RESUMEN
OBJECTIVES: COVID-19 has rapidly become a major health emergency worldwide. Patients with IBD are at increased risk of infection, especially when they have active disease and are taking immunosuppressive therapy. The characteristics and outcomes of COVID-19 in patients with IBD remain unclear. DESIGN: This Italian prospective observational cohort study enrolled consecutive patients with an established IBD diagnosis and confirmed COVID-19. Data regarding age, sex, IBD (type, treatments and clinical activity), other comorbidities (Charlson Comorbidity Index (CCI)), signs and symptoms of COVID-19 and therapies were compared with COVID-19 outcomes (pneumonia, hospitalisation, respiratory therapy and death). RESULTS: Between 11 and 29 March 2020, 79 patients with IBD with COVID-19 were enrolled at 24 IBD referral units. Thirty-six patients had COVID-19-related pneumonia (46%), 22 (28%) were hospitalised, 7 (9%) required non-mechanical ventilation, 9 (11%) required continuous positive airway pressure therapy, 2 (3%) had endotracheal intubation and 6 (8%) died. Four patients (6%) were diagnosed with COVID-19 while they were being hospitalised for a severe flare of IBD. Age over 65 years (p=0.03), UC diagnosis (p=0.03), IBD activity (p=0.003) and a CCI score >1 (p=0.04) were significantly associated with COVID-19 pneumonia, whereas concomitant IBD treatments were not. Age over 65 years (p=0.002), active IBD (p=0.02) and higher CCI score were significantly associated with COVID-19-related death. CONCLUSIONS: Active IBD, old age and comorbidities were associated with a negative COVID-19 outcome, whereas IBD treatments were not. Preventing acute IBD flares may avoid fatal COVID-19 in patients with IBD. Further research is needed.
Asunto(s)
Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus , Enfermedades Inflamatorias del Intestino , Pandemias , Manejo de Atención al Paciente , Neumonía Viral , Factores de Edad , COVID-19 , Comorbilidad , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/terapia , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Inmunosupresores/uso terapéutico , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/terapia , Italia/epidemiología , Masculino , Persona de Mediana Edad , Evaluación de Procesos y Resultados en Atención de Salud , Gravedad del Paciente , Manejo de Atención al Paciente/métodos , Manejo de Atención al Paciente/estadística & datos numéricos , Neumonía Viral/diagnóstico , Neumonía Viral/etiología , Neumonía Viral/mortalidad , Neumonía Viral/fisiopatología , Neumonía Viral/terapia , Estudios Prospectivos , Factores de Riesgo , SARS-CoV-2RESUMEN
BACKGROUND: The administration of biological drugs in inflammatory bowel diseases (IBD) is increasingly moving from intravenous to subcutaneous formulations. AIMS: To evaluate the efficacy and safety of vedolizumab subcutaneous administration after switching from intravenous administration in ulcerative colitis (UC) patients in corticosteroid-free clinical remission. METHODS: An observational, multicentre, prospective study was conducted by the Italian Group for the study of IBD (IG-IBD). UC patients in clinical remission (pMAYO < 2) not receiving steroids for > 8 months before the switch, and with at least 6 months of follow-up were included. Switch from intravenous to subcutaneous vedolizumab was defined as successful in patients not experiencing a disease flare (pMAYO ≥ 2) or needing oral steroids or stopping subcutaneous vedolizumab during the 6 months of follow-up after the switch. RESULTS: Overall, 168 patients were included. The switch was a success in 134 patients (79.8%). Vedolizumab retention rate was 88.7% at month six. C-reactive protein and faecal calprotectin values did not change after the switch (p = 0.07 and p = 0.28, respectively). Ten of the 19 patients who stopped subcutaneous formulation switched back to intravenous formulation recapturing clinical remission in 80%. Side effects were observed in 22 patients (13.1%). CONCLUSION: Effectiveness of switching from intravenous to subcutaneous vedolizumab formulation in UC patients in steroid-free clinical remission is confirmed in a real-world setting.
