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BACKGROUND: Sedation increases colonoscopy risks and prolongs recovery time. We examined whether virtual reality (VR) can substitute for sedation. The primary outcome was the overall satisfaction of patients who underwent colonoscopy with VR headset compared with patients who underwent standard sedation. Pain during the procedure, polyp detection rate (PDR), colonoscopy duration, post-colonoscopy adverse events, post-colonoscopy recovery, time-to-return to daily functions, and turnaround time at the endoscopy unit were secondary outcomes. METHODS: The study was approved by Sheba Medical Center's ethics committee IRB number 21-8177-SMC. Sixty patients were sequentially enrolled in a 1:1 ratio to either standard sedated colonoscopy or VR-unsedated procedure, and all patients signed a written informed consent. 28/30 patients successfully completed the colonoscopy using VR headset. Overall satisfaction score was comparable between the groups. RESULTS: There was no difference between VR and controls in colonoscopy duration, or PDR. VR patients had numerically lower rate of post-colonoscopy adverse events than controls. The proportion of VR patients who reported resuming daily activities on the day of the procedure was significantly higher than in the control group. The VR group patients spent significantly less time in the hospital compared to the control group. CONCLUSIONS: VR technology can provide adequate substitution for sedation for most patients undergoing colonoscopy and offers comparable patient satisfaction and faster return to daily activities.
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Colonoscopía , Sedación Consciente , Satisfacción del Paciente , Realidad Virtual , Humanos , Colonoscopía/métodos , Femenino , Masculino , Proyectos Piloto , Persona de Mediana Edad , Sedación Consciente/métodos , Anciano , Adulto , Dolor Asociado a Procedimientos Médicos/prevención & control , Dolor Asociado a Procedimientos Médicos/etiologíaRESUMEN
INTRODUCTION: Patency capsule (PC) is a recommended procedure to rule out small bowel stenosis before video capsule endoscopy (VCE). We examined future clinical outcomes among patients with a failed PC vs patients in whom the PC had passed (passed PC). METHODS: A post hoc analysis of 2 prospective cohort studies of adult patients with quiescent small bowel Crohn's disease (CD) who underwent PC between 2013 and 2020. The primary composite outcome was the need for intestinal surgery or endoscopic dilation during follow-up in patients with or without a failed PC. RESULTS: A total of 190 patients were included (47: failed PC and 143: passed PC, median follow-up 34.12 months). Patients with a failed PC had higher rates of the primary composite outcome (21.3% vs 1.4%, hazard ratio [HR] 20.3, 95% confidence interval [CI] 4.4-93.7, P < 0.001) and also secondary outcomes including intestinal surgery (14.9% vs 0.70%, P < 0.001), endoscopic dilation (14.9% vs 0.70%, P < 0.001), admissions (23.3% vs 5.7%, P < 0.001), and clinical flares (43.9% vs 27.7%, P = 0.005) during follow-up compared with controls. Failed PC was the only statistically significant factor for surgery and/or endoscopic dilation, regardless of a B2/B3 phenotype at baseline. In sensitivity analyses restricted only to patients with a stricturing phenotype (n = 73), a failed PC still predicted the long-term composite outcome (HR 8.68, 95% CI 1.72-43.68, P = 0.002). Of the 190 patients ingesting a PC, only 1 patient with a failed PC had 48 hours of self-limiting mild symptoms. DISCUSSION: Patients with clinically stable CD with a failed PC have worse long-term clinical outcomes than those without, independently of the CD phenotype. Standalone PC may serve as a novel, safe, and affordable prognostic examination to identify patients with quiescent CD who have a higher risk for future worse clinical outcomes.
