 months). Thirty-seven percent of the patients achieved disease remission with MTX monotherapy, while 34% were nonresponders (MTX failure). MTX-related toxicity occurred in 40 patients (30%), leading to MTX discontinuation in 19%. DHFR rs408626 (odds ratio [OR] 3.12, 95% confidence interval [CI] 1.22-7.69; P = .017) and MTHFR rs1801133 (OR 2.86, 95% CI 1.23-6.68; P = .015) variants, and smoking (OR 2.61, 95% CI 1.12-6.05; P = .026) were associated with a higher risk of MTX failure. Additionally, the MTHFR rs1801131 variant was associated with a higher risk of MTX-related adverse effects (OR 2.78, 95% CI 1.26-6.13, P = .011). CONCLUSION: Our study shows that variants of MTHFR and DHFR genes may be associated with MTX efficacy and adverse events in patients with CD.

Evaluation of Genetic Variants Associated with the Risk of Thiopurine-Related Pancreatitis: A Case Control Study from ENEIDA Registry.

INTRODUCTION: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled; a total of 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.

Telemonitoring with TECCU of active Inflammatory Bowel Disease is Not Inferior to Standard Care: Short-term Results of a Multicentre Randomized Controlled Trial of GETECCU.

BACKGROUND: Telemonitoring is not consistently superior to standard care for inflammatory bowel disease (IBD), yet non-inferiority may be an acceptable outcome if remote care is more efficient. OBJECTIVE: To compare the remission time and quality of life of patients with an active IBD controlled by standard care or through the TECCU App (Telemonitoring of Crohn´s Disease and Ulcerative Colitis). METHODS: A 2-arm, randomized, multicentre trial with a non-inferiority design was performed at 24 Spanish hospitals on adult patients with IBD who initiated immunosuppressant or biological therapy. Patients were randomized into telemonitoring (G_TECCU) or standard care groups (G_Control). The follow-up schedule was based on telemonitoring contacts through the TECCU App in G_TECCU, and on in-person visits and telephone calls in G_Control, as in clinical practice. In both groups, treatment was adjusted according to the evolution of disease activity and medication adherence, which were measured through specific indices and biological markers at each check-up. The primary outcome was time in remission after 12-weeks, with quality of life, medication adherence, adverse events and patient satisfaction as secondary outcomes. RESULTS: Of 169 patients enrolled, 158 were randomized, and 150 were analyzed per protocol: telemonitoring (n=71); control (n=79). After 12-week, the time in clinical remission was not inferior after telemonitoring (4.20 ±3.73 weeks) to that in the controls (4.32 ±3.28 weeks), with a mean difference between arms of -0.12 weeks (95% CI -1.25-,1.01), non-inferiority p=0.017). The mean reduction of CRP values was -15.40 mg/L (SD=90.15, P =0.195) in G_TECCU and -13.16 mg/L (SD=54.61, P =0.053) in G_control, without significant differences between the two arms (P=.726). Similarly, the mean improvement of FC levels was 832.3 mg/L (SD=1825.0, P=.003) in G_TECCU and 1073.5 mg/L in G_Control (SD=3105.7, P=.03), but differences were not significant (P=.965). Quality of life improved in both groups, with a mean rise in the IBDQ-9 score of 13.44 points in G_TECCU (SD=19.1; P<.001) and 18.23 points [SD=22.9]; P=.001) in G_Control. Moreover, the proportion of patients who adhered to their medication rose significantly from 35.2% (25/71) to 67.6% (48/71) in G_TECCU (P=.001) and from 45.6% (36/79) to 73.4% (58/79) in G_Control (P=.001). Satisfaction remained stable around 90%, although non-inferiority was not demonstrated for secondary outcomes. CONCLUSIONS: Telemonitoring patients with active IBD is not inferior to standard care to achieve and maintain short-term remission. TECCU may be an alternative follow-up tool if the improved health outcomes and costs are confirmed in the long-term. CLINICALTRIAL: The trial is registered at ClinicalTrials.gov with the identifier NCT06031038; https://classic.clinicaltrials.gov/ct2/show/NCT06031038. INTERNATIONAL REGISTERED REPORT: RR2-10.2196/resprot.9639.

Validation of the Spanish version of the Perceived Control Scale: Perceived Constraints on Personal Control and Perceived Mastery.