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Colitis Ulcerosa , Enfermedades Inflamatorias del Intestino , Humanos , Administración Intravenosa , Colitis Ulcerosa/tratamiento farmacológico , Fármacos Gastrointestinales , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Estudios Prospectivos , Esteroides/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND AND AIMS: The purpose of this study was to present data on the safety of anti- severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in a cohort of inflammatory bowel disease (IBD) patients of an ongoing multicenter study (ESCAPE-IBD) sponsored by the Italian Group for the study of Inflammatory Bowel Disease (ClinicalTrials.gov Identifier: NCT04769258). METHODS: Anti-SARS-CoV-2 vaccination was administrated to 809 IBD patients. Interviews were conducted to report adverse events related to vaccination. Of these 809, 346 patients were surveyed on the pandemic burden and the main reason for hesitancy in coronavirus disease 2019 vaccination. The chi-square test was used to compare categorical variables. Logistic regression was used to assess the relationship between disease-related characteristics and the onset of adverse events. RESULTS: About 45% of patients had at least one side effect, following the first dose (10%), the second (15%), and both doses (19%). All the adverse events were mild and lasted only a few days. Logistic regression analysis revealed that female sex ( P â <â 0.001), younger age ( P â =â 0.001), seroconversion ( P â =â 0.002), and comorbidity ( P â <â 0.001) were significantly associated with adverse events. The survey showed that the main concerns were the possibility of adverse event (33%). Almost all patients (99%) felt safer having been vaccinated at their IBD reference center. CONCLUSION: The vaccine reactions experienced in IBD patients were mostly self-limited. We found high acceptance and good safety of SARS-CoV-2 vaccination in our cohort.
Asunto(s)
COVID-19 , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Enfermedades Inflamatorias del Intestino , Humanos , Femenino , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Pandemias , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/epidemiología , Vacunación/efectos adversosRESUMEN
BACKGROUND AND AIMS: Restructuring activities have been necessary during the lockdown phase of the coronavirus disease 2019 (COVID-19) pandemic. Few data are available on the post-lockdown phase in terms of health-care procedures in inflammatory bowel disease (IBD) care, and no data are available specifically from IBD units. We aimed to investigate how IBD management was restructured during the lockdown phase, the impact of the restructuring on standards of care and how Italian IBD units have managed post-lockdown activities. METHODS: A web-based online survey was conducted in two phases (April and June 2020) among the Italian Group for IBD affiliated units within the entire country. We investigated preventive measures, the possibility of continuing scheduled visits/procedures/therapies because of COVID-19 and how units resumed activities in the post-lockdown phase. RESULTS: Forty-two referral centres participated from all over Italy. During the COVID-19 lockdown, 36% of first visits and 7% of follow-up visits were regularly done, while >70% of follow-up scheduled visits and 5% of first visits were done virtually. About 25% of scheduled endoscopies and bowel ultrasound scans were done. More than 80% of biological therapies were done as scheduled. Compared to the pre-lockdown situation, 95% of centres modified management of outpatient activity, 93% of endoscopies, 59% of gastrointestinal ultrasounds and 33% of biological therapies. Resumption of activities after the lockdown phase may take three to six months to normalize. Virtual clinics, implementation of IBD pathways and facilities seem to be the main factors to improve care in the future. CONCLUSION: Italian IBD unit restructuring allowed quality standards of care during the COVID-19 pandemic to be maintained. A return to normal appears to be feasible and achievable relatively quickly. Some approaches, such as virtual clinics and identified IBD pathways, represent a valid starting point to improve IBD care in the post-COVID-19 era.
