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BACKGROUND & AIM: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF)α biologics, are at high risk for vaccine-preventable infections. Their ability to mount adequate vaccine responses is unclear. The aim of the study was to assess serologic responses to messenger RNA-Coronavirus Disease 2019 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared with healthy controls (HCs). METHODS: Prospective, controlled, multicenter Israeli study. Subjects enrolled received 2 BNT162b2 (Pfizer/BioNTech) doses. Anti-spike antibody levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinally. RESULTS: Overall, 258 subjects: 185 IBD (67 treated with anti-TNFα, 118 non-anti-TNFα), and 73 HCs. After the first vaccine dose, all HCs were seropositive, whereas â¼7% of patients with IBD, regardless of treatment, remained seronegative. After the second dose, all subjects were seropositive, however anti-spike levels were significantly lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (both P < .001). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (P < .03; P < .0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-spike levels. Infection rate (â¼2%) and AEs were comparable in all groups. IBD activity was unaffected by BNT162b2. CONCLUSIONS: In this prospective study in patients with IBD stratified according to treatment, all patients mounted serologic response to 2 doses of BNT162b2; however, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine serologic response longevity in this group may be limited, vaccine booster dose should be considered.
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Vacuna BNT162/inmunología , COVID-19/prevención & control , Inmunogenicidad Vacunal/efectos de los fármacos , Enfermedades Inflamatorias del Intestino/inmunología , Inhibidores del Factor de Necrosis Tumoral/inmunología , Adulto , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Estudios de Casos y Controles , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Israel , Masculino , Persona de Mediana Edad , Estudios Prospectivos , SARS-CoV-2/inmunologíaRESUMEN
INTRODUCTION: Whether fecal calprotectin (FC) and quality of life (QoL) questionnaires reflect change in disease activity in patients with a J-pouch is unknown. METHODS: Patients with acute pouchitis were prospectively treated with a 2-week course of antibiotics. The full Pouchitis Disease Activity Index, FC, and QoL questionnaires were measured at baseline and after antibiotic therapy. RESULTS: Twenty patients were prospectively enrolled. After 2 weeks of antibiotic treatment, the Pouchitis Disease Activity Index decreased from a median of 9 to 5 ( P = 0.007). FC decreased from a median of 661 ug/g to 294 ug/g ( P = 0.02), and QoL questionnaires improved significantly. DISCUSSION: FC and QoL questionnaires reflect real-time changes in inflammatory pouch activity.
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Colitis Ulcerosa , Reservoritis , Humanos , Reservoritis/tratamiento farmacológico , Calidad de Vida , Estudios Prospectivos , Complejo de Antígeno L1 de Leucocito , Antibacterianos/uso terapéutico , Heces , Colitis Ulcerosa/tratamiento farmacológicoRESUMEN
GOAL: The aim was to assess proactive specialized inflammatory bowel diseases (IBD) emergency department (ED) consultation and multidisciplinary IBD team (IBD-MDT) intervention on IBD-related patient outcomes after discharge. BACKGROUND: Despite advances in patient care, IBD-related ED visits have increased and substantially contribute to the IBD burden. METHODS: Consecutive patients with IBD (below 50 y) who visited the ED during November 2017 to April 2018 (intervention group) were compared with patients with IBD that visited the same ED during 2014 to 2017 (standard-care group). The primary outcomes were hospitalization and ED revisits at 30, 90, and 180 days. RESULTS: The intervention group (45 patients, mean age 32.43±8.6 y, 57.8% male) and the standard-care group (237 patients) had comparable baseline characteristics, including age, sex, and IBD type, and similar rates of hospital admissions from the ED (46.7% vs. 38.8%, P=0.32). The intervention group more frequently underwent computed tomography (40% vs. 8%, P<0.001) and surgical interventions (13.3% vs. 0.8%, P<0.001) within the same hospital admission, compared with the standard-care group. In the intervention group, 24 patients were discharged from the ED, of whom 17 patients visited the IBD clinic (median 5 d postdischarge) and the majority were referred to ambulatory IBD-MDT services (dietitian: 46.7%, psychologist: 6.7%, advanced endoscopist: 8.9%, and proctology services: 6.7%). The intervention group had significantly fewer ED revisits than the standard-care group (30 d: 4.4% vs. 19.8%, P=0.013; 90 d: 4.4% vs. 35.9%, P<0.001; 180 d: 6.7% vs. 43%, P<0.001). CONCLUSION: Proactive specialized ED assessments and IBD-MDT interventions after a hospital discharge were preferable; they significantly reduced the ED revisit rate for at least 6 months.