OBJECTIVES: Perceived control is a relevant variable for understanding middle and older adults' mental health. The Perceived Control Scale has two dimensions, Perceived Constraints on Personal Control and Perceived Mastery, and is a widely used instrument for assessing perceived control in adults. The aim of this study was to analyze the psychometric properties of the Spanish version of the Perceived Control Scale with data from two different studies. METHOD: In Study 1, 348 older adults between 60 and 92 years old were assessed through face-to-face assessments. In Study 2, 334 adults between 40 and 90 years completed an online survey. Perceived control, self-perceptions of aging, and anxiety and depressive symptomatology were assessed. An exploratory (Study 1) and confirmatory (Study 2) factor analysis of the Perceived Control Scale were performed, and reliability and its relationship with the other assessed variables were evaluated. RESULTS: Results from parallel, exploratory, and confirmatory factor analyses suggested that the Spanish version of the Perceived Control Scale has a bidimensional structure: Perceived Constraints on Personal Control and Perceived Mastery. Good internal consistency was found for the scale in both samples. The results revealed negative and significant associations with negative self-perceptions of aging, and anxiety and depressive symptomatology. CONCLUSION: The Spanish version of the Perceived Control Scale shows good psychometric properties which endorse its use with middle-aged and older adults assessed either face-to-face or through online surveys.

'Who tells me when to stay active or to leave?' age differences in and predictors of endorsement of prescriptive views of aging.

OBJECTIVES: Prescriptive views of aging (PVoA) are normative age-based expectations about age-appropriate behavior for older adults, e.g. that they should stay fit/active (active aging norms) but also behave altruistically toward younger generations (altruistic disengagement norms). We aimed at examining age differences in endorsement of active aging and altruistic disengagement and investigated predictors of endorsement. METHOD: In the AGEISM Germany survey, a representative sample of N = 1,915 German participants was recruited, covering a wide age range (Mage=56.57 years, 16-96 years). Cross-sectional data was collected via computer-assisted telephone interviews. RESULTS: Active aging was more strongly endorsed than altruistic disengagement. Endorsement of both PVoA was higher in older age groups - even more pronounced for altruistic disengagement. Endorsement of both norms was positively associated with positive age stereotypes. Furthermore, active aging was predicted by age centrality whereas altruistic disengagement was predicted by negative age stereotypes. Age was still a robust predictor of PVoA even after entering additional predictors. CONCLUSION: Although associated, prescriptive age norms (i.e. beliefs how older people should behave) and descriptive age norms (i.e. beliefs about how older adults and the aging process are like) represent partly independent belief systems, highlighting the importance to assess & further investigate predictors and consequences of PVoA, which become more prevalent with age.

Long Non-Coding RNAs and Their Potential Role as Biomarkers in Inflammatory Bowel Disease.

Inflammatory bowel disease is a chronic inflammatory disease that encompasses entities such as Crohn's disease and ulcerative colitis. Its incidence has risen in newly industrialised countries over time, turning it into a global disease. Lately, studies on inflammatory bowel disease have focused on finding non-invasive and specific biomarkers. Long non-coding RNAs may play a role in the pathophysiology of inflammatory bowel disease and therefore they may be considered as potential biomarkers for this disease. In the present article, we review information in the literature on the relationship between long non-coding RNAs and inflammatory bowel disease. We especially focus on understanding the potential function of these RNAs as non-invasive biomarkers, providing information that may be helpful for future studies in the field.

Tips and tricks for writing a manuscript to publish in a biomedical journal. / Consejos para escribir un manuscrito y publicarlo en una revista biomédica.

Science barely exists until it is published. It is only then that the information surpasses the limits of the author and can be shared by the scientific community. Although scientific articles must follow a rigidly defined structure, there is still room to tell a fascinating story, one that clearly conveys the science and is, at the same time, enjoyable for the reader. To do this, we must use the attributes that characterize good scientific style, with simple, clear, precise, direct, rigorous, and consistent language. Authorship implies authenticity and authority, and considering a researcher as an author entails rights and responsibilities. Scientific writing is not easy, it requires patience and practice; learning to write well is a lifelong task. With the philosophy that most of the qualities required to proficiently write a scientific article depend on attitude, and can be learned and improved upon, in this manuscript we will share with the reader a series of recommendations (based on our own experiences, both positive and negative), which we consider important for writing and successfully publishing. We will focus on the so-called «original¼ articles (as opposed to review articles, although many of the recommendations presented are applicable to both). Our main purpose is to encourage researchers to take the necessary step and face the challenge of becoming authors of their own scientific articles and successfully publishing their research.

Headache in patients with inflammatory bowel disease: Migraine prevalence according to the Migraine Screening-Questionnaire (MS-Q) and headache characteristics.

