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The development of premalignant colorectal polyps is significantly influenced by various lifestyle and modifiable risk factors. In our study, we used a large cohort of 9025 patients, who underwent screening colonoscopies at a university hospital, to assess the risk factors associated with the development of three different colorectal cancer precursor lesions: non-advanced adenomas (NAs), advanced adenomatous lesions (ADLs), and sessile serrated lesions (SSLs). Among the participants, 3641 had NAs, 836 had ADLs, and 533 had SSLs. We identified obesity, current smoking, and appendicular skeletal muscle mass as modifiable lifestyle risk factors that increase the development of NAs and ADLs (all P < 0.05). Furthermore, we found a positive correlation between the degree of obesity and an increased risk of developing NAs and ADLs (all P for trend < 0.001), while non-smoking was associated with a decreased risk (P for trend < 0.001 and 0.003, respectively). Smoking was the only modifiable risk factor for developing SSLs (adjusted odds ratio [aOR] 1.58; 95% confidence interval [CI] 1.20-2.07), and the risk was even higher in patients with metabolic syndrome (aOR 1.71; 95% CI 1.05-2.77). Addressing modifiable lifestyle factors such as smoking and obesity could play an important role in reducing the risk of both non-advanced and advanced adenomatous lesions. Smoking cessation is especially important as it is a significant modifiable risk factor for sessile serrated lesions.
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Adenoma , Colonoscopía , Neoplasias Colorrectales , Humanos , Masculino , Femenino , Persona de Mediana Edad , Factores de Riesgo , Adenoma/epidemiología , Adenoma/etiología , Adenoma/patología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/diagnóstico , Anciano , Obesidad/complicaciones , Fumar/efectos adversos , Detección Precoz del Cáncer , Pólipos del Colon/patología , Pólipos del Colon/epidemiología , Pólipos del Colon/diagnóstico , Lesiones Precancerosas/patología , Lesiones Precancerosas/epidemiologíaRESUMEN
The gut microbial and metabolic characteristics of intestinal Behçet's disease (BD), a condition sharing many clinical similarities with ulcerative colitis (UC) and Crohn's disease (CD), are largely unexplored. This study investigated the gut microbial and metabolic characteristics of intestinal BD as well as potential biomarkers, comparing them with those in UC, CD, and healthy controls. Colon tissue and stool samples from 100 patients (35 UC, 30 CD, and 35 intestinal BD) and 41 healthy volunteers were analyzed using 16S ribosomal RNA sequencing to assess microbial diversity, taxonomic composition, and functional profiling. Plasma metabolomic analyses were performed using gas chromatography and ultra-performance liquid chromatography-mass spectrometry. Results indicated reduced microbial diversity in CD but not in intestinal BD, with intestinal BD showing fewer changes compared to controls yet distinct taxonomic features from UC, CD, and controls. Common alterations across all diseases included a reduction in beneficial bacteria producing short-chain fatty acids. Intestinal BD-specific changes featured a decreased abundance of Bacteroides fragilis. Metabolomic profiles in intestinal BD were similar to those in CD but distinct from those in UC, displaying significant changes in energy metabolism and genetic information processing. This integrative analysis revealed both shared and unique profiles in intestinal BD compared with UC, CD, and controls, advancing our understanding of the distinctive features of these diseases.