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Enfermedades Inflamatorias del Intestino , Alta del Paciente , Adulto , Cuidados Posteriores , Servicio de Urgencia en Hospital , Femenino , Hospitalización , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/terapia , Masculino , Adulto JovenRESUMEN
BACKGROUND: Threshold values for 13 C-urea breath test (13C-UBT) positivity may be affected by various sociodemographic, host, bacterial, and laboratory factors. Manufacturer recommended cutoffs for 13C-UBT assays may not be applicable in all settings. Optimizing 13C-UBT cutoffs may have profound public health ramifications. We aimed to determine the optimal threshold for 13C-UBT positivity in our population. METHODS: Consecutive test samples collected at our central laboratory from patients undergoing a first-time 13C-UBT between 1 January 2010 and 31 December 2015 were included. The difference between values at 30 minutes and at baseline (T30-T0) was expressed as delta over baseline (DOB). Cluster analysis was performed on the 13C-UBT test results to determine the optimal cutoff point with minimal interclass variance. RESULTS: Two lakhs thirty four thousand eight hundred thirty one patients (87 291 (37.2%) male, age 39.9 ± 19.9) underwent a first-time 13C-UBT, including 124 701 (53.1%) negative and 110 130 (46.9%) positive tests, using the manufacturer-recommended cutoff of 3.5 DOB. Cluster analysis determined an optimized cutoff of 2.74 DOB, representing an additional 2180 (0.93%) positive subjects who had been previously categorized as negative according to the manufacturer-specified cutoff of 3.5 DOB. Mean positive and negative DOB values were 19.54 ± 14.95 and 0.66 ± 0.51, respectively. The cutoffs for male and female subjects were 2.23 and 3.05 DOB, respectively. Threshold values for <45-year-olds, 45-60-year-olds and >60-year-olds were 2.67, 2.55, and 2.93 DOB, respectively. Of the 2180 (0.93%) patients with DOB 2.73-3.49, 289 (13.3%) performed a subsequent 13C-UBT and 140 (48.4%) remained positive when tested at 20.3 ± 14.4 months. CONCLUSIONS: Major referral laboratories should optimize threshold values for 13C-UBT positivity for their geographical location. Different cutoff values should be applied for male and female subjects.
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Pruebas Respiratorias/métodos , Isótopos de Carbono/análisis , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori , Urea/análisis , Adulto , Isótopos de Carbono/química , Análisis por Conglomerados , Estudios de Cohortes , Femenino , Infecciones por Helicobacter/metabolismo , Humanos , Laboratorios , Masculino , Persona de Mediana Edad , Urea/química , Adulto JovenRESUMEN
BACKGROUND/AIMS: Although the efficacy of first-line treatment for Helicobacter pylori infection should aim to be > 90%, it is unclear whether this target has been achieved in Israel. We aimed to determine the success rate of treatment for H. pylori and to describe temporal changes in our region. Methods: Adult patients who underwent a first-time -C13-urea breath test (C13-UBT) at Clalit Health Services between January 1, 2010 and December 31, 2015 were included. In order to isolate a naïve "test-and-treat" population who were unlikely to have undergone an initial endoscopy-based H. pylori test, we excluded patients ≥45 years and those with any previous C13-UBT. RESULTS: A total of 94,590 subjects (36.1% male, age 28.5 ± 6.0) who underwent at least one C13-UBT during the study period were included. C13-UBT was positive in 48,509 (51.3%) subjects. A confirmatory post-treatment C13-UBT was performed in 37.8, 44.1, 46.6, and 45.9% following 1st, 2nd, 3rd, and 4th-line treatment respectively. Eradication was successful in 65.4% following first-line treatment, and eradication success improved during the study period (59.2, 63.3, 65.7, 66.0, 69.0, and 73.1% in 2010, 2011, 2012, 2013, 2014, and 2015 respectively; OR 1.11; 95% CI 1.09-1.13; p < 0.0001). Eradication was successful in 44.7% following second-line treatment, although eradication success did not significantly improve during the study period (OR 1.05; 95% CI 0.99-1.10; p = 0.09). CONCLUSIONS: Despite the increasing success of first-line treatment for H. pylori infection over the study period, eradication rates remain suboptimal. Initiatives to implement the Toronto and Maastricht Consensus Reports should be advanced.