BACKGROUND: The gut-brain axis describes a complex bidirectional association between neurological and gastrointestinal (GI) disorders. In patients with migraine, GI comorbidities are common. We aimed to evaluate the presence of migraine among patients with inflammatory bowel disease (IBD) according to Migraine Screen-Questionnaire (MS-Q) and describe the headache characteristics compared to a control group. Additionally, we explored the relationship between migraine and IBD severities. METHODS: We performed a cross-sectional study through an online survey including patients from the IBD Unit at our tertiary hospital. Clinical and demographic variables were collected. MS-Q was used for migraine evaluation. Headache disability scale HIT-6, anxiety-depression scale HADS, sleep scale ISI, and activity scale Harvey-Bradshaw and Partial Mayo scores were also included. RESULTS: We evaluated 66 IBD patients and 47 controls. Among IBD patients, 28/66 (42%) were women, mean age 42 years and 23/66 (34.84%) had ulcerative colitis. MS-Q was positive in 13/49 (26.5%) of IBD patients and 4/31 (12.91%) controls (p=0.172). Among IBD patients, headache was unilateral in 5/13 (38%) and throbbing in 10/13 (77%). Migraine was associated with female sex (p=0.006), lower height (p=0.003) and weight (p=0.002), anti-TNF treatment (p=0.035). We did not find any association between HIT-6 and IBD activity scales scores. CONCLUSIONS: Migraine presence according to MS-Q could be higher in patients with IBD than controls. We recommend migraine screening in these patients, especially in female patients with lower height and weight and anti-TNF treatment.

Impact of mesalazine on the response to COVID-19 vaccination in patients with inflammatory bowel disease: Results of a prospective multicentre study of GETECCU (VACOVEII study). / Impacto de la mesalazina en la respuesta a la vacunación contra la COVID-19 en pacientes con enfermedad inflamatoria intestinal. Resultados de un estudio prospectivo multicéntrico de GETECCU (VACOVEII).

OBJECTIVE: The recommendations of the Spanish Ministry of Health on vaccination in risk groups include mesalazine among the treatments with a possible negative effect on its effectiveness. However, this is not the recommendation of most experts. Our objective was to evaluate the effect of mesalazine on the humoral response to the SARS-CoV-2 vaccine in patients with inflammatory bowel disease (IBD). METHODS: VACOVEII is a Spanish, prospective, multicenter study promoted by GETECCU, which evaluates the effectiveness of the SARS-CoV-2 vaccine in patients with IBD. This study includes IBD patients who have recieved the full vaccination schedule and without previous COVID-19 infection. Seroconversion was set at 260BAU/mL (centralized determination) and was assessed 6 months after full vaccination. In this subanalysis of the study, we compare the effectiveness of the vaccine between patients treated with mesalazine and patients without treatment. RESULTS: A total of 124 patients without immunosuppressive therapy were included, of which 32 did not receive any treatment and 92 received only mesalazine. Six months after full vaccination, no significant differences are observed in the mean concentrations of IgG anti-S between both groups. In the multivariate analysis, antibody titers were independently associated with the use of mRNA vaccines and with SARS-CoV-2 infection. CONCLUSION: Mesalazine does not have a negative effect on the response to SARS-CoV-2 vaccines in IBD patients.

Real-World Evidence of Tofacinitib in Ulcerative Colitis: Short-Term and Long-Term Effectiveness and Safety.

INTRODUCTION: The objective of this study was to assess the durability, short-term and long-term effectiveness, and safety of tofacitinib in ulcerative colitis (UC) in clinical practice. METHODS: This is a retrospective multicenter study including patients with UC who had received the first tofacitinib dose at least 8 weeks before the inclusion. Clinical effectiveness was based on partial Mayo score. RESULTS: A total of 408 patients were included. Of them, 184 (45%) withdrew tofacitinib during follow-up (mean = 18 months). The probability of maintaining tofacitinib was 67% at 6 m, 58% at 12 m, and 49% at 24 m. The main reason for tofacitinib withdrawal was primary nonresponse (44%). Older age at the start of tofacitinib and a higher severity of clinical activity were associated with tofacitinib withdrawal. The proportion of patients in remission was 38% at week 4, 45% at week 8, and 47% at week 16. Having moderate-to-severe vs mild disease activity at baseline and older age at tofacitinib start were associated with a lower and higher likelihood of remission at week 8, respectively. Of 171 patients in remission at week 8, 83 (49%) relapsed. The probability of maintaining response was 66% at 6 m and 54% at 12 m. There were 93 adverse events related to tofacitinib treatment (including 2 pulmonary thromboembolisms [in patients with risk factors] and 2 peripheral vascular thrombosis), and 29 led to tofacitinib discontinuation. DISCUSSION: Tofacitinib is effective in both short-term and long-term in patients with UC. The safety profile is similar to that previously reported.

