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1.
Neurobiol Dis ; 192: 106416, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38272141

RESUMEN

BACKGROUND: The dysregulation of the gut-brain axis in chronic inflammatory bowel diseases can cause neuro-psychological disturbances, but the underlying mechanisms are still not fully understood. The choroid plexus (CP) maintains brain homeostasis and nourishment through the secretion and clearance of cerebrospinal fluid. Recent research has demonstrated the existence of a CP vascular barrier in mice which is modulated during intestinal inflammation. This study investigates possible correlations between CP modifications and inflammatory activity in patients with Crohn's disease (CD). METHODS: In this prospective study, 17 patients with CD underwent concomitant abdominal and brain 3 T MRI. The volume and permeability of CP were compared with levels of C-reactive protein (CRP), fecal calprotectin (FC), sMARIA and SES-CD scores. RESULTS: The CP volume was negatively correlated with CRP levels (R = -0.643, p-value = 0.024) and FC (R = -0.571, p-value = 0.050). DCE metrics normalized by CP volume were positively correlated with CRP (K-trans: R = 0.587, p-value = 0.045; Vp: R = 0.706, p-value = 0.010; T1: R = 0.699, p-value = 0.011), and FC (Vp: R = 0.606, p-value = 0.037). CONCLUSIONS: Inflammatory activity in patients with CD is associated with changes in CP volume and permeability, thus supporting the hypothesis that intestinal inflammation could affect the brain through the modulation of CP vascular barrier also in humans.


Asunto(s)
Enfermedad de Crohn , Humanos , Animales , Ratones , Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/metabolismo , Plexo Coroideo/diagnóstico por imagen , Plexo Coroideo/metabolismo , Estudios Prospectivos , Eje Cerebro-Intestino , Biomarcadores/metabolismo , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Complejo de Antígeno L1 de Leucocito/metabolismo , Índice de Severidad de la Enfermedad , Inflamación/diagnóstico por imagen , Permeabilidad
2.
Eur J Clin Invest ; : e14283, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38979834

RESUMEN

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.

3.
Gut ; 72(10): 1838-1847, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-36788014

RESUMEN

OBJECTIVES: Ulcerative colitis (UC) is a chronic inflammatory disorder of unknown aetiology. Gut virome dysbiosis is fundamental in UC progression, although its role in the early phases of the disease is far from fully understood. Therefore, we sought to investigate the role of a virome-associated protein encoded by the Orthohepadnavirus genus, the hepatitis B virus X protein (HBx), in UC aetiopathogenesis. DESIGN: HBx positivity of UC patient-derived blood and gut mucosa was assessed by RT-PCR and Sanger sequencing and correlated with clinical characteristics by multivariate analysis. Transcriptomics was performed on HBx-overexpressing endoscopic biopsies from healthy donors.C57BL/6 mice underwent intramucosal injections of liposome-conjugated HBx-encoding plasmids or the control, with or without antibiotic treatment. Multidimensional flow cytometry analysis was performed on colonic samples from HBx-treated and control animals. Transepithelial electrical resistance measurement, proliferation assay, chromatin immunoprecipitation assay with sequencing and RNA-sequencing were performed on in vitro models of the gut barrier. HBx-silencing experiments were performed in vitro and in vivo. RESULTS: HBx was detected in about 45% of patients with UC and found to induce colonic inflammation in mice, while its silencing reverted the colitis phenotype in vivo. HBx acted as a transcriptional regulator in epithelial cells, provoking barrier leakage and altering both innate and adaptive mucosal immunity ex vivo and in vivo. CONCLUSION: This study described HBx as a contributor to the UC pathogenesis and provides a new perspective on the virome as a target for tailored treatments.


