RESUMEN
Crohn's disease (CD) and ulcerative colitis (UC), two major subtypes of inflammatory bowel disease, show substantial differences in their clinical course and treatment response. To identify the genetic factors underlying the distinct characteristics of these two diseases, we performed a genome-wide association study (GWAS) between CD (n = 2359) and UC (n = 2175) in a Korean population, followed by replication in an independent sample of 772 CD and 619 UC cases. Two novel loci were identified with divergent effects on CD and UC: rs9842650 in CD200 and rs885026 in NCOR2. In addition, the seven established susceptibility loci [major histocompatibility complex (MHC), TNFSF15, OTUD3, USP12, IL23R, FCHSD2 and RIPK2] reached genome-wide significance. Of the nine loci, six (MHC, TNFSF15, OTUD3, USP12, IL23R and CD200) were replicated in the case-case GWAS of European populations. The proportion of variance explained in CD-UC status by polygenic risk score analysis was up to 22.6%. The area under the receiver-operating characteristic curve value was 0.74, suggesting acceptable discrimination between CD and UC. This CD-UC GWAS provides new insights into genetic differences between the two diseases with similar symptoms and might be useful in improving their diagnosis and treatment.
Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Humanos , Colitis Ulcerosa/genética , Enfermedad de Crohn/genética , Estudio de Asociación del Genoma Completo , Predisposición Genética a la Enfermedad , Sitios Genéticos , Polimorfismo de Nucleótido Simple/genética , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/genética , Proteínas Portadoras/genética , Proteínas de la Membrana/genética , Proteasas Ubiquitina-Específicas/genéticaRESUMEN
Genome-wide association studies (GWAS) of Crohn's disease (CD) in European and leprosy in Chinese population have shown that CD and leprosy share genetic risk loci. As these shared loci were identified through cross-comparisons across different ethnic populations, we hypothesized that meta-analysis of GWAS on CD and leprosy in East Asian populations would increase power to identify additional shared loci. We performed a cross-disease meta-analysis of GWAS data from CD (1621 cases and 4419 controls) and leprosy (2901 cases 3801 controls) followed by replication in additional datasets comprising 738 CD cases and 488 controls and 842 leprosy cases and 925 controls. We identified one novel locus at 7p22.3, rs77992257 in intron 2 of ADAP1, shared between CD and leprosy with genome-wide significance (P = 3.80 × 10-11) and confirmed 10 previously established loci in both diseases: IL23R, IL18RAP, IL12B, RIPK2, TNFSF15, ZNF365-EGR2, CCDC88B, LACC1, IL27, NOD2. Phenotype variance explained by the polygenic risk scores derived from Chinese leprosy data explained up to 5.28% of variance of Korean CD, supporting similar genetic structures between the two diseases. Although CD and leprosy shared a substantial number of genetic susceptibility loci in East Asians, the majority of shared susceptibility loci showed allelic effects in the opposite direction. Investigation of the genetic correlation using cross-trait linkage disequilibrium score regression also showed a negative genetic correlation between CD and leprosy (rg [SE] = -0.40[0.13], P = 2.6 × 10-3). These observations implicate the possibility that CD might be caused by hyper-sensitive reactions toward pathogenic stimuli.
Asunto(s)
Enfermedad de Crohn , Lepra , Humanos , Estudio de Asociación del Genoma Completo , Enfermedad de Crohn/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple/genética , Pueblo Asiatico/genética , Sitios Genéticos , Lepra/genética , Estudios de Casos y Controles , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/genéticaRESUMEN
Crohn's disease (CD) is a chronic inflammatory disorder affecting the bowel wall. Tissue-resident memory T (Trm) cells are implicated in CD, yet their characteristics remain unclear. We aimed to investigate the transcriptional profiles and functional characteristics of Trm cells in the small bowel of CD and their interactions with immune cells. Seven patients with CD and four with ulcerative colitis as controls were included. Single-cell RNA sequencing and paired T cell receptor sequencing assessed T cell subsets and transcriptional signatures in lamina propria (LP) and submucosa/muscularis propria-enriched fractions (SM/MP) from small bowel tissue samples. We detected 58,123 T cells grouped into 16 populations, including the CD4+ Trm cells with a Th17 signature and CD8+ Trm clusters. In CD, CD4+ Trm cells with a Th17 signature, termed Th17 Trm, showed significantly increased proportions within both the LP and SM/MP areas. The Th17 Trm cluster demonstrated heightened expression of tissue-residency marker genes (ITGAE, ITGA1, and CXCR6) along with elevated levels of IL17A, IL22, CCR6, and CCL20. The clonal expansion of Th17 Trm cells in CD was accompanied by enhanced transmural dynamic potential, as indicated by significantly higher migration scores. CD-prominent Th17 Trm cells displayed an increased interferon gamma (IFNγ)-related signature possibly linked with STAT1 activation, inducing chemokines (i.e., CXCL10, CXCL8, and CXCL9) in myeloid cells. Our findings underscored the elevated Th17 Trm cells throughout the small bowel in CD, contributing to disease pathogenesis through IFNγ induction and subsequent chemokine production in myeloid cells.