Associations Between Dysfunctional Thoughts, Leisure Activities, and IL-6 in Caregivers of Family Members With Dementia.

OBJECTIVE: Dementia caregiving is associated with negative physical health consequences, including inflammation processes. The objective of this study was to analyze the associations between dysfunctional thoughts, frequency of leisure activities, and interleukin 6 (IL-6) in a sample of dementia family caregivers. METHODS: One hundred forty dementia caregivers participated in this cross-sectional study. The relationships among caregivers' dysfunctional thoughts, leisure activities, and IL-6 were adjusted for demographic characteristics, stressors, and physical and mental health indicators in a linear regression analysis. RESULTS: Higher levels of dysfunctional thoughts ( t = -2.02, p = .045) were significantly associated with lower frequency of leisure activities. In turn, lower frequency of leisure activities was significantly associated with higher levels of IL-6 ( t = -2.03, p = .045). Dysfunctional thoughts were no longer significantly associated with IL-6 levels when both dysfunctional thoughts and leisure activities were included in the same model ( t = 1.78, p = .076). A significant indirect effect was found for the association between higher levels of dysfunctional thoughts and higher levels of IL-6 (standardized indirect effect = 0.036, bootstrap standard error = 0.026, 95% confidence interval = 0.0001-0.1000) through its association with fewer leisure activities. CONCLUSIONS: Our findings suggest that the direct effect of caregivers' dysfunctional thoughts on IL-6 may be mediated by the impact on caregivers' frequency of leisure activities. Results suggest that training caregivers in reducing dysfunctional thoughts to thereby increase leisure activities may be useful in reducing inflammation.

'I feel old and have aging stereotypes'. Internalized aging stereotypes and older adults' mental health: the mediational role of loneliness.

OBJECTIVES: The main objective of this study was to analyze the role of aging stereotype activation (when older adults with aging stereotypes begin to consider themselves as older persons) in the relationship between ageist stereotypes, depressive, anxiety, loneliness, and comorbid anxiety-depressive symptoms. METHODS: Participants were 182 autonomous community-dwelling people between 60 and 88 (mean age = 72.30; SD = 5.53). Three path models were tested exploring the role of considering oneself as an older person as a moderator variable. Ageist stereotypes were included as the independent variable, loneliness as the mediating variable, and anxiety symptoms, depressive symptoms, and comorbid anxiety-depressive symptoms as dependent variables for each model. RESULTS: The results suggest an influence of ageist stereotypes on anxiety, depressive, and comorbid anxiety-depressive symptoms only in older adults who consider themselves as older persons, and mediated by loneliness. CONCLUSION: This study suggests that, when someone considers him or herself as an older person, ageist stereotypes activate loneliness feelings, and this activation is associated with psychological distress, including anxiety, depressive, and comorbid anxiety-depressive symptoms.

Systematic Review: Urine Biomarker Discovery for Inflammatory Bowel Disease Diagnosis.

Inflammatory bowel diseases (IBDs) are chronic, heterogeneous, and inflammatory conditions mainly affecting the gastrointestinal tract. Currently, endoscopy is the gold standard test for assessing mucosal activity and healing in clinical practice; however, it is a costly, time-consuming, invasive, and uncomfortable procedure for the patients. Therefore, there is an urgent need for sensitive, specific, fast and non-invasive biomarkers for the diagnosis of IBD in medical research. Urine is an excellent biofluid for discovering biomarkers because it is non-invasive to sample. In this review, we aimed to summarize proteomics and metabolomics studies performed in both animal models of IBD and humans that identify urinary biomarkers for IBD diagnosis. Future large-scale multi-omics studies should be conducted in collaboration with clinicians, researchers, and industry to make progress toward the development of sensitive and specific diagnostic biomarkers, thereby making personalized medicine possible.

Long Non-Coding RNA Signatures in the Ileum and Colon of Crohn's Disease Patients and Effect of Anti-TNF-α Treatment on Their Modulation.