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Endoscopía Capsular , Enfermedad de Crohn , Obstrucción Intestinal , Humanos , Enfermedad de Crohn/diagnóstico , Estudios Prospectivos , Obstrucción Intestinal/etiología , Obstrucción Intestinal/diagnóstico , Constricción PatológicaRESUMEN
BACKGROUND AND AIMS: The expression of tissue and serum matrix metalloproteinase-7 (MMP-7) was shown to be elevated both in colon cancer and dysplastic lesions. We aimed to evaluate, for the first time, its role as a diagnostic marker in Lynch syndrome (LS) carriers, a hereditary syndrome with predisposition to colon cancer. METHODS: This was a case control study. Baseline serum MMP-7 levels were determined by ELISA in 40 colon cancer patients, 62 LS-carriers and 60 healthy controls. Retrieved data from medical files included demographics, background diseases, clinical data regarding tumor characteristics and genetic data. We assessed the association of serum MMP-7 levels with different variables in the study cohort using linear regression model adjusted for potential confounders. RESULTS: In crude analysis, serum MMP-7 levels were significantly higher in colon cancer group compared to LS-carriers and controls [median (IQR) 4.1 ng/ml (2.7-6.0), 2.3 ng/ml (1.7-3.1), 2.5 ng/ml (1.5-3.7), respectively; p value - p < 0.001) while there was no difference between the two last groups (p value = 0.583). However, after adjusting for age and gender, LS-carriers' patients had 18% higher concentrations of serum MMP-7 compared to healthy controls (p value = 0.037), while colon cancer patients had 50% higher serum MMP-7 level in comparison to healthy controls (p value < 0.001). Additionally, age was positively associated with higher serum MMP-7 levels across all study groups (r = 0.67, p value < 0.001). In contrast, no correlation was observed between serum MMP-7 and either tumor staging and gene mutation. CONCLUSIONS: Age-adjusted serum MMP-7 levels in asymptomatic LS carriers are higher than its levels in healthy population. While in colon cancer, MMP-7 higher level probably reflects the tumor burden and may have a prognostic effect, its significance and clinical applicability as a biomarker for tumorigenesis in LS is less clear and should be elucidated.
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Neoplasias del Colon , Neoplasias Colorrectales Hereditarias sin Poliposis , Humanos , Metaloproteinasa 7 de la Matriz/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Estudios de Casos y Controles , BiomarcadoresRESUMEN
BACKGROUND: Jejunal disease is associated with worse prognosis in Crohn's disease. The added value of diffusion weighted imaging for evaluating jejunal inflammation related to Crohn's Disease is scarce. OBJECTIVES: To compare diffusion weighted imaging, video capsule endoscopy, and inflammatory biomarkers in the assessment of Crohn's disease involving the jejunum. METHODS: Crohn's disease patients in clinical remission were prospectively recruited and underwent magnetic resonance (MR)-enterography and video capsule endoscopy. C-reactive protein and fecal-calprotectin levels were obtained. MR-enterography images were evaluated for restricted diffusion, and apparent diffusion coefficient values were measured. The video capsule endoscopy-based Lewis score was calculated. Associations between diffusion weighted imaging, apparent diffusion coefficient, Lewis score, and inflammatory biomarkers were evaluated. RESULTS: The study included 51 patients, and 27/51 (52.9%) with video capsule endoscopies showed jejunal mucosal inflammation. Sensitivity and specificity of restricted diffusion for video capsule endoscopy mucosal inflammation were 59.3% and 37.5% for the first reader, and 66.7% and 37.5% for the second reader, respectively. Diffusion weighted imaging was not statistically associated with jejunal video capsule endoscopy inflammation (P = 0.813). CONCLUSIONS: Diffusion weighted imaging was not an effective test for evaluation of jejunal inflammation as seen by video capsule endoscopy in patients with quiescent Crohn's disease.
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Endoscopía Capsular , Enfermedad de Crohn , Humanos , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/diagnóstico por imagen , Endoscopía Capsular/métodos , Yeyuno/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Inflamación/diagnóstico , Imagen por Resonancia Magnética , Biomarcadores/análisisRESUMEN
BACKGROUND: Up to 60% of inflammatory bowel disease (IBD) patients treated with infliximab develop antibodies to infliximab (ATI), which are associated with low drug levels and loss of response (LOR). Hence, mapping out predictors of immunogenicity toward infliximab is essential for tailoring patient-specific therapy. Jewish Sephardi ethnicity, in addition to monotherapy, has been previously identified as a potential risk factor for ATI formation and infliximab failure. OBJECTIVES: To explore the association between Jewish sub-group ethnicity among patients with IBD and the risk of infliximab immunogenicity and therapy failure. To confirm findings of a previous cohort that addressed the same question. METHODS: This retrospective cohort study included all infliximab-treated patients of Jewish ethnicity with regular prospective measurements of infliximab trough levels and ATI. Drug and ATI levels were prospectively measured, clinical data was retrieved from medical charts. RESULTS: The study comprised 109 Jewish patients (54 Ashkenazi, 55 Sephardi) treated with infliximab. There was no statistically significant difference in proportion of ATI between Sephardi and Ashkenazi patients with IBD (32% Ashkenazi and 33% Sephardi patients developed ATI, odds ratio [OR] 0.944, P = 0.9). Of all variables explored, monotherapy and older age were the only factors associated with ATI formation (OR 0.336, 95% confidence interval 0.145-0.778, P = 0.01, median 34 vs. 28, interquartile range 28-48, 23-35 years, P = 0.02, respectively). CONCLUSIONS: Contrary to previous findings, Sephardi Jewish ethnicity was not identified as a risk factor for ATI formation compared with Ashkenazi Jewish ethnicity. Other risk factors remained unchanged.