Asunto(s)
Enfermedad de Crohn , Memoria Inmunológica , Células T de Memoria , Células Th17 , Humanos , Enfermedad de Crohn/inmunología , Enfermedad de Crohn/genética , Enfermedad de Crohn/patología , Células Th17/inmunología , Células Th17/metabolismo , Células T de Memoria/inmunología , Células T de Memoria/metabolismo , Masculino , Femenino , Adulto , Persona de Mediana Edad , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Biomarcadores , Perfilación de la Expresión Génica , Adulto JovenRESUMEN
BACKGROUND AND AIM: The anti-interleukin-23 antibody risankizumab is being investigated as a treatment for moderate-to-severe Crohn's disease. This post hoc subanalysis evaluates the efficacy and safety of risankizumab therapy in Asian patients. METHODS: ADVANCE (NCT03105128) and MOTIVATE (NCT03104413) were randomized, double-blind, placebo-controlled, phase 3 induction studies. Patients with intolerance/inadequate response to biologic (MOTIVATE) and/or conventional therapy (ADVANCE) were randomized to receive intravenous risankizumab (600 or 1200 mg) or placebo at weeks 0, 4, and 8. Clinical responders to risankizumab could enter the phase 3, randomized, double-blind, placebo-controlled maintenance withdrawal study (FORTIFY; NCT03105102). Patients were rerandomized to receive subcutaneous risankizumab (180 or 360 mg) or placebo (withdrawal) every 8 weeks for 52 weeks. RESULTS: Among 198 Asian patients in the induction studies, clinical remission and endoscopic response at week 12 were achieved by 61.4% and 40.0%, 59.5% and 35.8%, and 27.3% and 9.1% of patients in the risankizumab 600 mg, risankizumab 1200 mg, and placebo groups, respectively. Among 67 patients who entered the maintenance study, clinical remission and endoscopic response at week 52 were achieved by 57.1% and 52.4%, 75.0% and 40.0%, and 53.8% and 34.6% of patients in the risankizumab 180 mg, risankizumab 360 mg, and placebo (withdrawal) groups, respectively. Fistula closure was observed with risankizumab treatment in 28.6% (induction) and 57.1% (maintenance) of patients. Efficacy trends and safety profile were similar to those in non-Asian patients. CONCLUSION: Consistent with non-Asian and global population results, risankizumab was effective and well tolerated in Asian patients with Crohn's disease.
Asunto(s)
Enfermedad de Crohn , Humanos , Enfermedad de Crohn/tratamiento farmacológico , Anticuerpos Monoclonales/efectos adversos , Inducción de Remisión , Interleucina-23/uso terapéutico , Método Doble Ciego , Resultado del TratamientoRESUMEN
Inflammatory bowel disease (IBD) is rapidly emerging in the Asia Pacific region. However, there are many challenges in the diagnosis and management of this condition. The Asian Pacific Association of Gastroenterology (APAGE) Working Group on IBD conducted a round table meeting to identify 10 common mistakes in the management of IBD in Asia. To summarize, many physicians still over rely on a definitive histological diagnosis before starting treatment and do not fully establish disease extent such as perianal and proximal gastrointestinal involvement in Crohn's disease (CD) or extent of involvement in ulcerative colitis (UC). It is also essential to actively look for evidence of extra-intestinal manifestations, which may influence choice of therapy. In terms of conventional therapy, underuse of topical 5 aminosalicylates (5-ASAs) in UC and inappropriate dosing of corticosteroids are also important considerations. Acute severe UC remains a life-threatening condition and delay in starting rescue therapy after inadequate response to intravenous steroids is still common. Anti-tumor necrosis factors should be considered first line in all cases of complex perianal fistulizing CD. Most patients with IBD are on potent immunosuppressive therapy and should be screened for latent infections and offered vaccinations according to guidelines. Under-recognition and management of significant complications such as anemia, osteoporosis, malnutrition, and thromboembolism should also be addressed. Colonoscopy is still not properly performed for dysplasia/cancer surveillance and for evaluating post-op recurrence of CD. Another common misstep is inappropriate withdrawal of medications during pregnancy leading to increased complications for the mother and the newborn.
Asunto(s)
Gastroenterología , Enfermedades Inflamatorias del Intestino , Humanos , Asia/epidemiología , Gastroenterología/normas , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/terapia , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/terapia , Femenino , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/terapia , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Inmunosupresores/administración & dosificación , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Embarazo , Mesalamina/uso terapéutico , Mesalamina/administración & dosificaciónRESUMEN
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Genetic association studies have identified the highly variable human leukocyte antigen (HLA) region as the strongest susceptibility locus for IBD and specifically DRB1*01:03 as a determining factor for ulcerative colitis (UC). However, for most of the association signal such as delineation could not be made because of tight structures of linkage disequilibrium within the HLA. The aim of this study was therefore to further characterize the HLA signal using a transethnic approach. We performed a comprehensive fine mapping of single HLA alleles in UC in a cohort of 9272 individuals with African American, East Asian, Puerto Rican, Indian and Iranian descent and 40 691 previously analyzed Caucasians, additionally analyzing whole HLA haplotypes. We computationally characterized the binding of associated HLA alleles to human self-peptides and analyzed the physicochemical properties of the HLA proteins and predicted self-peptidomes. Highlighting alleles of the HLA-DRB1*15 group and their correlated HLA-DQ-DR haplotypes, we not only identified consistent associations (regarding effects directions/magnitudes) across different ethnicities but also identified population-specific signals (regarding differences in allele frequencies). We observed that DRB1*01:03 is mostly present in individuals of Western European descent and hardly present in non-Caucasian individuals. We found peptides predicted to bind to risk HLA alleles to be rich in positively charged amino acids. We conclude that the HLA plays an important role for UC susceptibility across different ethnicities. This research further implicates specific features of peptides that are predicted to bind risk and protective HLA proteins.