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COVID-19/epidemiología , Enfermedades Inflamatorias del Intestino/epidemiología , Nivel de Atención , Vías Clínicas , Manejo de la Enfermedad , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/terapia , Italia/epidemiología , Pandemias , Vigilancia en Salud Pública , Calidad de Vida , Nivel de Atención/normas , Encuestas y CuestionariosRESUMEN
Spondyloarthritis (SpA) and inflammatory bowel disease (IBD) are chronic autoinflammatory diseases that partially share the genetic predisposition and the unchecked inflammatory response linking the gut to the joints. The coexistence of both conditions in patients and the increased cross-risk ratios between SpA and IBD strongly suggest a shared pathophysiology. The prevalence of Enteropathic-related Spondyloarthritis (ESpA) in IBD patients shows a wide variation and may be underestimated. It is well accepted that the management of joint pain requires rheumatological expertise in conjunction with gastroenterologist assessment. In this view, we aimed at assessing, in a prospective study performed in a combined Gastro-Intestinal and Rheumatologic "GI-Rhe" clinic: (1) the prevalence of ESpA and other rheumatologic diseases in IBD patients with joint pain; (2) the features of the ESpA population; and (3) the diagnostic delay and the potential impact of the combined assessment. From November 2012 to December 2014, IBD patients with joint pain referring to a dedicated rheumatologist by the IBD-dedicated gastroenterologist were enrolled. Clinical and biochemical evaluations, joint involvement and disease activity assessment, diagnostic delay, and treatment were recorded. IBD patients (n=269) with joint pain were jointly assessed in the "GI-Rhe" Unit. A diagnosis of ESpA was made in 50.5% of IBD patients with joint pain. ESpA patients showed a peripheral involvement in 53% of cases, axial in 20.6% and peripheral and axial in 26.4% of cases. ESpA patients had a higher prevalence of other autoimmune extra-intestinal manifestations and received more anti-TNF treatment compared with IBD patients. A mean diagnostic delay of 5.2 years was revealed in ESpA patients. Patients with joint disease onset in the 2002-2012 decade had reduced diagnostic delay compared with those with onset in the 1980-1990 and 1991-2001 decades. Diagnostic delay was further reduced for patients with joint onset in the last two years in conjunction with the establishment of the GI-Rhe clinic. Multidisciplinary approach improved management of rheumatic disorders in IBD patients allowing a more comprehensive care.
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Espondiloartritis/inmunología , Predisposición Genética a la Enfermedad , Humanos , Enfermedades Inflamatorias del Intestino/inmunología , Prevalencia , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/inmunología , Espondiloartritis/complicacionesRESUMEN
BACKGROUND: We aimed to prospectively assess whether endoscopic recurrence severity at 1 year in Crohn's disease is predictive of clinical recurrence within 5 years. METHODS: Clinical recurrence (Crohn's Disease Activity Index>150) was assessed yearly for 5 years in Crohn's disease patients undergoing ileo-colonic resection. At 1 year, recurrence was assessed by colonoscopy (Rutgeerts' score ≥i1 or ≥2i) and small intestine contrast ultrasonography. RESULTS: 40 patients were included (23 males, median age 39 [16-69] years). Clinical recurrence occurred within 5 years in 16 (40%) patients (years 1, 2, 3, 4, 5: 2 [5%]; 10 [25%]; 4 [10%]; 2 [5%]; 4 [10%], respectively). At 1 year, endoscopic recurrence (score≥i1) occurred in 39 (97.5%) patients (score≥i2: 33 [82.5%]). Ultrasound detected lesions compatible with recurrence in 39/40 (97.5%) patients. Endoscopic score at 1 year was correlated with clinical score at 2 years (p=0.007; r=0.41). Endoscopic score at 1 year was higher in patients with (n=10) vs without (n=30) clinical recurrence at 2 years (3 [2-4] vs 2 [0-4]; p=0.003). Higher endoscopic score (>i2) at 1 year was a risk factor for clinical recurrence within 5 years (OR=0.18; 95% CI 0.04-0.71; p=0.008). CONCLUSIONS: In Crohn's disease, severity of endoscopic recurrence at 1 year remains a predictive marker of clinical recurrence within 5 years. Small intestine contrast ultrasonography is useful for assessing 1-year recurrence.