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Etnicidad , Fármacos Gastrointestinales/administración & dosificación , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab/administración & dosificación , Judíos , Adulto , Estudios de Cohortes , Femenino , Fármacos Gastrointestinales/inmunología , Fármacos Gastrointestinales/farmacocinética , Humanos , Enfermedades Inflamatorias del Intestino/etnología , Enfermedades Inflamatorias del Intestino/inmunología , Infliximab/inmunología , Infliximab/farmacocinética , Masculino , Estudios Prospectivos , Estudios Retrospectivos , Insuficiencia del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: Crohn's disease (CD) is a chronic relapsing-remitting gut inflammatory disorder with a heterogeneous unpredictable course. Dysbiosis occurs in CD; however, whether microbial dynamics in quiescent CD are instrumental in increasing the risk of a subsequent flare remains undefined. METHODS: We analyzed the long-term dynamics of microbial composition in a prospective observational cohort of patients with quiescent CD (45 cases, 217 samples) over 2 years or until clinical flare occurred, aiming to identify whether changes in the microbiome precede and predict clinical relapse. Machine learning was used to prioritize microbial and clinical factors that discriminate between relapsers and nonrelapsers in the quiescent phase. RESULTS: Patients with CD in clinical, biomarker, and mucosal remission showed significantly reduced microbial richness and increased dysbiosis index compared with healthy controls. Of the 45 patients with quiescent CD, 12 (27%) flared during follow-up. Samples in quiescent patients preceding flare showed significantly reduced abundance of Christensenellaceae and S24.7, and increased abundance of Gemellaceae compared with those in remission throughout. A composite flare index was associated with a subsequent flare. Notably, higher individualized microbial instability in the quiescent phase was associated with a higher risk of a subsequent flare (hazard ratio 11.32, 95% confidence interval 3-42, P = 0.0035) using two preflare samples. Importantly, machine learning prioritized the flare index and the intrapersonal instability over clinical factors to best discriminate between relapsers and nonrelapsers. DISCUSSION: Individualized microbial variations in quiescent CD significantly increase the risk of future exacerbation and may provide a model to guide personalized preemptive therapy intensification.
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Enfermedad de Crohn/microbiología , Enfermedad de Crohn/patología , Progresión de la Enfermedad , Disbiosis/complicaciones , Microbioma Gastrointestinal/fisiología , Monitoreo Fisiológico/métodos , Adulto , Estudios de Casos y Controles , Enfermedad de Crohn/terapia , Femenino , Estudios de Seguimiento , Humanos , Mucosa Intestinal/microbiología , Modelos Lineales , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Recurrencia , Valores de Referencia , Medición de Riesgo , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
OBJECTIVES: Adalimumab is usually self-injected at home, making prospective serial-sampling studies challenging and scarce. This has led to a gap in knowledge about evolution of anti-adalimumab antibodies (AAAs) over time and its correlation with clinical and inflammatory outcomes. METHODS: A program for home visits by physicians at induction, every 3 months and at event of relapse, was established prospectively for Crohn's disease (CD) patients. At each visit, patients' clinical scores were determined and sera were obtained for C-reactive protein, drug, and AAA levels. This cohort was compared to a parallel prospective cohort of infliximab-treated CD patients. In a subgroup of 29 patients, trough and in-between-trough levels were compared, to elucidate the importance of timing of sampling during the injection cycle. RESULTS: Ninety-eight CD patients starting adalimumab were prospectively followed (median follow-up 44 weeks) and 621 serum samples were analyzed. Thirty-three patients (32%) developed AAA; 18/33 (55%) of them as early as week 2, and 26/33 (79%) by week 14. Induction period AAAs were strongly associated with primary non-response (odds ratio (OR) = 5.4, 95% confidence interval (CI): 1.6-17.8, p = 0.005). As compared to antibodies-to-infliximab (ATI), AAA formation rate over time was significantly lower (p = 0.01) and AAA were much more specific-85% of AAA events were associated with loss-of-response compared with 58% rate for ATI (p = 0.01). In 29 patients sampled serially during an injection cycle, levels of drug and AAA seemed comparable between four time-points during a single cycle both in patients with or without AAA (n = 8, n = 21, respectively). CONCLUSIONS: When followed prospectively and serially, AAAs are found to arise earlier than previously appreciated and their impact may be more pronounced for primary rather than secondary, non-response. Drug and AAA levels were similar both at trough and in-between injections, enabling to simplify therapeutic drug monitoring of adalimumab.