Asunto(s)
Colitis Ulcerosa , Colitis , Animales , Ratones , Colitis Ulcerosa/patología , Viroma , Ratones Endogámicos C57BL , Colon/patología , Colitis/metabolismo , Inflamación/metabolismo , Mucosa Intestinal/metabolismo , Modelos Animales de Enfermedad , Sulfato de Dextran
4.
Clin Gastroenterol Hepatol ; 21(12): 3143-3151, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-36521739

RESUMEN

BACKGROUND & AIMS: Colonoscopy (CS) is the gold standard to assess postoperative recurrence (POR) in Crohn's disease (CD). However, CS is invasive and may be poorly tolerated by patients. The aim of this study was to prospectively assess the diagnostic accuracy of a noninvasive approach in detecting POR, using the endoscopic Rutgeerts' score (RS) as the reference standard. METHODS: Consecutive patients with CD who underwent ileo-cecal resection were prospectively enrolled in 3 referral Italian centers. Patients underwent CS and bowel ultrasound within 1 year of surgery. Uni- and multivariable analyses were used to assess the correlation between noninvasive parameters and endoscopic recurrence, defined by a RS ≥2. RESULTS: Ninety-one patients were enrolled. Sixty patients (66%) experienced endoscopic POR. The multivariable analysis identified bowel wall thickness (BWT) per 1-mm increase (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.21-4.89; P = .012), the presence of mesenteric lymph nodes (OR, 15.63; 95% CI, 1.48-164.54; P = .022), and fecal calprotectin (FC) values ≥50 mcg/g (OR, 8.58; 95% CI, 2.45-29.99; P < .001) as independent predictors for endoscopic recurrence. The presence of lymph nodes or the combination of BWT ≥3 mm and FC values ≥50 mcg/g correctly classified 56% and 75% of patients, with less than 5% of patients falsely classified as having endoscopic recurrence. Conversely, the combination of BWT <3 mm and FC <50 mcg/g correctly classified 74% of patients with only 4.5% of patients falsely classified as not having endoscopic recurrence. CONCLUSIONS: A noninvasive approach combining bowel ultrasound and FC can be used with confidence for detecting POR in patients with CD without the requirement for CS.


Asunto(s)
Enfermedad de Crohn , Humanos , Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/cirugía , Estudios Prospectivos , Biomarcadores/análisis , Colonoscopía , Colon/patología , Recurrencia , Complejo de Antígeno L1 de Leucocito , Heces/química
5.
Clin Gastroenterol Hepatol ; 20(4): e723-e740, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-33895360

RESUMEN

BACKGROUND & AIMS: Mucosal healing is associated with better outcomes in Crohn's disease (CD). Colonoscopy is invasive and poorly tolerated. Bowel ultrasound (US) is a noninvasive tool that increasingly is being used for CD assessment. We assessed the predictive role of baseline bowel US findings on disease course in a large prospective cohort of CD patients for 12 months. METHODS: Ileocolonic CD consecutive patients were followed up for 12 months after performing bowel US. The negative course of CD, defined as the need for steroids and/or change of therapy and/or hospitalization and/or the need for surgery, was assessed. We evaluated this composite end point and subsequently considered each individual end point separately. Predictors of negative disease course were analyzed by logistic regression analysis. RESULTS: There were 225 ileal and/or colonic CD consecutive patients included in the study. We analyzed the association between baseline bowel US parameters and endoscopic activity (defined as a Simplified Endoscopic Activity score for CD > 2) to set up a noninvasive quantitative ultrasound-based score (bowel ultrasound score). The multivariable analysis identified the following independent predictors of a worse outcome throughout the 12-month period as follows: bowel ultrasound score greater than 3.52 (odds ratio [OR], 6.97; 95% CI, 2.87-16.93; P < .001), presence of at least 1 disease complication (stricture, fistula, abscess) at baseline bowel US (OR, 3.90; 95% CI, 1.21-12.53; P = .021), fecal calprotectin value of 250 µg/g or greater at baseline (OR, 5.43; 95% CI, 2.25-13.11; P < .001), and male sex (OR, 2.60; 95% CI, 1.12-6.02; P = .025). CONCLUSIONS: Bowel US predicts the 12-month course in CD.