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Colonoscopía , Enfermedad de Crohn/diagnóstico por imagen , Ultrasonografía/métodos , Adolescente , Adulto , Anciano , Colectomía , Medios de Contraste , Enfermedad de Crohn/cirugía , Femenino , Estudios de Seguimiento , Humanos , Íleon/cirugía , Masculino , Persona de Mediana Edad , Polietilenglicoles , Periodo Posoperatorio , Estudios Prospectivos , Recurrencia , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND AND AIMS: Whether inflammatory bowel disease [IBD] is associated with specific psoriasis phenotypes is undefined. In a case-control prospective study, we aimed to assess the severity and phenotype of psoriasis in IBD vs matched non-IBD controls with psoriasis [non-IBD]. METHODS: From 2011 to 2013, dermatological assessment was performed in all IBD patients showing lesions requiring characterisation. In patients with psoriasis, assessment included: presence, characteristics, and severity. Each IBD patient with psoriasis was matched [gender, ethnicity, age ± 5 years] with one non-IBD patient with psoriasis. STATISTICAL ANALYSIS: data were expressed as median [range], chi-square, Student's t test. RESULTS: Dermatological assessment was performed in 251 IBD patients [115 females, age 47 [16-85]; IBD duration 9 years [1-46]]: 158 Crohn's disease [CD] [63%], 93 ulcerative colitis [UC] [37%]. Psoriasis was detected in 62 [25%] IBD patients: 36 [58%] CD, 26 UC [42%; p = 0.44]. Clinical characteristics were comparable between IBD patients with or without psoriasis: age 50 [23-72] vs 47 [16-85]; IBD duration 9.5 [1-46] vs 9 [1-41]; p = non-significant]. The non-IBD group included 62 patients with psoriasis: 35 male; age 47 [18-75]. Mild psoriasis was more frequent in IBD vs non-IBD [87% vs 53%; p < 0.0001], whereas moderate and severe psoriasis were more frequent in non-IBD vs IBD [37% vs 13%, p = 0.004; 10% vs 0%; p = 0.036]. Plaque-type psoriasis was the most common phenotype in both IBD and non-IBD [p < 0.0001 vs others phenotypes].The frequency of plaque-type, nail psoriasis and psoriatic arthritis was lower in IBD vs non-IBD [p = 0.008; p < 0.0001; p = 0.006]. Psoriasis occurred after anti-tumour necrosis factor [TNF]α treatment in six CD patients [7%]. CONCLUSIONS: Severity and phenotypes of psoriasis may differ between patients with IBD and their matched non-IBD controls.
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Enfermedades Inflamatorias del Intestino/complicaciones , Fenotipo , Psoriasis/complicaciones , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Psoriasis/diagnóstico , Psoriasis/genética , Adulto JovenAsunto(s)
Infecciones por Coronavirus , Unidades Hospitalarias , Control de Infecciones/métodos , Enfermedades Inflamatorias del Intestino , Tamizaje Masivo/métodos , Pandemias , Neumonía Viral , Telemedicina , Cuidados Posteriores/métodos , Cuidados Posteriores/organización & administración , Betacoronavirus , COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Unidades Hospitalarias/organización & administración , Unidades Hospitalarias/estadística & datos numéricos , Unidades Hospitalarias/tendencias , Hospitalización/estadística & datos numéricos , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/terapia , Italia/epidemiología , Innovación Organizacional , Pandemias/prevención & control , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Consulta Remota/métodos , SARS-CoV-2 , Encuestas y Cuestionarios , Telemedicina/métodos , Telemedicina/organización & administraciónRESUMEN
BACKGROUND: Colonic metaplasia has been described in pouchitis. In a prospective study, we investigated whether colonic phenotype may develop in Crohn's disease (CD) ileum. The expression of sulfomucins (colonic mucin), sialomucins, and CD10 (small intestine mucin and phenotype) was evaluated before and after ileocolonic resection for CD. METHODS: From February 2007 to March 2010, 22 patients with CD undergoing surgery were enrolled. Clinical (Crohn's Disease Activity Index >150) and endoscopic recurrence (Rutgeerts score ≥1) rates were assessed at 6 and 12 months. Ileal samples were taken at surgery (T0), at 6 (T1), and 12 months (T2) for histology, histochemistry (High Iron Diamine-Alcian Blue), and immunohistochemistry (anti-CD10). RESULTS: In 22 patients, recurrence was assessed at 6 and 12 months (clinical recurrence 9% and 18%; endoscopic recurrence 73% and 77%). In all 22 patients, ileal samples were taken at 6 and 12 months (involved area in patients with recurrence). In 19 of 22 (86.3%) patients, the involved ileum was also studied at surgery. At T0, T1, and T2, the expression of sialomucins and CD10 (small intestine mucin and phenotype) was comparable and higher (P < 0.0001) than the expression of sulfomucins (colonic mucin) (mean [range], T0:82 [35-100] versus 75 [0-100] versus 16 [0-50]; T1:96 [60-100] versus 94.7 [50-100] versus 3.89 [0-40]; T2:93.3 [60-100] versus 88.1 [25-100] versus 6.6 [0-40]). The expression of small-intestine mucin and phenotype was higher at T1 (P = 0.025) versus T0 (P = 0.026). Differently, the expression of colonic mucin was lower at T1 versus T0 (P = 0.027). CONCLUSIONS: In CD, the ileum involved by severe/established lesions develops a "metaplastic" colonic mucosa phenotype. Differently, CD ileum with no lesions or with early recurrence maintains the "native" small intestine type mucin secretion and phenotype.