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Adalimumab/inmunología , Antiinflamatorios/inmunología , Enfermedad de Crohn/tratamiento farmacológico , Monitoreo de Drogas/estadística & datos numéricos , Adalimumab/administración & dosificación , Adalimumab/sangre , Adulto , Antiinflamatorios/administración & dosificación , Antiinflamatorios/sangre , Proteína C-Reactiva/análisis , Enfermedad de Crohn/sangre , Enfermedad de Crohn/inmunología , Femenino , Estudios de Seguimiento , Humanos , Infliximab/administración & dosificación , Infliximab/sangre , Infliximab/inmunología , Masculino , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVES: Evaluate the ability of MR diffusion-weighted imaging (DWI) to predict patency capsule retention in Crohn's disease (CD). METHODS: Clinical and imaging data were prospectively reviewed for 80 CD patients following patency capsule administration and MR-DWI under institutional review board (IRB) approval with informed consent. Two radiologists separately assessed the presence/absence of restricted diffusion in the distal ileum. Apparent diffusion coefficients (ADC) from three regions of interest on the ileal wall were averaged. The association between restricted diffusion and retention, and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Ability of ADC to predict retention was assessed with receiver operating characteristic (ROC) curve analysis. RESULTS: Restricted diffusion in the distal ileum was associated with capsule retention (p = 0.001, p < 0.0001). Sensitivity, specificity, PPV and NPV of restricted diffusion for capsule retention were 100.0%, 46.2%, 30.0%, 100% and 100.0%, 56.9%, 34.9%, 100%, respectively, for two radiologists. Accuracy of ADC to predict retention was high (area under the curve = 0.851, p < 0.0001). An ADC of 1.47 mm2/s showed 90.0% sensitivity and 50.0% specificity for retention. CONCLUSIONS: Sensitivity and NPV of restricted diffusion for patency capsule retention were 100%, suggesting that DWI may predict gastrointestinal tract capability to pass video camera endoscopy. KEY POINTS: ⢠Capsule endoscopy enables assessment of the gastrointestinal mucosa in Crohn's disease ⢠Prior patency capsule administration is recommended to evaluate gastrointestinal tract patency ⢠MR diffusion-weighted imaging may detect pathological constriction of the ileum ⢠Restricted diffusion in the distal ileum was associated with capsule retention ⢠MR-DWI may predict gastrointestinal tract capability to pass capsule endoscopy.
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Endoscopía Capsular/métodos , Enfermedad de Crohn/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Adulto , Anciano , Constricción Patológica/patología , Enfermedad de Crohn/patología , Femenino , Humanos , Íleon/patología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: Helicobacter pylori (HP) infection is present in about 50% of the global population, and is associated with chronic gastritis, peptic disease and gastric malignancies. HP prevalence in Crohn's disease (CD) patients was shown to be low compared to the general population, and its influence on disease activity is yet to be determined. Our aims were to determine the prevalence of HP in a selected group of CD patients with quiescent disease, and to assess the influence of its eradication on disease activity and endoscopic and laboratory activity measures. METHODS: Consecutive CD patients with quiescent disease underwent meticulous disease evaluation with MR enterography (MRE), video capsule endoscopy (VCE), CRP, fecal calprotectin and CDAI. All patients were tested for the presence of HP using stool antigen detection kit. Patients infected with HP were offered eradication treatment with sequential therapy. HP eradication was confirmed using urease breath test and stool antigen test. The influence of HP eradication on disease activity was assessed. RESULTS: Out of 56 patients enrolled, six patients (10.7%) had HP infection. Of them, five patients had gastro- duodenitis per VCE. All HP positive patients were offered eradication treatment and underwent successful eradication. Notably, 23 (50%) of patients had proximal disease per VCE, most of them (78%) were HP negative. CDAI, CRP, fecal calprotectin and VCE Lewis inflammatory score did not change significantly following HP eradication, Gastric findings on VCE were not impacted by HP eradication. CONCLUSIONS: The prevalence of HP infection in patients with quiescent CD is relatively low. Eradication of the bacteria did not significantly change neither disease activity measures nor the presence of gastro- duodenitis per VCE, suggesting it might be part of proximal CD. The influence of HP on CD activity merits further investigation.