Asunto(s)
Enfermedad de Crohn , Ultrasonografía , Enfermedad de Crohn/diagnóstico por imagen , Heces , Humanos , Intestinos , Complejo de Antígeno L1 de Leucocito , Masculino , Estudios Prospectivos , Índice de Severidad de la Enfermedad
6.
Gastrointest Endosc ; 96(1): 73-83, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35182574

RESUMEN

BACKGROUND AND AIMS: Endoscopic and histologic remission (HR) are key therapeutic targets in the management of ulcerative colitis (UC). The aim of this study was to evaluate the reproducibility of the Paddington International virtual ChromoendoScopy ScOre (PICaSSO), a virtual chromoendoscopy score originally validated by use of the iSCAN platform, with the narrow-band imaging (NBI), linked-color imaging (LCI), and blue-laser imaging (BLI) platforms. METHODS: We evaluated endoscopic activity using the Mayo Endoscopic Score (MES), the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and PICaSSO in 159 UC patients (78 NBI and 81 BLI/LCI) who underwent colonoscopy in 2 tertiary referral centers. HR was defined by the Robarts Histopathology Index (RHI) and the Nancy Histologic Index (NHI). Receiver operating characteristic curves were plotted to evaluate endoscopic scores for the prediction of HR. Intraclass correlation coefficients (ICC) between endoscopists were evaluated. RESULTS: PICaSSO had an ICC of 0.825 when the NBI and BLI/LCI cohorts were combined, higher than MES and UCEIS. The correlation between PICaSSO and RHI and NHI was 0.83 and 0.79 in the NBI cohort and between 0.63 and 0.65 in LCI/BLI. In the NBI cohort, the accuracy of MES, UCEIS, and PICaSSO was 0.936, 0.897, and 0.808 for HR measured by RHI and 0.897, 0.885, and 0.821 by NHI, respectively. In the BLI/LCI cohort, the accuracy of MES, UCEIS, LCI PICaSSO and BLI PICaSSO was 0.765, 0.778, 0.827, and 0.79 to predict HR with RHI and NHI, respectively. CONCLUSIONS: The PICaSSO score can be consistently and accurately reproduced with NBI and LCI/BLI and therefore can be applied to all virtual electronic chromoendoscopy platforms.


Asunto(s)
Colitis Ulcerosa , Colitis Ulcerosa/patología , Colonoscopía/métodos , Electrónica , Humanos , Estudios Prospectivos , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad
7.
Clin Gastroenterol Hepatol ; 18(9): 2134-2135, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32360811

RESUMEN

The first cases of COVID-19 infection were reported in December, 2019, in Wuhan, China. Italy (in particular Lombardy) and France (in particular Northeast) have been gravely hit. Both physicians and inflammatory bowel disease (IBD) patients are deeply concerned that immunosuppressants or biologics may increase the risk of COVID-19 infection. IOIBD has put in place an international registry, SECURE-IBD, for tracking all the cases with IBDs infected by COVID-19 (SECURE-IBD registry: http://www.covidibd.org). It will describe the outcomes of infected patients and the association between IBD-related medications and these outcomes.


Asunto(s)
Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/epidemiología , Enfermedades Inflamatorias del Intestino/complicaciones , Neumonía Viral/epidemiología , COVID-19 , Francia/epidemiología , Humanos , Huésped Inmunocomprometido , Incidencia , Italia/epidemiología , Pandemias , Sistema de Registros/estadística & datos numéricos , SARS-CoV-2
8.
Clin Gastroenterol Hepatol ; 18(8): 1882-1883, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32304737

RESUMEN

Since February 20, 2020, the SARS-COV2 infection has spread in Lombardy, and in the rest of the Italian regions, forcing our government to impose a national lockdown.1 Hospitals have been forced to adapt and to restructure their units to cope with this urgent new critical situation.2 Alternative solutions have been found to manage patients with inflammatory bowel disease (IBD), including remote monitoring, drug home delivery, limitations for infusion units, and patient education on measures to prevent infection,3 to maintain high-quality care.4.