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Antibacterianos/uso terapéutico , Erradicación de la Enfermedad/tendencias , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/aislamiento & purificación , Adulto , Pruebas Respiratorias , Femenino , Gastroscopía , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/microbiología , Humanos , Israel/epidemiología , Masculino , Prevalencia , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Barrett's esophagus (BE) is a known complication of gastroesophageal reflux disease. In a previous study, we described a high prevalence of intestinal metaplasia (IM) in patients with an irregular Z line. However, the clinical importance of this finding is unclear. GOALS: To evaluate the long-term development of BE and relevant complications in patients diagnosed with an irregular Z line, with or without IM, on routine esophago-gastro-duodenoscopy (EGD). METHODS: In our previously described cohort, 166 out of 2000 consecutive patients were diagnosed with an incidental irregular Z line. Of those with irregular Z line, 43% had IM. In this continuation study, patients' status was reassessed after a median follow-up of 70 months. Patients were divided into two groups: Patients with IM (IM-positive group) and without IM (IM-negative group). The incidence of long-term development of BE, dysplasia, and esophageal adenocarcinoma were compared between groups. RESULTS: At least one follow-up EGD was performed in 102 (61%) patients with an irregular Z line. Endoscopic evidence of BE was found in eight IM-positive patients (8/50 [16%]) and in one IM-negative patient (1/52 [1.9%]). Two (4%) IM-positive patients developed BE with low-grade dysplasia. None of the patients developed high-grade dysplasia, or esophageal adenocarcinoma. CONCLUSIONS: Patients with irregular Z line do not develop major BE complication in more than 5 years of follow-up.
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Adenocarcinoma/patología , Esófago de Barrett/patología , Transformación Celular Neoplásica/patología , Neoplasias Esofágicas/patología , Esófago/patología , Lesiones Precancerosas/patología , Adenocarcinoma/epidemiología , Adulto , Anciano , Esófago de Barrett/epidemiología , Biopsia , Progresión de la Enfermedad , Endoscopía del Sistema Digestivo , Neoplasias Esofágicas/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Israel/epidemiología , Masculino , Metaplasia , Persona de Mediana Edad , Clasificación del Tumor , Lesiones Precancerosas/epidemiología , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
BACKGROUND: Circulating endothelial progenitor cells (EPCs) are bone marrow-derived stem cells able to migrate to sites of damaged endothelium and differentiate into endothelial cells. Altered EPC level and function have been described in various inflammatory diseases and have been shown to augment vasculogenesis in murine models. Previous studies of EPC in the context of Crohn's disease (CD) have yielded conflicting results. AIM: To determine whether the circulating levels of EPCs are changed in the context of CD. METHODS: CD patients and healthy controls were recruited. Disease activity was assessed by CDAI. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by FACS analysis using anti-CD34, anti-VEGF receptor-2, anti-CD133, and anti-CD45 markers. RESULTS: Eighty-three subjects, including 32 CD patients and 51 controls were recruited, including 19 (59.4 %) and 23 (45 %) males (p = 0.26), aged 34.8 ± 14.9 and 43.3 ± 18.5 years (p = 0.64), in cases and controls, respectively. Mean CDAI was 147 ± 97, disease duration was 12.7 ± 11.1 years, and 28 (87.5 %) were receiving biologics for a mean duration of 21.7 ± 16.8 months. The mean level of peripheral EPCs in CD patients was 0.050 ± 0.086 percent and 0.007 ± 0.013 % in controls (p < 0.01). There was no significant correlation between EPC levels and age (r = -0.13, p = 0.47), CDAI (r = -0.26, p = 0.15), disease duration (r = -0.04, p = 0.84), or duration of treatment with biologics (r = 0.004, p = 0.99). CONCLUSION: EPCs are elevated in patients with CD. Further studies are needed to examine the function of EPCs and their possible role as a marker of disease severity or therapeutic response.