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Enfermedad de Crohn/microbiología , Infecciones por Helicobacter/epidemiología , Helicobacter pylori , Adulto , Antibacterianos/uso terapéutico , Proteína C-Reactiva/análisis , Endoscopía Capsular , Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/patología , Erradicación de la Enfermedad , Heces/química , Heces/microbiología , Femenino , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Complejo de Antígeno L1 de Leucocito/análisis , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Prevalencia , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND AND AIMS: Evaluation of small-bowel patency is recommended before swallowing video capsule endoscopy to prevent capsule retention. This study aimed to evaluate the ability of magnetic resonance enterography (MRE) to predict patency capsule (PC) retention in patients with Crohn's disease and to identify the most predictive imaging features for retention. METHODS: Fifty-seven patients prospectively underwent MRE and PC. Two radiologists predicted PC retention. Interrater reliability was determined by using Cohen's κ coefficient. The sensitivity, specificity, and positive and negative predictive values were calculated for the predictions. Evaluation of the imaging features was done using the t test and receiver-operating characteristics; t-tests were also performed on the clinical parameters. RESULTS: The κ value for interrater reliability was 0.58. The sensitivity, specificity, PPV, and NPV for the predictions by the 2 radiologists were 92.3%, 59%, 40%, 96.3%, and 100%, 52.3%, 38.2%, 100%, respectively. The maximal stricture length (9.7 ± 3.66 cm vs 7.0 ± 3.08 cm, P = .04) and the number of prestenotic dilations (1.9 ± 1.07 vs 1.0 ± 1.38, P = .03) were associated with PC retention. The area under the receiver-operating characteristic curves was 0.69 for the maximal stricture length and 0.751 for the number of prestenotic dilations. The phenotype of the disease was the only clinical parameter significantly correlated with PC retention. CONCLUSIONS: MRE has a high NPV and sensitivity for PC retention. When capsule retention is suggested by MRE, PC should be performed before the video capsule endoscopy examination. The maximal stricture length and the number of prestenotic dilations were found to be the most predictive imaging features for PC retention.
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Enfermedad de Crohn/diagnóstico , Enfermedades Intestinales/diagnóstico , Intestino Delgado/patología , Adulto , Endoscopios en Cápsulas , Endoscopía Capsular , Constricción Patológica/diagnóstico , Constricción Patológica/patología , Femenino , Humanos , Enfermedades Intestinales/patología , Imagen por Resonancia Magnética , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
OBJECTIVES: Mucosal healing (MH) and deep remission (DR) are associated with improved outcomes in Crohn's disease (CD). However, most of the current data pertain to colonic MH and DR, whereas the evidence regarding the prevalence and impact of small bowel (SB) MH is scarce. The aim of this study was to to evaluate the prevalence of SBMH and DR in quiescent SBCD. METHODS: Patients with known SBCD in clinical remission (CDAI<150) or with mild symptoms (CDAI<220) were prospectively recruited and underwent video capsule endoscopy after verification of SB patency. Inflammation was quantified using the Lewis score (LS). SBMH was defined as LS<135, whereas a significant inflammation was defined as LS>790. Clinico-biomarker remission was defined as a combination of clinical remission and normal biomarkers. DR was defined as a combination of clinico-biomarker remission and MH. RESULTS: Fifty-six patients with proven SB patency were enrolled; 52 (92.9%) patients were in clinical remission and 21 (40.4%) in clinico-biomarker remission. SBMH was demonstrated in 8/52 (15.4%) of patients in clinical remission. Moderate-to-severe SB inflammation was demonstrated in 11/52 (21.1%) of patients in clinical remission and in 1/21 (4.7%) of patients in clinical and biomarker remission. Only 7/52 (13.5%) patients were in DR. CONCLUSIONS: SB inflammation is detected in the majority of CD patients in clinical and biomarker remission. SBMH and DR were rare and were independent of treatment modality. Our findings represent the true inflammatory burden in quiescent patients with SBCD.