Asunto(s)
Colitis Ulcerosa/genética , Etnicidad/genética , Predisposición Genética a la Enfermedad , Antígenos HLA/genética , Antígenos HLA-DQ/genética , Cadenas HLA-DRB1/genética , Péptidos/genética , Alelos , Estudios de Cohortes , Frecuencia de los Genes , Estudios de Asociación Genética , Genotipo , Haplotipos , Humanos , Desequilibrio de Ligamiento , Polimorfismo de Nucleótido Simple , Unión ProteicaRESUMEN
BACKGROUND: There are few studies analyzing the cost of endoscopic resection and surgical resection in the treatment of submucosal colorectal cancer. OBJECTIVE: The objective was to perform a detailed cost analysis of endoscopic resection and surgical resection for submucosal colorectal cancer. DESIGN: This was a retrospective observational study. SETTING: This study was conducted at a tertiary academic center. PATIENTS: Medical records of 484 patients with submucosal colorectal cancer who underwent endoscopic resection or surgical resection between July 2003 and July 2015 were reviewed. MAIN OUTCOME MEASUREMENTS: The total costs during index admission and follow-up as well as clinical outcomes between the 2 groups were compared in the whole cohort and propensity score-matched cohort. RESULTS: In the propensity score-matched analysis ( n = 155 in each group), the endoscopic resection and surgical resection groups did not show significant differences in the rates of procedure-related adverse events (6.5% vs 3.9%; p = 0.304) and recurrence (0.6% vs 1.3%; p > 0.99). Readmission was more common in the endoscopic resection group (40.6% vs 11.0%; p < 0.001) because 64 (41.3%) patients underwent additional surgery for endoscopic noncurative resection. The endoscopic resection group had a lower cost during the index admission (1335.6 vs 6698.4 USD; p < 0.001), whereas the surgical resection group had a lower cost during follow-up (2488.7 vs 5035.7 USD; p < 0.001). The total cumulative cost was lower in the endoscopic resection group (6371.3 vs 9187.1 USD; p < 0.001). The same trend was observed in the whole cohort without propensity score matching. LIMITATIONS: A limitation of this study was the retrospective nature of analysis. CONCLUSIONS: The total cumulative cost for treatment and follow-up for submucosal colorectal cancer was lower in the endoscopic resection group, which had comparable oncologic outcomes as the surgical resection group. Endoscopic resection can be considered a cost-effective option for initial treatment for submucosal colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B881 . ANLISIS COMPARATIVO DE COSTOS ENTRE LA RESECCIN ENDOSCPICA Y LA CIRUGA PARA EL CNCER COLORRECTAL SUBMUCOSO: ANTECEDENTES: Existen pocos estudios que analizan el costo de la resección endoscópica y la resección quirúrgica en el tratamiento del cáncer colorrectal submucoso.OBJETIVO: El objetivo fue realizar un análisis detallado de costos tanto de la resección endoscópica y la resección quirúrgica para el cáncer colorrectal submucoso.DISEÑO: Este fue un estudio observacional retrospectivo.AJUSTE: Este estudio se realizó en un centro académico terciario.PACIENTES: Se revisaron las historias clínicas de 484 pacientes con cáncer colorrectal submucoso que fueron sometidos a resección endoscópica o resección quirúrgica entre julio de 2003 y julio de 2015.PRINCIPALES MEDICIONES DE RESULTADOS: Los costos totales durante la admisión índice y el seguimiento, así como los resultados clínicos entre los dos grupos, fueron comparados en toda la cohorte y la cohorte emparejada por puntuación de propensión.RESULTADOS: En el análisis emparejado por puntuación de propensión ( n = 155 en cada grupo), los grupos de resección endoscópica y resección quirúrgica no mostraron diferencias significativas en las tasas de eventos adversos relacionados con el procedimiento (6,5% vs 3,9%, p = 0,304) y recurrencia (0,6% vs 1,3%, p > 0,99). La readmisión fue más común en el grupo de resección endoscópica (40,6% vs 11,0%, p < 0,001) porque 64 (41,3%) pacientes fueron sometidos a una cirugía adicional para lograr la resección en aquellos casos en que la resección endoscópica no fue curativa. El grupo de resección endoscópica tuvo un costo menor durante el ingreso índice (1335.6 vs 6698.4 USD, p < 0.001), mientras que el grupo de resección quirúrgica tuvo un costo menor durante el seguimiento (2488.7 vs 5035.7 USD, p < 0.001). El costo total acumulado fue menor en el grupo de resección endoscópica (6371,3 vs 9187,1 USD, p < 0,001). La misma tendencia se observó en toda la cohorte sin emparejamiento por puntuación de propensión.LIMITACIONES: La naturaleza retrospectiva del análisis.CONCLUSIONES: El costo total acumulado para el tratamiento y seguimiento del cáncer colorrectal submucoso fue menor en el grupo de resección endoscópica, que tuvo resultados oncológicos comparables a los del grupo de resección quirúrgica. La resección endoscópica puede considerarse una opción rentable para el tratamiento inicial del cáncer colorrectal submucoso. Consulte Video Resumen en http://links.lww.com/DCR/B881 . (Traducción-Dr Osvaldo Gauto ).