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Antígenos CD/metabolismo , Productos Biológicos/uso terapéutico , Enfermedad de Crohn , Células Progenitoras Endoteliales/metabolismo , Factores de Crecimiento Endotelial Vascular/metabolismo , Adulto , Antígenos CD/análisis , Médula Ósea/metabolismo , Enfermedad de Crohn/inmunología , Enfermedad de Crohn/terapia , Femenino , Humanos , Leucocitos Mononucleares/patología , Masculino , Persona de Mediana Edad , Gravedad del Paciente , Estadística como AsuntoRESUMEN
BACKGROUND AND AIMS: Surveillance colonoscopies are crucial for high-risk patients with inflammatory bowel diseases (IBD) to detect colorectal carcinoma (CRC). However, there is no established quality metric for dysplasia detection rate (DDR) in IBD surveillance. This study assessed the DDR in a dedicated surveillance program at a tertiary referral center for IBD. METHODS: Consecutive patients with quiescent colitis were enrolled in a cross-sectional study evaluating DDR. High-definition colonoscopy with dye chromoendoscopy (DCE) was performed by a specialized operator. Advanced dysplasia (AD) was defined as low-grade dysplasia ≥ 10 mm, high-grade dysplasia, or colorectal cancer. Risk factors for dysplasia detection were analyzed. RESULTS: In total, 119 patients underwent 151 procedures, identifying 206 lesions, of which 40 dysplastic with seven AD . Per-lesion and per-procedure DDR were 19.4 % and 20.5 %, respectively. The per-procedure AD detection rate (ADDR) was 4.6 %. A Kudo pit pattern of II-V had a sensitivity of 92.5 % for dysplasia detection but a false positive rate of 64.8 % (p < 0.001). Age at diagnosis and at index colonoscopy and past or indefinite dysplasia were associated with per-procedure dysplasia detection. CONCLUSIONS: In a real-world setting, a dedicated surveillance program achieved a high DDR. We suggest that optimal DDR in high-risk IBD patients be defined and implemented as a standardized quality measure for surveillance programs.
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Neoplasias Colorrectales , Enfermedades Inflamatorias del Intestino , Humanos , Centros de Atención Terciaria , Estudios Transversales , Enfermedades Inflamatorias del Intestino/complicaciones , Colonoscopía/métodos , Hiperplasia , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/etiologíaRESUMEN
INTRODUCTION: Real-world data on tofacitinib's effectiveness is limited and mainly retrospective or registry-based. We elected to conduct a pragmatic prospective study to assess the efficacy of tofacitinib for moderate to severe ulcerative colitis (UC), aiming to evaluate the ability of intestinal ultrasound (IUS) to discriminate responders vs. non-responders in real-time. METHODS: This pragmatic prospective clinical study included consecutive adult patients starting tofacitinib treatment for active moderate to severe UC. Patients were evaluated at baseline and after 8 weeks of tofacitinib (clinical, biomarker, endoscopy, and IUS). The primary outcome was clinical response defined by a decrease in the full Mayo score (fMS) of ≥3 at week 8. Next, we explored ultrasonographic parameters in the sigmoid colon as potential real-time classifiers to differentiate between responders and non-responders at week 8. RESULTS: Overall, 30 adult patients started tofacitinib; the median age was 26.3 years (IQR 22.5-39.8), and 50% were female. Most patients (86.6%) had left-sided or extensive colitis, 96.7% had previously failed biologic therapy, and 60% (18/30) were on oral corticosteroids at the start of tofacitinib. At week 8, clinical response (a decrease in the fMS ≥ 3) and remission (fMS ≤ 2) rates were 40% (12/30) and 20% (6/30), respectively. Biomarker response (FC < 250µg/g) and biomarker normalization (FC ≤ 100µg/g) were achieved in 47.6% (10/21) and 38.1% (8/21) of patients, respectively. Endoscopic healing (endoscopic Mayo sub-score [EMS] ≤ 1) was achieved in 33.3% (10/30) of patients. Sigmoid bowel wall normalization as assessed by IUS (sBWT ≤ 3) was achieved in 18.2% (4/22). The best sBWT cut-off at week 8 to accurately classify endoscopic healing vs. no healing was a sBWT of 3.6 mm (AUC of 0.952 [95% CI: 0.868-1.036], p < 0.001). CONCLUSION: In this real-world pragmatic prospective study, tofacitinib was an effective treatment for moderate to severe UC, and IUS at week 8 accurately discriminated treatment response from non-response.