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Biomarcadores/análisis , Endoscopía Capsular/métodos , Enfermedad de Crohn/diagnóstico , Diagnóstico por Imagen , Mucosa Intestinal/patología , Intestino Delgado/patología , Adulto , Enfermedad de Crohn/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Mucosa Intestinal/metabolismo , Imagen por Resonancia Magnética/métodos , Masculino , Estudios Prospectivos , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
BACKGROUND: Syndecan-1 plays a central role in maintaining normal intestinal barrier function. Shedding of syndecan-1, reflected by soluble syndecan-1 serum concentrations, is highly regulated by inflammation. AIM: To determine soluble syndecan-1 levels in inflammatory bowel disease patients and its relationship with other inflammatory markers, disease activity, and medical treatment. METHODS: Cross-sectional, pilot study in which serum concentrations of soluble syndecan-1 were analyzed by ELISA in a cohort of 41 inflammatory bowel disease patients (22 Crohn's disease, 19 ulcerative colitis) and 16 healthy controls. Disease activity was estimated by the Crohn's disease activity index, partial Mayo score, and C-reactive protein. RESULTS: Soluble syndecan-1 levels were significantly higher in inflammatory bowel disease patients compared to healthy controls (29.5 ± 13.4 vs. 21.1 ± 10.4 ng/ml, respectively, P = 0.03). Soluble syndecan-1 displayed a reliable ability to discriminate inflammatory bowel disease patients from healthy controls with a sensitivity of 95 %, specificity of 50 %, and positive predictive value of 83 %. Patients treated with anti-inflammatory medications demonstrated significantly lower soluble syndecan-1 levels compared to untreated patients (26.45 ± 9.75 vs. 38 ± 18.43 ng/ml, respectively, P = 0.008). CONCLUSIONS: Our results suggest that soluble syndecan-1 is potentially a novel diagnostic marker in the management of inflammatory bowel disease patients. Its applicability as a surrogate, prognostic biomarker remains to be determined.
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Enfermedades Inflamatorias del Intestino/sangre , Sindecano-1/sangre , Adulto , Estudios Transversales , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Proyectos Piloto , SolubilidadRESUMEN
BACKGROUND AND AIMS: Fecal calprotectin (FC) is known to be a sensitive biomarker of colonic inflammation but to a lesser degree of small bowel (SB) inflammation. Moreover, data on FC's diagnostic levels in different SB segments are scarce. We aimed to examine FC's diagnostic levels along the SB-axis in CD. METHODS: This was a post-hoc aggregated analysis of five prospective studies of adult CD patients, who underwent FC testing and SB video capsule endoscopy (VCE). Lewis score (LS) inflammation in different SB segments was tested for correlation with FC level after exclusion of colonic disease. The diagnostic levels of FC for SB inflammatory topographical-gradient were assessed using a receiver operating characteristic. RESULTS: 214 patients were included (age:30 [24-43] year-old, males-57%). For a similar SB inflammatory-activity (LS≥135), FC levels incrementally increased from proximal to distal SB segments (63 [30-121] versus 190 [78-549], p=0.005) and from distal SB segment to the colon (190 [78-549] versus 542 [185-1000], p=0.010). The best FC cutoffs to identify isolated mild proximal/distal SB-inflammation (LS≥135) were 77µgg and 123µgg, respectively. A cutoff of 234µgg was best to detect more significant proximal inflammation (LS≥350) when only mild distal SB-inflammation was present. In sensitivity analyses, this proximal-to-distal FC gradient was maintained when LS≥350 and LS≥790 were used as the inflammatory reference-values. Unlike FC, the magnitude of CRP elevation was unrelated to the topography of inflammation along the SB-axis. CONCLUSIONS: FC may serve as a topographical biomarker of CD-activity, with its sensitivity to identify mucosal inflammation increases from proximal to distal SB segments.
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BACKGROUND AND AIMS: Home self-injection of the human anti-tumour necrosis alpha [anti-TNFα] monoclonal adalimumab complicates prospective serial-sampling studies. Although a recent study examined adalimumab levels and immunogenicity in Crohn's disease [CD] patients, prospective real-world data from ulcerative colitis [UC] patients are lacking. METHODS: A three-monthly home-visit programme from induction was established prospectively for UC patients. Clinical scores were determined at each visit, and sera were obtained for assessment of drug and anti-adalimumab antibody levels. Calprotectin was measured using a smartphone-based app. This cohort was compared to a parallel prospective cohort of adalimumab-treated CD patients [POETIC1]. RESULTS: Fifty UC patients starting adalimumab [median follow-up 28 weeks] were compared to 98 adalimumab-treated CD patients [median follow-up 44 weeks]. Only 11/50 UC patients [22%] continued treatment to the end of the follow-up compared with 50/98 [51%] CD patients (odds ratio [OR]â =â 0.27, pâ =â 0.001). Loss of response was significantly more common in UC patients [ORâ =â 3.2, pâ =â 0.001]. Seventeen patients [34%] in the UC cohort developed anti-adalimumab antibodies, 9/17 [52.9%] as early as week 2. There was no difference between patient cohorts in the overall development of anti-adalimumab antibodies [34% vs 30.6%, respectively, ORâ =â 1.67, pâ =â 0.67], nor was there a difference in early immunogenicity [ORâ =â 1.39, pâ =â 0.35]. There was no difference in low drug levels [<3 µg/mL] between the two cohorts [ORâ =â 0.87, pâ =â 0.83]. CONCLUSIONS: Loss of response to adalimumab therapy was significantly more common in the UC compared to the CD cohort and was driven by a higher rate of non-immunogenic, pharmacodynamic parameters.