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Biomarcadores/metabolismo , Colon/patología , Enfermedad de Crohn/patología , Enfermedad de Crohn/cirugía , Íleon/patología , Adolescente , Adulto , Colon/metabolismo , Colon/cirugía , Colonoscopía , Enfermedad de Crohn/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Íleon/metabolismo , Íleon/cirugía , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Mucinas/metabolismo , Neprilisina/metabolismo , Fenotipo , Pronóstico , Estudios Prospectivos , Recurrencia , Factores de Riesgo , Índice de Severidad de la Enfermedad , Sialomucinas/metabolismo , Adulto JovenRESUMEN
BACKGROUND AND AIM: The use of the highly effective thiopurines as early therapeutic option in Crohn's Disease (CD) may be discouraged by the long time interval required to obtain clinical efficacy as also by their potential side effects. The development of non-invasive markers of responsiveness to thiopurines represents a major attempt in the clinical management of CD patients. Azathioprine is able to induce apoptosis of T cells. We studied the effect of thiopurines on "in vitro" T cell apoptosis, IFN-γ and IL-10 production in a group of CD patients with known response to a previous treatment with AZA. METHODS: Heparinized blood samples were drawn from 25 CD patients showing or not a previous responsiveness to a conventional azathioprine treatment (n=17 and n=8, respectively). CD4+ T cells were stimulated "in vitro" with aCD3/28 mAbs in the presence or absence of azathioprine, 6-mercaptopurine or 6-thioguanine. Apoptosis was assessed using Annexin V staining, and IFN-γ and IL-10 production in cell culture supernatants was evaluated by ELISA. RESULTS: Apoptosis stimulation index (% of apoptotic cells in the presence of thiopurine/% of apoptotic cells in the absence of thiopurine) and IFN-γ stimulation index (IFN-γ production in the presence of thiopurine/IFN-γ production in the absence of thiopurine) were, respectively, significantly lower and higher in non-responder when compared to responder patients. No variation was observed in IL-10 production. CONCLUSIONS: Evaluation of apoptosis and IFN-γ stimulation index of peripheral CD4+ T cell may be useful for a proper selection of CD patients candidate to thiopurine treatment.
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Azatioprina/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Interferón gamma/biosíntesis , Linfocitos T/patología , Adalimumab , Adolescente , Adulto , Anciano , Antiinflamatorios no Esteroideos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Apoptosis , Budesonida/uso terapéutico , Células Cultivadas , Femenino , Glucocorticoides/uso terapéutico , Humanos , Infliximab , Interleucina-10/metabolismo , Masculino , Mesalamina/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto JovenRESUMEN
BACKGROUND: The development of symptomatic strictures in Crohn's Disease after anti-Tumour Necrosis Factor-α antibodies is undefined. AIM: To assess, in a prospective longitudinal study, the frequency of sub/obstructions in Crohn's Disease patients after treatment with Infliximab or Adalimumab. Changes of small bowel lesions after these biological therapies were searched by ultrasonography. MATERIALS AND METHODS: From January 2007 to October 2008, 36 Crohn's Disease patients with no previous sub/obstructions were treated with either Infliximab (n=13) or Adalimumab (n=23) for ≥12months (mean follow-up duration after the first treatment 23.2±6.8months). Small Intestine Contrast Ultrasonography was performed before and after treatment in 19/36 patients. Sonographic parameters included: bowel wall thickness, lumen diameter, bowel dilation and lesion extent. RESULTS: Sub/obstructions developed in 3/36 patients treated with Infliximab (n=1) or Adalimumab (n=2), all with fibrostricturing Crohn's Disease. Sonographic parameters did not significantly change after treatment. CONCLUSIONS: Sub/obstructive symptoms may develop in one tenth of Crohn's Disease patients treated with anti-Tumour Necrosis Factor-α antibodies, with no significant sonographic changes of the small bowel lesions.