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Colitis Ulcerosa , Piperidinas , Pirimidinas , Ultrasonografía , Humanos , Piperidinas/uso terapéutico , Piperidinas/administración & dosificación , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/diagnóstico por imagen , Colitis Ulcerosa/diagnóstico , Femenino , Masculino , Pirimidinas/uso terapéutico , Estudios Prospectivos , Adulto , Resultado del Tratamiento , Adulto Joven , Índice de Severidad de la Enfermedad , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificaciónRESUMEN
OBJECTIVE: Drug sustainability (DS), a surrogate marker for drug efficacy, is important, especially when aiming for precision medicine. However, it lacks reliable prediction methods. AIMS: To develop and externally validate a web-based artificial intelligence(AI)-derived tool for predicting DS of infliximab and vedolizumab in patients with moderate-to-severe Ulcerative Colitis (UC). METHODS: Data from three Israeli centers included infliximab or vedolizumab patients treated for >54 weeks. Sustainability meant no corticosteroids, hospitalizations or surgeries. Machine learning techniques predicted >54-week and overall DS using baseline clinical data. RESULTS: The model was developed using data from 246 patients from Rabin Medical Center and externally validated on 67 patients from Rambam Health Care Campus and Sheba Medical Center. No significant difference in DS was observed across the datasets. Most patients were biologic-naïve and primarily treated with vedolizumab. The model performed well, with an area under the ROC curve of 0.86, and showed good accuracy (65.5 %-76.9 %) across the test sets. CONCLUSIONS: The study introduces a novel, AI-based tool for predicting >54-week DS of infliximab and vedolizumab in moderate-to-severe UC, using baseline parameters. This can aid clinical decision-making in the framework of precision medicine, promising to optimize disease management while maintaining physician autonomy.
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BACKGROUND AND AIM: Drug sustainability (DS) is a surrogate marker for treatment efficacy. We aimed to compare the DS of two main biologics used to treat moderate-to-severe ulcerative colitis (UC), infliximab (IFX) and vedolizumab (VDZ), in a real-world setting. METHODS: We conducted a retrospective cohort study at a tertiary medical center in Israel. We included patients treated between 1 December 2017 and 1 May 2021, who were followed for up to 300 weeks. DS was defined as corticosteroid-, surgical-, and hospitalization-free treatment. RESULTS: 217 patients with UC were included. VDZ had a significantly longer median DS of 265.6 weeks compared to IFX's 106.5 weeks (p = 0.001) in treatment-naïve patients, even when adjusting for disease severity (HR 0.55 95 CI 0.3-0.98, p = 0.042). In treatment-experienced patients, DS was comparable between IFX and VDZ (p = 0.593). CONCLUSIONS: VDZ showed significantly longer DS in treatment-naïve patients with UC compared to IFX, also when adjusted for disease severity. There was no difference in DS between VDZ and IFX in treatment-experienced patients and patients switching from one drug to another. VDZ may be a suitable first-line treatment for biologic-naïve patients with moderate-to-severe UC.
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Background: Real-world data on outcomes of patients with newly diagnosed Crohn's disease (ndCD) is limited. We aimed to assess the achievement of corticosteroid-free clinical remission (CS-free CR) and other therapeutic targets 1 year after diagnosis in a cohort of patients with ndCD treated by a multidisciplinary team (MDT). Methods: A prospective observational cohort study was conducted on consecutive treatment-naïve adults with ndCD. Patients received management at the treating physician's discretion, along with a tailored nutritional plan provided by an inflammatory bowel disease (IBD)-oriented dietitian. Patients were guided and educated by an IBD nurse, with flexible communication access to the IBD team. Therapeutic targets were assessed at 1 year. Multivariable logistic regression was used to evaluate predictors of CS-free CR. Results: Seventy-six patients (50% female) with a median age of 27 (22-39) years were eligible. Over 75% of patients were assessed by IBD-oriented dietitians and the IBD nurse. Within a median of 4.3 (2.5-6.7) months from diagnosis 60.5% initiated biologics (96% anti- tumor necrosis factor). Dietary intervention was applied to 77.6% of the cohort, either monotherapy (33.9%) or add-on (66.1%). At 1 year, 64.5% of patients achieved sustained CS-free CR, 56.6% biochemical remission, 55.8% endoscopic response, 44.2% endoscopic remission, 30.8% deep remission, and in 39.5% there was an improvement in health-related quality of life (HRQoL). Predictors for CS-free CR were uncomplicated phenotype (B1/P0), lower body mass index, and lower patient-reported outcome 2 scores at diagnosis. Conclusions: In a real-world setting at a tertiary medical center, a cohort of ndCD patients treated by an MDT resulted in favorable 1-year outcomes. Over 60% achieved CS-free CR, along with significant improvements in biomarkers and HRQoL.