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Colitis Ulcerosa , Enfermedad de Crohn , Humanos , Adalimumab/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Estudios Prospectivos , Enfermedad de Crohn/tratamiento farmacológico , Factor de Necrosis Tumoral alfaRESUMEN
Background: Video capsule endoscopy (VCE) has been proven to accurately diagnose small-bowel inflammation and predict flares among patients with quiescent Crohn's disease (CD). However, data regarding its predictive role in this population over an extended follow-up are scarce. Objectives: To predict clinical exacerbation and to assess the yield of Lewis score in identifying CD patients with future clinical exacerbation during an extended follow-up (>24 months). Design: A post hoc analysis study. Methods: Adult patients with quiescent small-bowel CD who were followed with VCE, inflammatory biomarkers and magnetic resonance enterography in a prospective study (between 2013 and 2018). We extracted extended clinical data (up to April 2022). The primary composite outcome (i.e. clinical exacerbation) was defined as intestinal surgery, endoscopic dilation, CD-related admission, corticosteroid administration, or biological/immunomodulator treatment change during follow-up. Results: Of the 61 patients in the study [median age 29 (24-37) years, male 57.4%, biologic treatment 46.7%], 18 patients met the primary outcome during an extended follow-up [median 58.0 (34.5-93.0) months]. On univariable analysis, complicated [hazard ratio (HR) 7.348, p = 0.002] and stricturing disease phenotype (HR 5.305, p = 0.001) were associated with higher risk for clinical exacerbation during follow-up. A baseline VCE middle small-bowel segment Lewis score (midLS) ⩾ 135 identified patients with future exacerbation [AUC (area under the curve) 0.767, 95% confidence interval (CI) 0.633-0.902, p = 0.001, HR 6.317, 93% negative predictive value], whereas the AUC of the conventional Lewis score was 0.734 (95% CI: 0.589-0.879, p = 0.004). Sensitivity analysis restricted to patients with either complicated (n = 34) or stricturing (n = 26) disease phenotype revealed that midLS still predicted clinical exacerbation during follow-up (AUC 0.747/0.753, respectively), in these patients. Conclusion: MidLS predicts treatment failure in quiescent CD patients (median follow-up of 5 years) independently of disease phenotype.
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Background: Screening with colonoscopy for all average-risk population is probably not cost-effective due to the limited sources and over-generalization of the risk, and risk stratification can be used to optimize colorectal cancer screening. Objectives: We aimed to assess risk factors for advanced neoplasia (AN) and a classification tree algorithm to predict the risk. Design: This is a retrospective cross-sectional study. Methods: This study was composed of consecutive asymptomatic average-risk individuals undergoing first screening colonoscopy between 2008 and 2019. Detailed characteristics including background diseases, habits, and medications were collected. We used multivariable logistic regression to investigate the associations between clinical variables and the presence of AN and built a classification algorithm to predict AN. Results: A total of 3856 patients were included (73.2% male, median age 55). Adenoma and AN detection rate were 15.8% and 3.4%, respectively. On multivariable analysis, predictors of AN [odds ratio (OR), 95% confidence interval (CI)] were age (1.04, 1.01-1.06, p = 0.003), male sex (2.69, 1.56-4.64, p < 0.001), and smoking (1.97, 1.38-2.81, p < 0.001). A classification tree algorithm showed that smoking was the most important risk factor for prediction of AN (4.9% versus 2.4%, p < 0.001), followed by age with a cutoff value of 60 in the smokers (8.4% versus 3.8%, p = 0.001) and 50 in the non-smokers (2.9% versus 0.9%, p = 0.004). Conclusion: Smoking habits, old age, and male gender are highly associated with an increased risk for AN and should be incorporated in the individualized risk-assessment to adapt a screening program.