Asunto(s)
Enfermedades Inflamatorias del Intestino/epidemiología , Telemedicina , Betacoronavirus , COVID-19 , Infecciones por Coronavirus , Humanos , Italia , Pandemias , Neumonía Viral , SARS-CoV-2 , Nivel de Atención
9.
Am J Gastroenterol ; 115(10): 1719-1721, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32852334

RESUMEN

INTRODUCTION: The risk of coronavirus disease-19 infection for healthcare professionals and patients in hospitals remains unclear. METHODS: We investigated whether precautions adopted in our inflammatory bowel disease (IBD) unit have minimized the risks of infection for all patients accessing our facilities in a 1-month period by assessing the rate of coronavirus disease-19 infection in the follow-up period. RESULTS: Three hundred-twenty patients with IBD were included. None were infected from severe acute respiratory syndrome-coronavirus 2 in the follow-up period. None of the IBD team members were infected. DISCUSSION: Neither pharmacological immunosuppression nor access to the hospital seem to be risk factors for infection in patients with IBD.


Asunto(s)
Infecciones por Coronavirus/prevención & control , Unidades Hospitalarias/estadística & datos numéricos , Inmunosupresores/efectos adversos , Control de Infecciones/estadística & datos numéricos , Enfermedades Inflamatorias del Intestino/inmunología , Pandemias/prevención & control , Neumonía Viral/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Betacoronavirus/inmunología , COVID-19 , Prueba de COVID-19 , Técnicas de Laboratorio Clínico/estadística & datos numéricos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Estudios de Seguimiento , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Humanos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/estadística & datos numéricos , Transmisión de Enfermedad Infecciosa de Profesional a Paciente/prevención & control , Transmisión de Enfermedad Infecciosa de Profesional a Paciente/estadística & datos numéricos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Italia/epidemiología , Persona de Mediana Edad , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , Factores de Riesgo , SARS-CoV-2 , Adulto Joven
10.
Gut ; 68(3): 562-572, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30580249

RESUMEN

Endoscopic assessment of inflammation and mucosal healing is crucial for appropriate management in IBD. Current definition of endoscopic mucosal healing has been derived using previous generation of standard white light endoscopes. New endoscopy technologies widely available provide much more detailed images of mucosal and vascular patterns. Novel endoscopic techniques with high definition image, optical and digital enhancement have enhanced the quality and fine details of vascular and mucosal pattern so that endoscopic images have started to reflect histological changes for lesions and inflammation/healing. These technologies can now define subtle inflammatory changes and increase detection and characterisation of colonic lesions in patients with IBD. The best endoscopic technique to detect dysplasia in IBD is still debated. Dye chromoendoscopy with targeted biopsies is considered by Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in inflammatory Bowel Disease Patients: International Consensus Recommendations (SCENIC consensus the standard of care and recommended for adoption by gastroenterologists in practice. In future, it is possible that well-trained colonoscopists using high definition equipment with image enhancements may be able to obtain equivalent yield without pan-colonic dye spraying and characterise lesions. Finally, SCENIC introduced endoscopic resectability of some dysplastic colonic lesions-new techniques may now better characterise endoscopic resectability and limit the number of colectomies. In this review, we will provide a state-of-the-art opinion on the direction of technological advances in the assessment of IBD and how new concepts will refine clinical practice.


Asunto(s)
Colonoscopía/métodos , Enfermedades Inflamatorias del Intestino/diagnóstico , Colonoscopía/tendencias , Colorantes , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/patología , Enfermedad de Crohn/cirugía , Humanos , Aumento de la Imagen/métodos , Enfermedades Inflamatorias del Intestino/patología , Enfermedades Inflamatorias del Intestino/fisiopatología , Enfermedades Inflamatorias del Intestino/cirugía , Mucosa Intestinal/fisiología , Cicatrización de Heridas
11.
Gastroenterology ; 153(5): 1363-1377.e6, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28827082