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Vaccines are pivotal for control of the coronavirus disease (COVID-19) pandemic. Patients with inflammatory bowel diseases (IBDs) treated with antitumor necrosis factor (TNF)-α have lower serologic response after two COVID-19 vaccine doses. Data regarding a third vaccine dose are scarce. An Israeli multicenter prospective observational study recruited 319 subjects: 220 with IBD (79 treated with anti-TNFα) and 99 healthy control (HC) participants. All patients received two mRNA-BNT162b2 vaccines (Pfizer/BioNTech), 80% of whom received a third vaccine dose. Evaluation included disease activity, anti-spike (S) and nucleocapsid (N) antibody levels, anti-TNFα drug levels, and adverse events (AEs). All participants showed significant serologic response one month after receiving a third dose. However, three months later, the anti-S levels decreased significantly in patients treated with anti-TNFα compared with the non-anti-TNFα and HC groups. A correlation between serologic response to the third vaccine dose and anti-TNF drug levels was not found. No significant AE or IBD exacerbation was observed. Importantly, lower serologic response after the third vaccine dose predicted infection. A third dose of BNT162b2 is effective and safe in patients with IBD. Lower serologic response predicted infection, even in seropositive subjects. Lower serologic responses and their rapid decline suggest a fourth vaccine dose in this patient population.
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BACKGROUND: Autoimmune pancreatitis [AIP] is rarely associated with inflammatory bowel disease [IBD]. The long-term outcomes of AIP and IBD in patients with coexisting AIP-IBD and predictors of complicated AIP course have rarely been reported. METHODS: An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collected cases of AIP diagnosed in patients with IBD. Complicated AIP was defined as a composite of endocrine and/or exocrine pancreatic insufficiency, and/or pancreatic cancer. We explored factors associated with complicated AIP in IBD. RESULTS: We included 96 patients [53% males, 79% ulcerative colitis, 72% type 2 AIP, age at AIP diagnosis 35â ±â 16 years]. The majority of Crohn's disease [CD] cases [78%] had colonic/ileocolonic involvement. In 59%, IBD preceded AIP diagnosis, whereas 18% were diagnosed simultaneously. Advanced therapy to control IBD was used in 61% and 17% underwent IBD-related surgery. In total, 82% of patients were treated with steroids for AIP, the majority of whom [91%] responded to a single course of treatment. During a mean follow-up of 7 years, AIP complications occurred in 25/96 [26%] individuals. In a multivariate model, older age at AIP diagnosis was associated with a complicated AIP course (odds ratio [OR]â =â 1.05, pâ =â 0.008), whereas family history of IBD [ORâ =â 0.1, pâ =â 0.03], and CD diagnosis [ORâ =â 0.2, pâ =â 0.04] decreased the risk of AIP complications. No IBD- or AIP-related deaths occurred. CONCLUSIONS: In this large international cohort of patients with concomitant AIP-IBD, most patients have type 2 AIP and colonic IBD. AIP course is relatively benign and long-term outcomes are favourable, but one-quarter develop pancreatic complications. Age, familial history of IBD, and CD may predict uncomplicated AIP course.