Asunto(s)
Neoplasias del Recto , Humanos , Estudios Retrospectivos , Neoplasias del Recto/cirugía , Costos y Análisis de CostoRESUMEN
BACKGROUND: Intestinal Behçet's disease (BD) is characterized by typical gastrointestinal ulcers in patients with BD followed by complications such as bleeding, perforation and fistula. Biologic agents are currently under active investigation to delay the disease course. Various data regarding infliximab are available, but there is relatively lack of data regarding adalimumab. METHODS: This was a multicenter, real-world prospective observational study to evaluate the effectiveness and safety of adalimumab in intestinal BD. The primary endpoint was disease activity at each follow up, including disease activity index for intestinal Behçet's disease (DAIBD), serum C-reactive protein (CRP) level, and endoscopic findings. The secondary endpoint was the incidence of adverse drug reactions (ADRs). RESULTS: A total of 58 patients were enrolled and 8 of them were excluded. Adverse events were reported in 72.0% of patients with 122 events. ADRs were reported in 24.0% with 28 events. For adverse events, arthralgia was most commonly reported (13.1%: 16/122) and only one experienced critical adverse event (0.82%, 1/122: death due to stroke). On multivariable regression analysis, a longer disease duration was significantly associated with decreased ADRs [Odds ratio 0.976 (0.953-0.999, 95% CI); p = 0.042]. Clinical response rates as assessed by DAIBD were 90.9% at Week 12 and 89.7% at Week 56, respectively. The mean serum CRP level at baseline was significantly decreased after 12 weeks (3.91 ± 4.93 to 1.26 ± 2.03 mg/dL; p = 0.0002). CONCLUSION: Adalimumab was found to be safe and effective in Korean patients with intestinal BD. A longer disease duration was significantly associated with decreased ADRs.
Asunto(s)
Síndrome de Behçet , Enfermedades Intestinales , Humanos , Adalimumab/efectos adversos , Síndrome de Behçet/complicaciones , Síndrome de Behçet/tratamiento farmacológico , Intestinos , Infliximab , Enfermedades Intestinales/tratamiento farmacológico , Enfermedades Intestinales/inducido químicamenteRESUMEN
BACKGROUND: Many patients with ulcerative colitis (UC) gain weight after treatment. However, the clinical significance of weight gain in these patients remains unclear. This study aimed to evaluate body weight changes after treatment in patients newly diagnosed with moderate-to-severe UC and their effects on patients' prognosis. METHODS: The change in weight between diagnosis and 1 year after treatment in 212 patients enrolled in the MOSAIK cohort (mean age, 40 years; males, 60%) was analyzed. Significant weight gain was defined as a weight increase of ≥ 5% from the baseline at 1 year. Factors associated with significant weight gain and the effect of significant weight gain on the risk of major adverse outcomes (clinical relapse, hospitalization, and new use of steroids or biologics) during a follow-up period of 20 months were evaluated. RESULTS: Mean weight gain at 1 year was 1.7 ± 4.2 kg. The proportion of overweight/obese patients increased by 9.0% from 37.9% to 46.9%. Thirty-two percent had significant weight gain; extensive colitis at diagnosis was the only factor associated with significant weight gain (odds ratio 6.5, 95% confidence interval 1.4-31.0, p = 0.006). In multivariable analysis, significant weight gain was not associated with the risk of major adverse outcomes. Weight loss symptoms at diagnosis were associated with an increased risk for new steroid use after 1 year. CONCLUSIONS: Approximately one-third of patients with moderate-to-severe UC had significant weight gain after 1 year of treatment. However, significant weight gain was not associated with the patient's prognosis.