Biological therapies only benefit one-third of patients with Crohn's disease (CD). For this reason, a deeper understanding of the mechanisms by which biologics elicit their effect on intestinal mucosa is needed. Increasing evidence points toward the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of CD, although their role remains poorly studied. We aimed to characterize lncRNA profiles in the ileum and colon from CD patients and evaluate the effect of anti-TNF-α treatment on their transcription. Terminal ileum and left colon samples from 30 patients (active CD = 10, quiescent CD = 10, and healthy controls (HCs) = 10) were collected for RNA-seq. The patients were classified according to endoscopic activity. Furthermore, biopsies were cultured with infliximab, and their transcriptome was determined by Illumina gene expression array. A total of 678 differentially expressed lncRNAs between the terminal ileum and left colon were identified in HCs, 438 in patients with quiescent CD, and 468 in patients with active CD. Additionally, we identified three new lncRNAs in the ileum associated with CD activity. No differences were observed when comparing the effect of infliximab according to intestinal location, presence of disease (CD vs. HC), and activity (active vs. quiescent). The expression profiles of lncRNAs are associated with the location of intestinal tissue, being very different in the ileum and colon. The presence of CD and disease activity are associated with the differential expression of lncRNAs. No modulatory effect of infliximab has been observed in the lncRNA transcriptome.

Development of a Prediction Model for Short-Term Remission of Patients with Crohn's Disease Treated with Anti-TNF Drugs.

Therapy with anti-tumor necrosis factor (TNF) has dramatically changed the natural history of Crohn's disease (CD). However, these drugs are not without adverse events, and up to 40% of patients could lose efficacy in the long term. We aimed to identify reliable markers of response to anti-TNF drugs in patients with CD. A consecutive cohort of 113 anti-TNF naive patients with CD was stratified according to clinical response as short-term remission (STR) or non-STR (NSTR) at 12 weeks of treatment. We compared the protein expression profiles of plasma samples in a subset of patients from both groups prior to anti-TNF therapy by SWATH proteomics. We identified 18 differentially expressed proteins (p ≤ 0.01, fold change ≥ 2.4) involved in the organization of the cytoskeleton and cell junction, hemostasis/platelet function, carbohydrate metabolism, and immune response as candidate biomarkers of STR. Among them, vinculin was one of the most deregulated proteins (p < 0.001), whose differential expression was confirmed by ELISA (p = 0.054). In the multivariate analysis, plasma vinculin levels along with basal CD Activity Index, corticosteroids induction, and bowel resection were factors predicting NSTR.

FiLaC® procedure for highly selected anal fistula patients: indications, safety and efficacy from an observational study at a tertiary referral center.

BACKGROUND: the ideal clinical profile of patients or fistula features for fistula laser closure (FiLaC®) technique remain to be established. The aim of this study was to analyze clinical outcomes and the safety profile of FiLaC® in search for an ideal setting for this technique. METHODS: a retrospective observational study was performed from a prospective database including all consecutive patients who underwent surgery for anal fistula (AF) with FiLaC® in the coloproctology unit of a tertiary referral center, between October 2015 and December 2021. The FiLaC® procedure was offered to AF patients who were considered to be at risk of fecal incontinence. Fistulas were described according to Parks' classification and categorized as complex or simple according to the American Gastroenterological Association (AGA) guidelines. Healing was defined by the closure of the internal and external openings for at least six months. Predictive factors of AF healing were investigated. RESULTS: a total of 36 patients were included, with a mean age of 48 ± 13.9 years. Twenty patients (55.6 %) were male and 13 patients (36 %) had Crohn's disease (CD). Fourteen patients (38.8 %) had a complex fistula. The primary and secondary healing rates were 55.6 % and 91.7 %, respectively, during a median follow-up time of 12 months (IQR 7-29). No fecal continence impairment was registered in any case. The proportion of patients with primary healing was significantly higher in CD patients (76.9 % vs 43.5 %, p = 0.048). CONCLUSIONS: FiLaC® is a sphincter-preserving procedure with an excellent safety profile and reasonable success rate despite of the strict patient selection. This technique may be attractive for patients with CD due to its higher primary healing rate.

Tips and tricks for successfully conducting a multicenter study. / Reglas y consejos para desarrollar con éxito un estudio multicéntrico.

Multicenter studies play a crucial role in medical research and advancement, facilitating the application of new knowledge to clinical practice. These studies are associated with multiple benefits but are more complex than those involving a single center. With the philosophy that most of the qualities required to lead a multicenter study depend on attitude and can be learned, developed, and improved, in this manuscript, we share with the reader a series of recommendations that we consider important for successfully conducting such studies. The tips and tricks that will be discussed in detail are as follows: effectively leading the project; clearly defining viable and relevant objectives; designing a clear and detailed protocol; carefully selecting centers and collaborating investigators; meticulously designing the case report form; centrally managing the project efficiently; maintaining fluent communication with investigators; and, finally, designing a clear authorship policy and ensuring the appropriate publication of the study results. We hope that these suggestions encourage potential researchers to conduct multicenter studies, thereby collectively enhancing the quality of research and its application to clinical practice.