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Enfermedades Autoinmunes , Pancreatitis Autoinmune , Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Pancreatitis , Masculino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Femenino , Pancreatitis Autoinmune/complicaciones , Pancreatitis/epidemiología , Pancreatitis/etiología , Estudios Retrospectivos , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/epidemiología , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/diagnóstico , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/terapia , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/epidemiologíaRESUMEN
Background: Advanced endoscopic technologies led to significant progress in the definition of endoscopic remission of ulcerative colitis (UC) and correlate better with histological changes, compared with standard endoscopy. However, while studies have assessed the diagnostic accuracy of endoscope technologies individually, there are currently limited data comparing between technologies. As such, the aim of this systematic review was to pool data from the existing literature and compare the correlations between endoscopy and histologic disease activity scores across endoscope technologies. Methods: We searched PubMed and Embase until February 2021 for eligible studies reporting the correlation between endoscopy and histology activity scores in UC. Studies were grouped by endoscope technology as standard-definition white light (SD-WLE), high-definition white light (HD-WLE) or electronic virtual chromoendoscopy (VCE) and comparisons made between these groups. Results: A total of N = 27 studies were identified, of which N = 12 were included in a meta-analysis of correlations between endoscopic and histological activity scores. Combining these studies identified considerable heterogeneity (I 2: 89-93%) and returned a pooled correlation coefficient (ρ) for the SD-WLE group of 0.74, which did not differ significantly from HD-WLE (ρ: 0.65, p = 0.521) or VCE (ρ: 0.70, p = 0.801). In addition, N = 4 studies reported the accuracy of endoscopic activity scores on WLE and VCE to diagnose histological remission. Pooling these found significantly higher accuracy for VCE, compared with WLE [risk ratio: 1.13, 95% confidence interval (CI): 1.07-1.19, p < 0.001]. Conclusion: Activity scores assessed using endoscopy are strongly correlated with activity on histology regardless of endoscopic technology. VCE seems to be more accurate in predicting histological remission than WLE. However, given the heterogeneity between the included studies, head-to-head trials are warranted to confirm these findings.
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Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNFα (non-anti-TNFα) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients with IBD stratified by therapy compared to HCs. Subjects enrolled in a prospective, controlled, multi-center Israeli study received two BNT162b2 doses. Anti-S levels, functional activity, specific B cells, antigen cross-reactivity, anti-nucleocapsid levels, adverse events and IBD disease score were detected longitudinally. In total, 240 subjects, 151 with IBD (94 not treated with anti-TNFα and 57 treated with anti-TNFα) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNFα had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNFα. Importantly, all seronegative subjects were patients with IBD; of those, >90% were treated with anti-TNFα. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients.
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BACKGROUND: Gastric intestinal metaplasia is a pre-cancerous condition associated with multiple factors. OBJECTIVE: We evaluated whether cumulative proton pump inhibitor dose is associated with the diagnosis of gastric intestinal metaplasia while controlling for multiple variables. METHODS: We retrospectively identified patients who underwent upper endoscopy with gastric biopsy between 2005 and 2014. Covariate data retrieved included age, sex, ethnicity, smoking status, Helicobacter pylori status (based on clarithromycin-amoxicillin-proton pump inhibitor issued), cumulative proton pump inhibitor issued within 10 years (quartiles [PPI-Q1-4 ] of daily drug dose), anti-parietal cell antibodies, body mass index and comorbidity index. RESULTS: Of the 14,147 included patients (median age 63.4 years; women 54.4%; Helicobacter pylori-positive 29.0%), 1244 (8.8%) had gastric intestinal metaplasia. Increasing age, Helicobacter pylori infection, smoking, anti-parietal cell antibodies and proton pump inhibitor use were all associated with the diagnosis of gastric intestinal metaplasia. Upper quartiles of cumulative proton pump inhibitor doses (PPI-Q4 and PPI-Q3 vs. PPI-Q1 ) were associated with the diagnosis of gastric intestinal metaplasia: adjusted odds ratios 1.32 (95% confidence interval [CI] 1.111.57) and 1.27 (95% CI 1.07-1.52), respectively, for the whole cohort (Ptotal 0.007, Ptrend 0.013), 1.69 (95% CI 1.23-2.33) and 1.40 (95% CI 1.04-1.89), respectively, for Helicobacter pylori-positive patients (Ptotal 0.004, Ptrend 0.005) and 1.21 (95% CI 0.98-1.49) and 1.20 (95% CI 0.96-1.49), respectively, for Helicobacter pylori-negative patients (Ptotal 0.288, Ptrend 0.018). Upper quartiles of proton pump inhibitor dose were associated with a 5-10-fold increased risk of low-grade dysplasia. CONCLUSIONS: Among Helicobacter pylori-positive patients, proton pump inhibitor use appears to be associated with a dose-dependent increased likelihood of gastric intestinal metaplasia.