RESUMEN

BACKGROUND & AIMS: Alterations in signaling pathways that regulate resolution of inflammation (resolving pathways) contribute to pathogenesis of ulcerative colitis (UC). The resolution process is regulated by lipid mediators, such as those derived from the ω-3 docosahexaenoic acid (DHA), whose esterified form is transported by the major facilitator superfamily domain containing 2A (MFSD2A) through the endothelium of brain, retina, and placenta. We investigated if and how MFSD2A regulates lipid metabolism of gut endothelial cells to promote resolution of intestinal inflammation. METHODS: We performed lipidomic and functional analyses of MFSD2A in mucosal biopsies and primary human intestinal microvascular endothelial cells (HIMECs) isolated from surgical specimens from patients with active, resolving UC and healthy individuals without UC (controls). MFSD2A was knocked down in HIMECs with small hairpin RNAs or overexpressed from a lentiviral vector. Human circulating endothelial progenitor cells that overexpress MFSD2A were transferred to CD1 nude mice with dextran sodium sulfate-induced colitis, with or without oral administration of DHA. RESULTS: Colonic biopsies from patients with UC had reduced levels of inflammation-resolving DHA-derived epoxy metabolites compared to healthy colon tissues or tissues with resolution of inflammation. Production of these metabolites by HIMECs required MFSD2A, which is required for DHA retention and metabolism in the gut vasculature. In mice with colitis, transplanted endothelial progenitor cells that overexpressed MFSD2A not only localized to the inflamed mucosa but also restored the ability of the endothelium to resolve intestinal inflammation, compared with mice with colitis that did not receive MFSD2A-overexpressing endothelial progenitors. CONCLUSIONS: Levels of DHA-derived epoxides are lower in colon tissues from patients with UC than healthy and resolving mucosa. Production of these metabolites by gut endothelium requires MFSD2A; endothelial progenitor cells that overexpress MFSD2A reduce colitis in mice. This pathway might be induced to resolve intestinal inflammation in patients with colitis.


Asunto(s)
Colitis/prevención & control , Colon/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Células Progenitoras Endoteliales/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Animales , Células Cultivadas , Colitis/inducido químicamente , Colitis/genética , Colitis/metabolismo , Colon/efectos de los fármacos , Colon/patología , Sistema Enzimático del Citocromo P-450/metabolismo , Sulfato de Dextran , Modelos Animales de Enfermedad , Ácidos Docosahexaenoicos/farmacología , Células Progenitoras Endoteliales/efectos de los fármacos , Células Progenitoras Endoteliales/patología , Células Progenitoras Endoteliales/trasplante , Compuestos Epoxi/metabolismo , Humanos , Proteínas de Transporte de Membrana/genética , Ratones Desnudos , Oxilipinas/metabolismo , Interferencia de ARN , Transducción de Señal , Simportadores , Transfección , Factor de Necrosis Tumoral alfa/farmacología , Proteínas Supresoras de Tumor/genética
13.
Liver Int ; 37(1): 141-147, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27375263

RESUMEN

BACKGROUND & AIMS: Excessive intestinal gas and liver steatosis are frequent sonographic findings. Both of these appear to be caused by variations of the gut microflora. We assessed the relationship between ultrasonographic detection of intestinal gas and liver steatosis. METHODS: This study included 204 consecutive patients (99 male; mean age 53.0 ± 15.6 years), who underwent ultrasonography for abdominal complaints or follow-up of benign lesions. Body mass index, biochemical liver markers, sonographic presence of liver steatosis and/or degree of intestinal gas interfering with the examination were collected. Both sonographic findings were assessed based on standardized criteria. The association between liver steatosis and intestinal gas was evaluated by means of univariate and multivariate analyses. RESULTS: Eighty (39.2%) of patients showed moderate to large amounts of gas preventing an accurate evaluation of the liver or pancreas and 90 (44.1%) had liver steatosis. A significant correlation between the degree of intestinal gas and liver steatosis both in obese (r=.603; P<.001) and in nonobese patients (r=.555; P<.001) was found. Univariate analysis showed that intestinal gas, body mass index, aspartate transaminase, alanine transaminase, gamma-GT, age and sex were predictors of liver steatosis; only intestinal gas (OR 7.4; 95% CI 3.4-16.1) and body mass index (OR; 1.4, 95% CI 1.2-1.5), however, were independent predictors at multivariate analysis. The presence of excessive gas was also significantly correlated with liver steatosis coupled with elevated ALT (P = .001). CONCLUSION: This study shows a significant correlation between excessive intestinal gas and liver steatosis. The reasons of this finding and its clinical implications remain to be defined.