Asunto(s)
Colitis Ulcerosa , Masculino , Humanos , Adulto , Colitis Ulcerosa/complicaciones , Relevancia Clínica , Pronóstico , Aumento de Peso , República de Corea/epidemiología , Estudios RetrospectivosRESUMEN
BACKGROUND AND AIM: Low-volume bowel preparation solutions, including 1-L polyethylene glycol plus ascorbate (PEG-A), have been developed to improve tolerability. The oral sodium sulfate tablet (OST) is a new agent with simethicone as a preloaded component. We investigated the efficacy, safety, and tolerability of OST compared to 1-L PEG-A. METHODS: A single-center, prospective, controlled study was performed with randomization into the OST (group A) and 1-L PEG-A (group B) groups. Bowel preparation efficacy was assessed on the Boston Bowel Preparation Scale (BBPS) and Bubble Scale. Safety and tolerability were evaluated using a questionnaire and laboratory examination. RESULTS: Final analysis was performed on 171 patients (group A: 87, group B: 84). The proportion of bowel preparation success (BBPS ≥ 2 for each colonic segment) in group A was not inferior compared to group B (95.4% vs 96.4%, P = 0.736, 1-sided 97.5% lower confidence limit -7.0%). The adenoma detection rate was not different (59.6% vs 41.9%; P = 0.087). The bubble scale was better in group A (0.2 ± 0.9 vs 1.9 ± 1.7, P < 0.001). All adverse events were mild in both groups. Nausea was less frequent in group A (14.9% vs 38.1%, P = 0.001). Overall satisfaction was better in group A (8.1 ± 2.1 vs 6.4 ± 2.8, P < 0.001). No clinically significant laboratory abnormality developed in both groups. These findings were similarly shown in old patients ≥65 years. CONCLUSIONS: Both OST and 1-L PEG-A were efficacious, safe, and tolerable for bowel preparation of colonoscopy. The OST showed fewer bubbles and slightly better tolerability.
Asunto(s)
Catárticos , Polietilenglicoles , Humanos , Polietilenglicoles/efectos adversos , Estudios Prospectivos , Catárticos/efectos adversos , Colon , Colonoscopía , Ácido Ascórbico/efectos adversosRESUMEN
BACKGROUND AND AIM: This study aimed to investigate the effect of stenting-related factors, including endoscopists' expertise, on clinical outcomes after bridge-to-surgery (BTS) stenting for obstructive colorectal cancer (CRC). METHODS: We analyzed BTS stenting-related factors, including stenting expertise and the interval between stenting and surgery, in 233 patients (63 [13] years, 137 male) who underwent BTS stenting for obstructive CRC. We evaluated the influence of these factors on post-BTS stenting clinical outcomes such as stent-related complications and cancer recurrence. RESULTS: The interval between stenting and surgery was ≤ 7 days in 79 patients (33.9%) and > 7 days in 154 patients (66.1%). BTS stenting was performed by endoscopists with ≤ 50, 51-100, and > 100 prior stenting experiences in 94, 43, and, 96 patients, respectively. The clinical success rate of BTS stenting was 93.1%. Stent-related and postoperative complications developed in 19 (8.2%) and 20 (8.6%) patients, respectively. Cancer recurrence occurred in 76 patients (32.6%). Short BTS interval of ≤ 7 days increased the risk of postoperative complications (odds ratio [OR], 2.61 [1.03-6.75]; P = 0.043). Endoscopists' stenting experience > 100 showed greater clinical success of stenting (OR, 5.50 [1.45-28.39]; P = 0.021) and fewer stent-related complications (OR, 0.26 [0.07-0.80]; P = 0.028) compared with stenting experience ≤ 50. BTS stenting-related factors did not affect long-term oncological outcomes. CONCLUSION: Greater expertise of endoscopists was associated with better short-term outcomes, including high stenting success rate and low rate of stent-related complications after BTS stenting for obstructive CRC. An interval of > 7 days between BTS stenting and surgery was required to decrease postoperative complications.
Asunto(s)
Neoplasias Colorrectales , Obstrucción Intestinal , Humanos , Masculino , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/complicaciones , Recurrencia Local de Neoplasia/complicaciones , Stents/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Obstrucción Intestinal/etiología , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
BACKGROUND AND AIMS: Reduced body muscle mass is a poor prognostic factor for inflammatory bowel disease (IBD). In this study, we investigated the prevalence of sarcopenia at diagnosis and its clinical significance in Korean patients with IBD. METHODS: The prevalence of sarcopenia in IBD patients between June 1989 and December 2016 was investigated using a well-characterized referral center-based cohort. Abdominopelvic computed tomography within six months from IBD diagnosis was used for the evaluation. Sarcopenia was defined as an L3 skeletal muscle index of < 49 cm2/m2 for male and < 31 cm2/m2 for female. The clinical characteristics and outcomes were evaluated with respect to sarcopenia. RESULTS: A total of 1,027 patients (854 Crohn's disease [CD]; 173 ulcerative colitis [UC]) were evaluated. Sarcopenia was found in 56.8% of the population (CD, 57.5%; UC, 53.2%), and male were more likely to be sarcopenic (CD, 94.3%; UC, 91.6%). There were no significant differences in the cumulative risk of using steroids, immunomodulators, biologics, and bowel resections (or colectomy) with or without sarcopenia during follow-up (median: CD, 5.8 years; UC, 3.7 years). In sarcopenic patients with CD, there was a significantly higher cumulative risk of perianal surgeries than in non-sarcopenic patients with CD (Log-rank test; P = 0.001). However, the risk of perianal surgeries was not significant in multivariate analysis (Odds ratio 1.368; 95% confidence interval 0.782-2.391; P = 0.272). CONCLUSION: Sarcopenia at diagnosis may have no significant prognostic value for medical treatment and bowel resection, but it may be associated with perianal CD.
Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Sarcopenia , Humanos , Masculino , Femenino , Sarcopenia/diagnóstico por imagen , Sarcopenia/epidemiología , Enfermedades Inflamatorias del Intestino/diagnóstico , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/epidemiología , Colectomía , Progresión de la Enfermedad , República de Corea/epidemiologíaRESUMEN
OBJECTIVES: High-contrast and high-resolution imaging techniques would enable real-time sensitive detection of the gastrointestinal lesions. This study aimed to investigate the feasibility of novel dual fluorescence imaging using moxifloxacin and proflavine in the detection of neoplastic lesions of the human gastrointestinal tract. METHODS: Patients with the colonic and gastric neoplastic lesions were prospectively enrolled. The lesions were biopsied with forceps or endoscopically resected. Dual fluorescence imaging was performed by using custom axially swept wide-field fluorescence microscopy after topical moxifloxacin and proflavine instillation. Imaging results were compared with both confocal imaging with cell labeling and conventional histological examination. RESULTS: Ten colonic samples (one normal mucosa, nine adenomas) from eight patients and six gastric samples (one normal mucosa, five adenomas) from four patients were evaluated. Dual fluorescence imaging visualized detail cellular structures. Regular glandular structures with polarized cell arrangement were observed in normal mucosa. Goblet cells were preserved in normal colonic mucosa. Irregular glandular structures with scanty cytoplasm and dispersed elongated nuclei were observed in adenomas. Goblet cells were scarce or lost in the colonic lesions. Similarity analysis between moxifloxacin and proflavine imaging showed relatively high correlation values in adenoma compared with those in normal mucosa. Dual fluorescence imaging showed good detection accuracies of 82.3% and 86.0% in the colonic and the gastric lesions, respectively. CONCLUSIONS: High-contrast and high-resolution dual fluorescence imaging was feasible for obtaining detail histopathological information in the gastrointestinal neoplastic lesions. Further studies are needed to develop dual fluorescence imaging as an in vivo real-time visual diagnostic method.
Asunto(s)
Adenoma , Proflavina , Humanos , Moxifloxacino , Estudios Prospectivos , Estudios de Factibilidad , Adenoma/patología , Imagen ÓpticaRESUMEN
BACKGROUND & AIMS: In this nationwide population-based study, we investigated the risk of vertebral and hip fractures in patients with inflammatory bowel disease (IBD). METHODS: Using data from the Korean National Health Insurance claims database gathered between 2007 and 2016, we calculated the incidence rate ratios (IRRs) of vertebral and hip fractures in patients with newly diagnosed IBD (n = 18,228; 64.1% male, 65.9% ulcerative colitis) compared with an age- and sex-matched control population (matching ratio, 1:10; n = 186,871). RESULTS: During a median follow-up period of 4.5 years, the incidence rate and IRR of vertebral and hip fractures in patients with IBD were 2.88 per 1000 person-years and 1.24 (95% CI, 1.08-1.42), respectively. The cumulative risk of vertebral and hip fractures in IBD patients was 0.6%, 1.4%, and 1.9% at 2, 5, and 7 years after diagnosis, respectively, and this risk of fracture in IBD patients was higher than that in matched controls (P = .002). The use of corticosteroids further increased the risk of fractures in IBD patients (IRR, 1.37; 95% CI, 1.13-1.65) compared with matched controls. The risk of fractures was significantly higher in patients with Crohn's disease (CD) (IRR, 1.56; 95% CI, 1.19-2.04) than in matched controls, and this risk remained higher in patients with CD without corticosteroid exposure (IRR, 1.62; 95% CI, 1.12-2.34). The risk of fracture increased with age and was particularly high in females and in those with comorbidities. CONCLUSIONS: The risk of fractures was significantly high in newly diagnosed IBD patients, especially in those with CD regardless of corticosteroid exposure.
Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Fracturas de Cadera , Enfermedades Inflamatorias del Intestino , Corticoesteroides , Estudios de Casos y Controles , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/epidemiología , Femenino , Fracturas de Cadera/epidemiología , Fracturas de Cadera/etiología , Humanos , Incidencia , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/epidemiología , Masculino , Factores de RiesgoRESUMEN
BACKGROUND & AIMS: This study compared pharmacokinetics, symptomatic and endoscopic efficacy, safety, and immunogenicity of a subcutaneous formulation of the infliximab biosimilar CT-P13 (CT-P13 SC) vs intravenous CT-P13 (CT-P13 IV) in patients with inflammatory bowel disease (IBD). METHODS: This randomized, multicenter, open-label, parallel-group, phase 1 study enrolled tumor necrosis factor inhibitor-naïve patients with active ulcerative colitis (total Mayo score 6-12 points with endoscopic subscore ≥2) or Crohn's disease (Crohn's Disease Activity Index 220-450 points) at 50 centers. After CT-P13 IV induction at Week (W) 0/W2, patients were randomized (1:1) to receive CT-P13 SC every 2 weeks (q2w) from W6 to W54 or CT-P13 IV every 8 weeks from W6 to W22. At W30, all patients receiving CT-P13 IV switched to CT-P13 SC q2w until W54. The primary endpoint was noninferiority of CT-P13 SC to CT-P13 IV for observed predose CT-P13 concentration at W22 (Ctrough,W22), concluded if the lower bound of the 2-sided 90% confidence interval (CI) for the ratio of geometric least-squares means exceeded 80%. RESULTS: Overall, 66 and 65 patients were randomized to CT-P13 SC and CT-P13 IV, respectively. The primary endpoint of noninferiority was met with a geometric least-squares means ratio for Ctrough,W22 of 1154.17% (90% CI 786.37-1694.00; n = 59 [CT-P13 SC]; n = 57 [CT-P13 IV]). W30/W54 clinical remission rates were comparable between arms. Other efficacy, safety, and immunogenicity assessments were also broadly comparable between arms, including after switching. CONCLUSIONS: The pharmacokinetic noninferiority of CT-P13 SC to CT-P13 IV, and the comparable efficacy, safety, and immunogenicity profiles, support the potential suitability of CT-P13 SC treatment in IBD. ClinicalTrials.gov ID: NCT02883452.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Biosimilares Farmacéuticos/administración & dosificación , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Fármacos Gastrointestinales/administración & dosificación , Administración Intravenosa , Adolescente , Adulto , Anciano , Proteína C-Reactiva/efectos de los fármacos , Colitis Ulcerosa/metabolismo , Enfermedad de Crohn/metabolismo , Sustitución de Medicamentos , Heces/química , Femenino , Humanos , Infliximab/administración & dosificación , Infliximab/sangre , Inyecciones Subcutáneas , Complejo de Antígeno L1 de Leucocito/efectos de los fármacos , Quimioterapia de Mantención , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND AND AIMS: WingCap (A&A Medical Supply LLC, Seongnam, South Korea) is a novel distal attachment device for colonoscopy that combines a cap and an existing mucosal exposure device, such as Endocuff Vision (Arc Medical Design Ltd, Leeds, UK) and AmplifEYE (Medivators Inc, Minneapolis, Minn, USA). We aimed to investigate whether WingCap-assisted colonoscopy can improve the adenoma detection rate (ADR) and adenoma per colonoscopy (APC) and simultaneously shorten cecal intubation time compared with standard colonoscopy. METHODS: We conducted a single-center, prospective, randomized controlled trial for outpatients aged ≥18 years undergoing colonoscopy. The primary outcome was ADR differences with the assistance of WingCap. Secondary outcomes were APC and other colonoscopy quality indicators, such as cecal intubation and withdrawal times. RESULTS: In total, 537 patients were randomized for WingCap-assisted or standard colonoscopy. Their mean age was 59.3 years, and 48.5% were men. ADR was significantly higher in the WingCap group than in the control group (37.2% vs 26.6%, P = .012). APC was greater with WingCap than with standard colonoscopy (.72 ± 1.34 vs .45 ± 0.97, P = .008), prominently for nonpedunculated (.65 ± 1.25 vs .42 ± .95, P = .015) and diminutive (.42 ± .94 vs .20 ± .64, P = .002) adenomas. With WingCap, ADR and APC significantly increased for beginner endoscopists, whereas a modest increase was seen for experienced endoscopists. There were no differences in cecal intubation and withdrawal times between the 2 arms. No serious adverse event was associated with the use of WingCap. CONCLUSIONS: WingCap-assisted colonoscopy was tolerable and efficacious for improving ADR and APC compared with standard colonoscopy, especially for nonpedunculated and diminutive adenomas and for beginner endoscopists. (Clinical trial registration number: KCT0005214.).
Asunto(s)
Adenoma , Neoplasias Colorrectales , Adenoma/diagnóstico por imagen , Adenoma/etiología , Adolescente , Adulto , Ciego , Colonoscopios , Colonoscopía/efectos adversos , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND AND AIM: Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We present safety and efficacy data from patients from East Asia (Japan, Korea, and Taiwan) in OCTAVE Open, an open-label, long-term extension study. METHODS: Patients in remission at OCTAVE Open baseline received tofacitinib 5 mg twice daily (BID); all others received tofacitinib 10 mg BID. Proportions and IRs (unique patients with events/100 patient-years) were calculated for adverse events (AEs) of special interest. Efficacy endpoints were evaluated up to 36 months. RESULTS: In OCTAVE Open, 105/944 patients were from East Asia (tofacitinib 5 mg BID, n = 22; tofacitinib 10 mg BID, n = 83). Overall, 87.6% and 24.8% of patients had AEs and serious AEs, respectively; IRs (95% CI) for AEs of special interest were herpes zoster (HZ; non-serious and serious), 6.07 (3.40-10.02); serious infections, 1.47 (0.40-3.76); opportunistic infections, 1.91 (0.62-4.45); major cardiovascular adverse events, 0.37 (0.01-2.04); malignancies (excluding non-melanoma skin cancer [NMSC]), 0.37 (0.01-2.04); and NMSC, 0.00 (0.00-1.35). No deaths, venous thromboembolic events, or gastrointestinal perforations occurred. At month 36, 68.2% and 54.2% of patients had a clinical response, 68.2% and 53.0% had endoscopic improvement, and 63.6% and 49.4% were in remission with tofacitinib 5 and 10 mg BID, respectively. CONCLUSIONS: The HZ IR in East Asian patients was numerically higher versus the global study population; excluding HZ, tofacitinib safety and efficacy were consistent with the global study population.