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Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Obstrucción Intestinal/etiología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab , Adulto , Constricción Patológica/diagnóstico por imagen , Constricción Patológica/etiología , Enfermedad de Crohn/diagnóstico por imagen , Femenino , Humanos , Infliximab , Obstrucción Intestinal/diagnóstico por imagen , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Ultrasonografía , Adulto JovenRESUMEN
BACKGROUND: Tumor necrosis factor α (TNF-α) plays a major role in the tissue-damaging immune response in inflammatory bowel diseases (IBDs). The tissue concentration of TNF-α is related to the activity of "A Disintegrin And Metalloprotease" (ADAMs), enzymes that process membrane-bound TNF-α and liberate the TNF-α trimer into the extracellular environment. Although IBD-related inflammation is associated with high ADAM17 levels, the contribution of other members of the ADAMs family is not known. In this study, we characterized the expression of other TNF-α convertases (i.e., ADAM9, ADAM10, and ADAM19) in IBD. METHODS: Normal and IBD biopsies were examined for the content of ADAMs by real-time polymerase chain reaction, Western blotting and immunohistochemistry. ADAM19 was also analyzed in intestinal epithelial cells and normal colonic explants stimulated with inflammatory cytokines and in ex vivo biopsies taken from IBD patients before and after a successful infliximab treatment. RESULTS: ADAM19 RNA transcripts and protein were upregulated in patients with ulcerative colitis and, to a lesser extent, in patients with Crohn's disease compared with normal controls. In contrast, ADAM9 and ADAM10 expression did not differ between patients with IBD and controls. Immunohistochemical analysis showed that epithelial cells were the major source of ADAM19 in IBD. ADAM19 expression was increased in colonic epithelial cell lines and normal colonic explants by TNF-α, interleukin 21 and interleukin 6, and was downregulated in IBD tissue by infliximab. CONCLUSIONS: These findings suggest the existence of a positive feedback mechanism involving cytokines and ADAM19 that can amplify cytokine production in IBD.
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Proteínas ADAM/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Colon/enzimología , Íleon/enzimología , Enfermedades Inflamatorias del Intestino/enzimología , Mucosa Intestinal/enzimología , Proteínas de la Membrana/metabolismo , Proteína ADAM10 , Antiinflamatorios no Esteroideos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Biomarcadores/metabolismo , Western Blotting , Estudios de Casos y Controles , Células Cultivadas , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/enzimología , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/enzimología , Citocinas/metabolismo , Humanos , Inmunohistoquímica , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab , Reacción en Cadena en Tiempo Real de la Polimerasa , Regulación hacia ArribaRESUMEN
BACKGROUND & AIMS: The combined role of immunomodulators (IMM) and clinical characteristics of Inflammatory Bowel Disease (IBD) in determining the cancer risk is undefined. The aim was to assess whether clinical characteristics of IBD are independent risk factors for cancer, when considering thiopurines and anti-TNFs use. METHODS: In a single-center cohort study, clinical characteristics of IBD patients with IBD duration ≥1 year and ≥2 visits from 2000 to 2009 were considered. Tests for crude rates and survival analysis methods were used to assess differences of incidence of cancer between groups. The methods were adjusted for the time interval between diagnosis and immunomodulatory treatments. RESULTS: IBD population included 1222 patients :615 Crohn's disease (CD), 607 ulcerative colitis (UC). Cancer was diagnosed in 51 patients (34 CD,17 UC), with an incidence rate of 4.3/1000 pt/year. The incidence rate of cancer was comparable between CD and UC (4.6/1000 pt/year vs 2.9/1000 pt/year ;p=n.s.). Cancer most frequently involved the breast, the GI tract, the skin. Lymphoma was diagnosed in CD (1HL, 1NHL,0 HSTCL). Risk factors for cancer included older age at diagnosis of IBD (CD: HR 1.25;95%CI 1.08-1.45; UC:HR 1.33;95%CI 1.15-1.55 for an increase by 5 years; p=0.0023; p=0.0002), fistulizing pattern in CD (HR 2.55; 95%CI 1.11-5.86,p=0.0275), pancolitis in UC (HR 2.79;95%CI 1.05-7.40 p=0.0396 vs distal). IMM and anti-TNFs did not increase the cancer risk in CD, neither IMM in UC (anti-TNFs risk in UC not feasible as no cases observed). CONCLUSIONS: Fistulizing pattern in CD, pancolitis in UC and older age at diagnosis of IBD are independent risk factors for cancer.