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Síndrome de Behçet , Microbioma Gastrointestinal , Metaboloma , Humanos , Síndrome de Behçet/microbiología , Síndrome de Behçet/metabolismo , Masculino , Femenino , Adulto , Persona de Mediana Edad , ARN Ribosómico 16S/genética , Enfermedad de Crohn/microbiología , Enfermedad de Crohn/metabolismo , Metabolómica/métodos , Enfermedades Inflamatorias del Intestino/microbiología , Enfermedades Inflamatorias del Intestino/metabolismo , Biomarcadores , Heces/microbiología , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/metabolismo , Estudios de Casos y ControlesRESUMEN
Background/Aims: Limited knowledge exists regarding the optimal timing and relative advantages of primary surgery compared to medical treatment in ileocecal Crohn's disease (CD). This study aimed to compare long-term outcomes between medication-based treatment versus surgery in newly diagnosed ileocecal CD patients in an Asian population. Methods: Among the 885 patients diagnosed with CD and enrolled in the study site hospital cohort between 1980 and 2013, 93 (10.5%) had ileocecal CD. Patients were categorized into either the surgical or medical remission group based on their initial management strategy that led to remission. The rates of relapse, hospitalization, and surgery after achieving remission were compared using Kaplan-Meier curves. Results: The numbers of patients assigned to surgical and medical remission groups were 15 (17.0%) and 73 (83.0%), respectively. The surgical remission group exhibited a lower relapse rate and longer maintenance of remission (10.7 vs. 3.7 yr; p = 0.017) during a median follow-up of 6.6 years. Hospitalization after the first remission tended to be lower in the surgical remission group (p = 0.054). No cases required repeated intestinal resection after the initial surgical remission, whereas a 23% surgery rate was reported at 5 years after initial medical treatment (p = 0.037). In the multivariable analysis, the initial medication-based treatment was significantly associated with relapse (hazard ratio = 3.23, p = 0.039). Conclusions: In selected cases of localized ileocecal CD, ileocolic resection might be a favorable alternative to medication- based treatment, as it demonstrates a lower relapse rate and longer maintenance of remission.
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The use of endoscopic images for the accurate assessment of ulcerative colitis (UC) severity is crucial to determining appropriate treatment. However, experts may interpret these images differently, leading to inconsistent diagnoses. This study aims to address the issue by introducing a standardization method based on deep learning. We collected 254 rectal endoscopic images from 115 patients with UC, and five experts in endoscopic image interpretation assigned classification labels based on the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scoring system. Interobserver variance analysis of the five experts yielded an intraclass correlation coefficient of 0.8431 for UCEIS scores and a kappa coefficient of 0.4916 when the UCEIS scores were transformed into UC severity measures. To establish a consensus, we created a model that considered only the images and labels on which more than half of the experts agreed. This consensus model achieved an accuracy of 0.94 when tested with 50 images. Compared with models trained from individual expert labels, the consensus model demonstrated the most reliable prediction results.
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BACKGROUND/AIMS: This study aimed to evaluate the characteristics of endoscopic retrograde cholangiopancreatography (ERCP) or endoscopic ultrasonography (EUS)-related adverse events (AEs) that eventually lead to medical disputes or claims on medical professional liability. METHODS: Medical disputes for ERCP/EUS-related AEs filed in the Korea Medical Dispute Mediation and Arbitration Agency between April 2012 and August 2020 were evaluated using corresponding medical records. AEs were categorized into three sections: procedure-related, sedation-related, and safety-related AEs. RESULTS: Among a total of 34 cases, procedure-related AEs were 26 (76.5%; 12 duodenal perforations, 7 post-ERCP pancreatitis, 5 bleedings, 2 perforations combined with post-ERCP pancreatitis); sedation-related AEs were 5 (14.7%; 4 cardiac arrests, 1 desaturation), and safety-related AEs were 5 (8.8%; 1 follow-up loss for stent removal, 1 asphyxia, 1 fall). Regarding clinical outcomes, 20 (58.8%) were fatal and eventually succumbed to AEs. For the types of medical institutions, 21 cases (61.8%) occurred at tertiary or academic hospitals, and 13 (38.2%) occurred at community hospitals. CONCLUSION: The ERCP/EUS-related AEs filed in Korea Medical Dispute Mediation and Arbitration Agency showed distinct features: duodenal perforation was the most frequent AE, and clinical outcomes were fatal, resulting in at least more than permanent physical impairment.