Asunto(s)
Hígado Graso/fisiopatología , Flatulencia/fisiopatología , Hígado/fisiopatología , Obesidad/complicaciones , Adulto , Anciano , Índice de Masa Corporal , Hígado Graso/diagnóstico por imagen , Femenino , Flatulencia/diagnóstico por imagen , Motilidad Gastrointestinal , Humanos , Italia , Hígado/diagnóstico por imagen , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Ultrasonografía , gamma-Glutamiltransferasa/metabolismo
14.
Digestion ; 96(3): 166-172, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28903094

RESUMEN

BACKGROUND: Most Crohn's disease (CD) patients develop endoscopic recurrence within one year of intestinal resection. The best treatment method to prevent post-operative CD recurrence remains uncertain. METHODS: A total of 155 CD patients from 2 referral centres, who were undergoing intestinal resection with ileo-colonic anastomosis (January 2004-January 2015), were included. All subjects received preventive therapy with tumour necrosis factor antagonists (anti-TNFs), thiopurinesor mesalazine. The primary outcome was the rate of endoscopic recurrence (Rutgeerts score ≥i2) in the 3 treatment groups. RESULTS: Patients treated with anti-TNFs were at significantly lower risk of endoscopic recurrence during the follow-up than those receiving thiopurines or mesalazine (incidence rates of 2.2, 3.0 and 4.8 per 100 person-months, respectively, log-rank, p = 0.011). The median time to recurrence was significantly longer in patients treated with anti-TNFs than in those who received thiopurines or mesalazine (37.0, 13.7, and 16.8 months, respectively, log-rank, p = 0.011). Anti-TNFs were more effective than mesalazine (univariable analysis, hazard ratio [HR] 0.45, 95% CI 0.26-0.77, p = 0.004; multivariable analysis, HR 0.45, 95% CI 0.26-0.77, p = 0.004), and non-significantly superior over thiopurines. CONCLUSION: Anti-TNF therapy was the most effective strategy for the prevention of endoscopic CD recurrence.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Enfermedad de Crohn/terapia , Inmunosupresores/uso terapéutico , Mercaptopurina/uso terapéutico , Mesalamina/uso terapéutico , Prevención Secundaria/métodos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Colectomía/métodos , Colonoscopía , Enfermedad de Crohn/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Modelos de Riesgos Proporcionales , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento
15.
Clin Gastroenterol Hepatol ; 14(10): 1426-1432.e1, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27317850

RESUMEN

BACKGROUND & AIMS: Infliximab is a safe and effective therapy for ulcerative colitis (UC). We conducted a multicenter retrospective cohort study that included 7 European countries and Israel to examine whether infliximab discontinuation can be considered for patients who achieve sustained remission. METHODS: We performed a retrospective cohort study, collecting medical records from 13 tertiary care referral inflammatory bowel disease centers of all patients with UC treated with infliximab (n = 193). We compared the disease course of patients with at least 12 months of clinical remission who discontinued infliximab (n = 111) with that of patients who continued scheduled treatment (controls, n = 82). We examined the incidence rates of relapse, hospitalization and colectomy, the comparative effectiveness of different therapeutic strategies after discontinuation, and assessed the rates of response, remission, and adverse effects after infliximab re-initiation. Statistical analyses used time-to-event methods. RESULTS: In the entire cohort, 67 patients (34.7%) relapsed during the follow-up period. The incidence rate of relapse was significantly higher after discontinuation (23.3 per 100 person-years) compared with the control group (7.2 per 100 person-years) in univariable analysis (log-rank P < .001; hazard ratio, 3.41; 95% confidence interval, 1.88-6.20) and multivariable analysis (hazard ratio, 3.70; 95% confidence interval, 2.02-6.77). Rates of hospitalization and colectomy did not differ between groups. Thiopurines appeared to be the best treatment option after infliximab discontinuation (incidence of relapse: 15.0 per 100 person-years for thiopurines, 27.4 per 100 person-years for thiopurines plus aminosalicylates, and 31.2 per 100 person-years for aminosalicylates alone; log-rank P = .032). Response was regained in 77.1% of patients and remission in 51.4% of patients who re-initiated infliximab. However, 17.1% had infusion reactions and 17.1% reported other adverse events. CONCLUSIONS: In a multinational retrospective cohort study of patients with UC in sustained clinical remission, we associated discontinuation of infliximab with an increased risk of relapse. Treatment re-initiation is effective and safe.