Asunto(s)
Colitis Ulcerosa , Inhibidores de las Cinasas Janus , Humanos , Inhibidores de las Cinasas Janus/efectos adversos , Inhibidores de las Cinasas Janus/uso terapéutico , Piperidinas , Pirimidinas , Pirroles , Resultado del TratamientoRESUMEN
BACKGROUND AND AIM: Evidence has emerged that a pretreatment immune profile in rectal cancer is associated with response to chemoradiotherapy (CRT) and recurrence after CRT. However, few studies have evaluated the immune profile differences after CRT regarding recurrence and nonrecurrence. METHODS: We included patients with advanced rectal cancer treated with CRT and surgery with recurrence within 1 year in a recurrence group. After sex and age matching with the recurrence group, patients with no recurrence for 3 years after CRT were included in a nonrecurrence group. We extracted the immune profile, including CD3 and CD8, from the surgical specimen after CRT using multispectral fluorescence immunohistochemistry and compared the two groups. RESULTS: The immune profiles of 65 patients with rectal cancer were assessed; 30 were included in the recurrence group and 35 were included in the nonrecurrence group. CD3+ and CD8+ T lymphocyte densities were significantly higher in the nonrecurrence group than in the recurrence group (CD3+ ; P < 0.001, CD8+ ; P = 0.003) in the primary tumor. Consistent results were found in epithelial and stromal cells. Compared with the recurrence group, the distinct profiles of co-expressed immune markers in the nonrecurrence group were revealed (CD3+ CD8+ , P = 0.001; CD3+ CD8+ PD-L1- , P = 0.001; CD3+ CD8+ FOXP3- PD-L1- , P = 0.001). CONCLUSIONS: Vigorous CD3+ and CD8+ T cell priming post-CRT was prominent in the nonrecurrence group compared with that of the recurrence group. This finding suggests that differences in immune profiles may have clinical significance even after CRT.
Asunto(s)
Quimioradioterapia , Neoplasias del Recto , Femenino , Humanos , Inmunohistoquímica , Masculino , Recurrencia Local de Neoplasia , Neoplasias del Recto/metabolismo , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Resultado del TratamientoRESUMEN
The present study investigated the risk of active tuberculosis in patients with inflammatory bowel disease (IBD) treated with vedolizumab or ustekinumab, in actual clinical settings in a country with an intermediate tuberculosis burden. The medical records of 238 patients with IBD who received vedolizumab or ustekinumab were retrospectively reviewed at a tertiary referral center in South Korea. All patients had ≥ 3 months of follow-up duration and underwent a latent tuberculosis infection screening test before initiation of the administration of these drugs. Of the 238 patients enrolled, 181 had Crohn's disease, and 57 had ulcerative colitis. During the median 18.7 months of follow-up, active tuberculosis did not develop in any patient treated with vedolizumab or ustekinumab. Therefore, we concluded that the risk of tuberculosis appears to be low in patients with IBD treated with vedolizumab or ustekinumab in South Korea.
Asunto(s)
Enfermedades Inflamatorias del Intestino , Tuberculosis , Anticuerpos Monoclonales Humanizados , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Estudios Retrospectivos , Resultado del Tratamiento , Tuberculosis/complicaciones , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Ustekinumab/efectos adversosRESUMEN
OBJECTIVES: Post-polypectomy surveillance intervals should be determined based on index colonoscopy findings. However, the risk of metachronous lesions, resulting from the coexistence of adenoma and sessile serrated lesions (SSLs), has rarely been addressed. We evaluated the impact of synchronous SSL on the risk of metachronous lesions within similar adenoma risk groups. METHODS: We retrieved individuals with one or more adenomas on index colonoscopy in a single-center retrospective cohort and stratified them into four groups depending on the presence of SSL and low-risk/high-risk adenoma (LRA/HRA). Participants who underwent surveillance colonoscopies at least 12 months apart were included. We compared the risks of metachronous lesions including HRA, advanced adenoma (AA), or SSL within similar adenoma risk groups according to the presence of SSL. RESULTS: Overall 4493 individuals were included in the analysis. The risk of metachronous HRA/AA was not significantly higher in the adenoma with SSL group compared with the adenoma without SSL group, irrespective of LRA (HRA, 6/86 vs. 231/3297, P = 1.00; AA, 0/86 vs. 52/3297, P = 0.64) or HRA (HRA, 11/64 vs. 240/1046, P = 0.36; AA, 3/64 vs. 51/1046, P = 1.00). However, the risk of metachronous SSL in individuals with synchronous SSL was higher than that in those without SSL for both LRA (15/86 vs. 161/3297, P < 0.001) and HRA groups (11/64 vs. 61/1046, P = 0.002). CONCLUSION: The presence of synchronous SSL did not increase the risk of metachronous HRA/AA, compared with isolated adenoma, but increased the risk of metachronous SSL.