Asunto(s)
Colitis Ulcerosa/complicaciones , Neoplasias del Colon/etiología , Enfermedad de Crohn/complicaciones , Fístula Intestinal/complicaciones , Medición de Riesgo/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Colitis/complicaciones , Colitis/epidemiología , Colitis Ulcerosa/epidemiología , Neoplasias del Colon/epidemiología , Enfermedad de Crohn/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Fístula Intestinal/epidemiología , Italia/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Factores de Tiempo , Adulto JovenRESUMEN
AIM: To compare computed tomography enteroclysis (CTE) vs small intestine contrast ultrasonography (SICUS) for assessing small bowel lesions in Crohn's disease (CD), when using surgical pathology as gold standard. METHODS: From January 2007 to July 2008, 15 eligible patients undergoing elective resection of the distal ileum and coecum (or right colon) were prospectively enrolled. All patients were under follow-up. The study population included 6 males and 9 females, with a median age of 44 years (range: 18-80 years). INCLUSION CRITERIA: (1) certain diagnosis of small bowel requiring elective ileo-colonic resection; (2) age between 18-80 years; (3) elective surgery in our Surgical Unit; and (4) written informed consent. SICUS and CTE were performed ≤ 3 mo before surgery, followed by surgical pathology. The following small bowel lesions were blindly reported by one sonologist, radiologist, surgeon and histolopathologist: disease site, extent, strictures, abscesses, fistulae, small bowel dilation. Comparison between findings at SICUS, CTE, surgical specimens and histological examination was made by assessing the specificity, sensitivity and accuracy of each technique, when using surgical findings as gold standard. RESULTS: Among the 15 patients enrolled, CTE was not feasible in 2 patients, due to urgent surgery in one patients and to low compliance in the second patient, refusing to perform CTE due to the discomfort related to the naso-jejunal tube. The analysis for comparing CTE vs SICUS findings was therefore performed in 13 out of the 15 CD patients enrolled. Differently from CTE, SICUS was feasible in all the 15 patients enrolled. No complications were observed when using SICUS or CTE. Surgical pathology findings in the tested population included: small bowel stricture in 13 patients, small bowel dilation above ileal stricture in 10 patients, abdominal abscesses in 2 patients, enteric fistulae in 5 patients, lymphnodes enlargement (> 1 cm) in 7 patients and mesenteric enlargement in 9 patients. In order to compare findings by using SICUS, CTE, histology and surgery, characteristics of the small bowel lesions observed in CD each patient were blindly reported in the same form by one gastroenterologist-sonologist, radiologist, surgeon and anatomopathologist. At surgery, lesions related to CD were detected in the distal ileum in all 13 patients, also visualized by both SICUS and CTE in all 13 patients. Ileal lesions > 10 cm length were detected at surgery in all the 13 CD patients, confirmed by SICUS and CTE in the same 12 out of the 13 patients. When using surgical findings as a gold standard, SICUS and CTE showed the exactly same sensitivity, specificity and accuracy for detecting the presence of small bowel fistulae (accuracy 77% for both) and abscesses (accuracy 85% for both). In the tested CD population, SICUS and CTE were also quite comparable in terms of accuracy for detecting the presence of small bowel strictures (92% vs 100%), small bowel fistulae (77% for both) and small bowel dilation (85% vs 82%). CONCLUSION: In our study population, CTE and the non-invasive and radiation-free SICUS showed a comparable high accuracy for assessing small bowel lesions in CD.