Asunto(s)
Colitis Ulcerosa/tratamiento farmacológico , Fármacos Gastrointestinales/administración & dosificación , Infliximab/administración & dosificación , Privación de Tratamiento , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Europa (Continente) , Femenino , Humanos , Israel , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Medición de Riesgo , Adulto Joven
17.
Int J Colorectal Dis ; 29(10): 1285-90, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24986138

RESUMEN

BACKGROUND AND AIM: Crohn's disease is a life-long inflammatory disease which can impair quality of life, in particular in patients with psychiatric co-morbidities such as depression and anxiety. The aim of this prospective cohort study was to assess the prevalence of depression and anxiety and related risk factors in patients with quiescent Crohn's disease. METHODS: A consecutive series of adult patients with confirmed diagnosis of Crohn's disease, in clinical remission, were included and investigated during ambulatory visits using a standard questionnaire assessing demographic and clinical features of the disease. Within 1 month after the ambulatory visit, all patients were interviewed by phone to assess the presence of psychiatric disorders using standardized questionnaires. The questionnaire assessed the development of psychiatric disorders after the diagnosis of Crohn's disease, the use of antidepressant or antianxiety therapy and current anxiety or depression by means of the Hospital Anxiety and Depression Scale. RESULTS: One hundred and ninety-five patients were included. Seventy-two (36.9 %) patients showed anxiety and/or depression symptoms, 46 (23.6 %) patients showed anxiety symptoms, 6 (3.1 %) patients showed depression symptoms and 20 (10.3 %) patients showed both symptoms. Forty-eight of these patients (58 %) were without any antidepressive or antianxiety treatment. Anxiety with or without depression was significantly correlated with female sex (p = 0.017), history of perianal disease (p = 0.003) and perianal surgery (p = 0.042). CONCLUSION: Anxiety is a frequent, often untreated, condition in patient affected by Crohn's disease in clinical remission. Female sex, history of perianal disease and perianal surgery are major risk factors for anxiety.


Asunto(s)
Ansiedad/epidemiología , Enfermedad de Crohn/psicología , Depresión/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ansiolíticos/uso terapéutico , Antidepresivos/uso terapéutico , Ansiedad/tratamiento farmacológico , Comorbilidad , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/epidemiología , Depresión/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Calidad de Vida , Fístula Rectal/complicaciones , Fístula Rectal/psicología , Inducción de Remisión , Factores de Riesgo , Factores Sexuales , Adulto Joven
18.
J Gastroenterol ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38980426