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INTRODUCTION: Syndecan-1 (SDC1) has multiple functions in tumorigenesis in general and specifically in pancreatic cancer. We aimed to evaluate SDC1 as a diagnostic and prognostic biomarker in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: In this case-control study, patients newly diagnosed with a biopsy-proven PDAC were enrolled alongside healthy individuals in a derivation-validation cohort design. Serum SDC1 was measured by enzyme-linked immunoassay. The diagnostic accuracy of SDC1 levels for diagnosing PDAC was computed. A unified cohort enriched with additional early-stage patients with PDAC was used to evaluate the association of SDC1 with survival outcomes and patient characteristics. RESULTS: In the derivation cohort, serum SDC1 levels were significantly higher in patients with PDAC (n = 39) compared with healthy controls (n = 20) (40.1 ng/mL, interquartile range 29.8-95.3 vs 25.6 ng/mL, interquartile range 17.1-29.8, respectively; P < 0.001). The receiver operating characteristic analysis area under the curve was 0.847 (95% confidence interval 0.747-0.947, P < 0.001). These results were replicated in a separate age-matched validation cohort (n = 38 PDAC, n = 38 controls; area under the curve 0.844, 95% confidence interval 0.757-0.932, P < 0.001). In the combined-enriched PDAC cohort (n = 110), using a cutoff of 35 ng/mL, the median overall 5-year survival between patients below and above this cutoff was not significantly different, although a trend for better survival after 1 year was found in the lower level group (P = 0.06). There were 12 of the 110 patients with PDAC (11%) who had normal CA 19-9 in the presence of elevated SDC1. DISCUSSION: These findings suggest serum SDC1 as a promising novel biomarker for early blood-based diagnosis of pancreatic cancer.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Sindecano-1/sangre , Biomarcadores de Tumor , Carcinoma Ductal Pancreático/patología , Estudios de Casos y Controles , Humanos , Neoplasias Pancreáticas/patología , Neoplasias PancreáticasRESUMEN
Syndecan-1, the most abundant heparan sulfate proteoglycan in the gastrointestinal tract, is reduced in the regenerative epithelium in inflammatory bowel disease (IBD). This study explored the effects of the immunomodulator glatiramer acetate (GA; Copaxone) treatment on syndecan-1 expression in dextran sodium sulfate (DSS)-induced colitis. Acute and chronic colitis was induced in C57BL/6 mice by 2 and 1.5% DSS in tap water, respectively. GA was applied subcutaneously, 2 mg per mouse per day, starting on the day of DSS induction until the mice were sacrificed. Syndecan-1 expression was assessed by immunohistochemistry. The effect of adoptive transfer of GA-specific T cells as an organ-specific therapy also was evaluated. Syndecan-1 expression was significantly lower in both colitis groups compared with that in naive mice (p < 0.0001). GA attenuated clinical scores and pathological manifestations of colitis and led to the reinstatement of normal levels of syndecan-1. After adoptive transfer, GA-specific cells homed to the surface epithelium of the distal colon, accompanied by the augmentation of syndecan-1 staining in their vicinity. We concluded that syndecan-1 expression is reduced in DSS-induced colitis and could be a potential prognostic factor in IBD. Treatment with GA exerts not only an anti-inflammatory effect but also a possible beneficial effect in stabilizing the intestinal epithelium barrier and tissue repair in DSS colitis. GA may be applied as a novel drug for IBD, shifting treatment from immunosuppression toward immunomodulation.
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Colitis/tratamiento farmacológico , Sulfato de Dextran , Péptidos/uso terapéutico , Sindecano-1/biosíntesis , Enfermedad Aguda , Traslado Adoptivo , Animales , Antiinflamatorios/farmacología , Ciego/patología , Enfermedad Crónica , Colitis/inducido químicamente , Colitis/patología , Colon/patología , Femenino , Acetato de Glatiramer , Inmunohistoquímica , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Ratones , Ratones Endogámicos C57BL , Ratones TransgénicosRESUMEN
BACKGROUND: The marijuana plant cannabis is known to have therapeutic effects, including improvement of inflammatory processes. However, no report of patients using cannabis for Crohn's disease (CD) was ever published. OBJECTIVES: To describe the effects of cannabis use in patients suffering from CD. METHODS: In this retrospective observational study we examined disease activity, use of medication, need for surgery, and hospitalization before and after cannabis use in 30 patients (26 males) with CD. Disease activity was assessed by the Harvey Bradshaw index for Crohn's disease. RESULTS: Of the 30 patients 21 improved significantly after treatment with cannabis. The average Harvey Bradshaw index improved from 14 +/- 6.7 to 7 +/- 4.7 (P < 0.001). The need for other medication was significantly reduced. Fifteen of the patients had 19 surgeries during an average period of 9 years before cannabis use, but only 2 required surgery during an average period of 3 years of cannabis use. CONCLUSIONS: This is the first report of cannabis use in Crohn's disease in humans. The results indicate that cannabis may have a positive effect on disease activity, as reflected by reduction in disease activity index and in the need for other drugs and surgery. Prospective placebo-controlled studies are warranted to fully evaluate the efficacy and side effects of cannabis in CD.