Asunto(s)
Medios de Contraste , Enfermedad de Crohn/diagnóstico , Íleon/diagnóstico por imagen , Tomografía Computarizada Multidetector , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/patología , Enfermedad de Crohn/cirugía , Femenino , Humanos , Íleon/patología , Íleon/cirugía , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Ultrasonografía , Adulto JovenRESUMEN
BACKGROUND & AIMS: The diagnostic role of Small Bowel Capsule Endoscopy (SBCE) in Crohn's Disease (CD) is under investigation. In a prospective study we investigated the diagnostic role of SBCE in patients with symptoms highly compatible with CD and undefined diagnosis after conventional techniques. METHODS: From September 2005 to May 2009, all patients with clinically suspected CD and not conclusive diagnosis after Ileocolonoscopy (IC), Small Bowel Follow Through (SBFT) and Small Intestine Contrast Ultrasonography (SICUS) were enrolled. Findings compatible with CD included: bowel wall thickness (BWT) >3mm (for SICUS), ulcers, stenosis/strictures, fistulae (for SICUS, SBFT); >5 aphtoid ulcers, deep ulcers and/or strictures (for SBCE). RESULTS: Conventional techniques did not lead to a conclusive diagnosis in 30 patients (19 F, median age 31 years, range 8-57), showing chronic diarrhoea (n=27), abdominal pain (n=23), weight loss (n=5), fever (n=5), Iron Deficiency Anaemia (IDA)(n=5) and/or perianal disease (n=4). Findings compatible but not diagnostic for small bowel CD were detected in 19 (63%) by IC in 12 (40%) by SICUS and in 15 (50%) by SBFT. SBCE showed ileal lesions in 15 (50%) patients, including findings compatible with CD in 12 (40%). SBCE retention requiring surgery was observed in 1 patient. A significant concordance was observed between SBCE and IC k=0.33 C(k)=[0.25;0.42], but not between SBCE and SICUS k=0.13 IC(k)=[0.045;0.22] and between SBCE and SBFT k=0 IC(k)=[-0.089;0.089]. CONCLUSIONS: SBCE may detect lesions compatible with small bowel CD in almost one third of patients with symptoms highly compatible with CD and not conclusive diagnosis by using conventional techniques.
Asunto(s)
Endoscopía Capsular , Colonoscopía , Enfermedad de Crohn/diagnóstico , Intestino Delgado/diagnóstico por imagen , Adolescente , Adulto , Niño , Medios de Contraste , Enfermedad de Crohn/patología , Femenino , Humanos , Intestino Delgado/patología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Radiografía , Ultrasonografía , Adulto JovenRESUMEN
AIM: To investigate the prevalence of proximal small bowel (SB) lesions detected by wireless capsule endoscopy (WCE) in Crohn's disease (CD). METHODS: WCE was performed in 64 patients: 32 with CD of the distal ileum, and 32 controls with iron-deficiency anemia (IDA) or diarrhea. WCE was performed using the Given SB-WCE, followed by small intestine contrast ultrasonography (SICUS). Findings compatible with CD by using WCE included erosions, aphthoid or deep ulcers, and strictures/stenosis. RESULTS: WCE detected proximal SB lesions in 16/32 (50%) patients (14 aphthoid ulcers, 2 deep ulcers, one stricture), which appeared not to be related to clinical parameters [epigastric pain, age, smoking, non-steroidal anti-inflammatory drugs (NSAIDs), IDA]. Among patients with proximal SB lesions, 6 (37%) were smokers, 3 (19%) NSAID users, 3 (19%) had epigastric pain and 4 (25%) had IDA. SICUS detected proximal SB lesions in 3/32 patients (19%) also showing lesions with WCE. No correlations were observed between proximal SB lesions assessed by WCE or by SICUS (chi(2) = 1.5, P = 0.2). CONCLUSION: The use of WCE allows the detection of previously unknown upper SB lesions in a high proportion of patients with a previous diagnosis of CD involving the distal ileum.