Asunto(s)
Inhibidores de la Bomba de Protones/efectos adversos , Estómago/patología , Adulto , Anciano , Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Anticuerpos/análisis , Índice de Masa Corporal , Claritromicina/uso terapéutico , Intervalos de Confianza , Femenino , Gastroscopía , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Humanos , Masculino , Metaplasia/inducido químicamente , Metaplasia/epidemiología , Persona de Mediana Edad , Oportunidad Relativa , Células Parietales Gástricas/inmunología , Lesiones Precancerosas/inducido químicamente , Lesiones Precancerosas/epidemiología , Inhibidores de la Bomba de Protones/administración & dosificación , Estudios Retrospectivos , Fumar/efectos adversosRESUMEN
BACKGROUND AND AIMS: Skin eruptions are prevalent among patients with inflammatory bowel diseases (IBD), often associated with therapies and frequently leading to dermatological consults and treatment interruptions. We aimed to assess the impact of joint shared decision-making in a multidisciplinary (MDT) IBD-DERMA clinic. METHODS: This retrospective cohort study assessed a consecutive group of patients with IBD who were referred for consultation in an MDT clinic at a tertiary referral center in Israel. RESULTS: Over 1 year, 118 patients were evaluated in the MDT-IBD-DERMA clinic: 68 (57.6%) males; age - 35.2â±â13.5 years, disease duration - 7.1 (interquartile range: 3.7-13.9) years; Crohn's disease - 94/118 (79.6%). Skin eruption induced by an anti-tumor necrosis factor (TNF) were the most common diagnoses [46/118 (39%)], including psoriasiform dermatitis (PD) - 31/46 (67.4%) and inflammatory alopecia (IA) - 15/46 (32.6%). Of these, 18 patients (39.1%) continued the anti-TNF agent concomitantly with a topical or systemic anti-inflammatory agent to control the eruption. The remaining 28 patients (60.9%) discontinued the anti-TNF, of whom 16/28 (57.1%) switched to ustekinumab. These strategies effectively treated the majority [38/46 (82.6%)] of patients. Continuation of the anti-TNF was possible in a significantly higher proportion of patients with PD: 12/31 (38.7%) than only one in the IA group, pâ=â0.035. There was a higher switch to ustekinumab among the IA 7/15 (46.6%) compared with the PD 7/31 (22.6%) group, Pâ=â.09. Following IBD-DERMA advised intervention, IBD deteriorated in 9/4 6(19.5%) patients, 5/9 on ustekinumab (PD versus IA, Pâ=âNS). CONCLUSION: Shared decision-making in an integrated IBD-DERMA clinic allowed successful control of skin eruptions while preserving control of the underlying IBD in more than 80% of cases. Patients with IA profited from a switch to ustekinumab.
RESUMEN
BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is a rare chronic progressive cholestatic disorder. We assessed its characteristics and natural history in Israel and compared its outcome with respect to coexisting inflammatory bowel disease (IBD). METHODS: Data on characteristics, course and outcome were retrospectively retrieved on patients diagnosed with PSC from five large Israeli medical centers between 1988 and 2012. Patients with isolated PSC were compared with those with coexisting IBD to identify predictors of outcome. RESULTS: Of 141 patients (56% males) with confirmed PSC, 98 (69.5%) had coexisting IBD. The average age at presentation was 38.8 ± 15.4 years and duration of follow-up was 7.93 ± 6.26 years. The crude estimated point prevalence was 4 cases per 105 persons. Demographics and clinical characteristics were similar among all patients except for symptoms at diagnosis (which were more prevalent among PSCIBD patients) and utilization of multiple diagnostic modalities (which was more prevalent among isolated-PSC patients). More than one-third of the entire cohort had cirrhosis. A total of 15 patients (10.6%) died and 19 patients (13.5%) developed malignancy during follow-up. Nine patients (6.3%) underwent liver transplantation. Mean survival for the entire cohort was 26.3 ± 1.4 years and mean transplant-free survival was 23.5 ± 1.6 years. Cox proportional hazard regression for transplantation or death revealed two independent risk factors: cirrhosis and malignancy [hazard ratio 4.25 (p = 0.004) and 2.58 (p = 0.046), respectively]. CONCLUSIONS: Survival rate of PSC patients in Israel is longer than reported rates worldwide and is independent of coexisting IBD.