RESUMEN

BACKGROUND: Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), continues to challenge treatment paradigms. Advancements in therapeutic options have been have been driven by Phase 2 and 3 clinical trials of new drug classes, particularly sphingosine-1-phosphate (S1P) modulators and interleukin-23 (IL-23) inhibitors. METHODS: This review synthesizes findings from Phase 2 and 3 clinical trials conducted up to early 2024, focusing on the impact of S1P modulators and IL-23 inhibitors on IBD management. Drugs such as ozanimod, etrasimod, risankizumab, mirikizumab, guselkumab, and brasikumab were evaluated for their efficacy and safety profiles. RESULTS: S1P modulators, such as ozanimod and etrasimod, effectively regulate immune cell trafficking to reduce inflammation and several trials highlight their clinical effectiveness in both inducing and maintaining remission in IBD, highlighting its long-term safety and sustained therapeutic effects. Additionally, IL-23 inhibitors including risankizumab, mirikizumab, and guselkumab, which disrupt key inflammatory cytokine pathways, have already shown significant effectiveness in inducing and maintaining remission in both CD and UC, with favorable safety profiles across multiple studies, suggesting their potential as critical components in managing IBD. CONCLUSIONS: The clinical trials indicate that both S1P modulators and IL-23 inhibitors offer promising therapeutic benefits and maintain strong safety profiles, positioning them as potential cornerstone treatments for IBD. Despite these advancements, further exploration into long-term safety and the development of personalized treatment strategies is essential for maximizing clinical outcomes.

19.
Diagnostics (Basel) ; 14(14)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39061667

RESUMEN

Chronic inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, present diagnostic challenges due to their complex and heterogeneous nature. While histology remains fundamental for accurate diagnosis, a multidisciplinary approach incorporating clinical, endoscopic, and imaging modalities is increasingly recognized as essential for comprehensive evaluation. This article delves into the importance of integrating various diagnostic techniques in the assessment of IBD. Colonoscopy and histology, with its ability to directly visualize the intestinal mucosa, play a central role in the diagnostic process. However, histological analysis alone may not suffice, necessitating the inclusion of advanced imaging techniques, such as magnetic resonance enterography (MRE), computed tomography enterography (CTE), and intestinal ultrasound (IUS). These techniques provide valuable insights into the disease's extent, severity, and complications, and should be used in conjunction with biochemical parameters. These modalities complement traditional endoscopic and histological findings, offering a more holistic understanding of the disease process. A multidisciplinary approach that incorporates clinical, endoscopic, histological, serological, and imaging assessments enables clinicians to achieve a more accurate and timely diagnosis of IBD. Moreover, this integrated approach facilitates personalized treatment strategies tailored to individual patient needs, ultimately improving clinical outcomes and quality of life for those affected by chronic inflammatory bowel diseases.

20.
Immunotherapy ; 16(9): 581-595, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38629330

RESUMEN

Risankizumab is a humanized monoclonal antibody that inhibits the p19 subunit of IL-23 cytokine. Recently it has been approved for the treatment of patients with moderate-to-severe Crohn's disease (CD). We conducted a scoping review to summarize the available data on risankizumab and to define its positioning in the treatment algorithm of CD. Pubmed, Embase and Scopus databases were searched up to Oct 31, 2023 to identify studies reporting efficacy and safety data of risankizumab in patients with CD. Risankizumab is an effective and safe drug for the management of patients with moderate-to-severe CD. It could be used as first-line therapy in biologic-naive patients and in patients who have previously failed other biological therapies.


When we eat the food is processed and absorbed by the gastrointestinal tract. Sometimes, in some people, the gastrointestinal tract gets inflamed, causing problems like tummy ache and diarrhea: this condition is called Crohn's disease. To help turn off this inflammation and make people with Crohn's disease feel better, there's a new treatment called risankizumab. Risankizumab binds to the proteins in the body that cause inflammation and blocks their effects. This helps to reduce gastrointestinal inflammation and relieve its symptoms. Scientific studies have shown that is effective, safe, and it starts working quickly. Patients using this treatment do not have to go to the hospital every time. After three times in the outpatient's clinic, they can continue the treatment comfortably at home using a small device that sticks to the body and administers the medicine.


Asunto(s)
Algoritmos , Enfermedad de Crohn , Humanos , Enfermedad de Crohn/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Índice de Severidad de la Enfermedad , Subunidad p19 de la Interleucina-23/antagonistas & inhibidores , Subunidad p19 de la Interleucina-23/inmunología , Resultado del Tratamiento
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