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BACKGROUND/AIMS: There have been little research on the cancer risks of patients with Peutz-Jeghers syndrome (PJS) in Korea. We aimed to investigate the clinical features of PJS patients and their cancer incidence rate. METHODS: Patients with PJS from nine medical centers were enrolled. In those patients diagnosed with cancer, data obtained included the date of cancer diagnosis, the tumor location, and the cancer stage. The cumulative risks of gastrointestinal cancers and extra-gastrointestinal cancers were calculated using the Kaplan-Meier method. RESULTS: A total of 96 PJS patients were included. The median age at diagnosis of PJS was 23.4 years. Cancer developed in 21 of the 96 patients (21.9%). The age of PJS diagnosis was widely distributed (0.9 to 72.4 years). The most common cancers were gastrointestinal cancer (n = 12) followed by breast cancer (n = 6). The cumulative lifetime cancer risk was calculated to be 62.1% at age 60. The cumulative lifetime gastrointestinal cancer risk was 47.1% at age 70. The cumulative lifetime extra- gastrointestinal cancer risk was 40.3% at age 60. CONCLUSION: PJS onset may occur at any age and the risks of gastrointestinal and extra-gastrointestinal cancer are high. Thorough surveillance of PJS patients for malignancies is vital.
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Neoplasias de la Mama , Neoplasias Gastrointestinales , Síndrome de Peutz-Jeghers , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Lactante , Preescolar , Niño , Adolescente , Femenino , Síndrome de Peutz-Jeghers/epidemiología , Síndrome de Peutz-Jeghers/complicaciones , Síndrome de Peutz-Jeghers/diagnóstico , Neoplasias Gastrointestinales/etiología , Neoplasias Gastrointestinales/complicaciones , Riesgo , República de Corea/epidemiologíaRESUMEN
Procedural sedation has become increasingly common in endoscopy. Sedatives and analgesics induce anxiolysis and amnesia. In addition, an appropriate level of sedation is necessary for safe procedures including therapeutic endoscopy. Midazolam and propofol are the most commonly used drugs in sedative endoscopy. In recent years, the need to ascertain the safety and effectiveness of sedation has increased in practice. Therefore, new sedatives and analgesic drugs for optimal sedative endoscopy, have recently emerged. This article reviews the characteristics of sedatives and analgesics, and describes their clinical use in gastrointestinal endoscopy.
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Sedation can resolve anxiety and fear in patients undergoing endoscopy. The use of sedatives has increased in Korea. Appropriate sedation is a state in which the patient feels subjectively comfortable while maintaining the airway reflex for stable spontaneous breathing. The patient should maintain a state of consciousness to the extent that he or she can cooperate with the needs of the medical staff. Despite its benefits, endoscopic sedation has been associated with cardiopulmonary complications. Such cardiopulmonary complications are usually temporary, and most patients recover without sequelae. However, these events may progress to serious complications, such as cardiovascular collapse. Therefore, it is essential to screen high-risk patients before sedation and reduce complications by meticulous monitoring. Additionally, physicians should be familiar with the management of emergencies. The first Korean clinical practice guideline for endoscopic sedation was developed based on previous worldwide guidelines for endoscopic sedation using an adaptation process. The guideline consists of nine recommendations based on a critical review of currently available data and expert consensus when the guideline was drafted. These guidelines should provide clinicians, nurses, medical school students, and policy makers with information on how to perform endoscopic sedation with minimal risk.
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Endoscopía Gastrointestinal , Hipnóticos y Sedantes , Sedación Consciente , Femenino , Humanos , República de CoreaRESUMEN
Sedation can resolve anxiety and fear in patients undergoing endoscopy. The use of sedatives has increased in Korea. Appropriate sedation is a state in which the patient feels subjectively comfortable while maintaining the airway reflex for stable spontaneous breathing. The patient should maintain a state of consciousness to the extent that he or she can cooperate with the needs of the medical staff. Despite its benefits, endoscopic sedation has been associated with cardiopulmonary complications. Cardiopulmonary complications are usually temporary. Most patients recover without sequelae. However, they may progress to serious complications, such as cardiovascular collapse. Therefore, it is essential to screen high-risk patients before sedation and reduce complications by meticulous monitoring. Additionally, physicians should be familiar with the management of emergencies. The first Korean clinical practice guideline for endoscopic sedation was developed based on previous worldwide guidelines for endoscopic sedation using an adaptation process. The guideline consists of nine recommendations based on a critical review of currently available data and expert consensus when the guideline was drafted. These guidelines should provide clinicians, nurses, medical school students, and policy makers with information on how to perform endoscopic sedation with minimal risk.
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Sedación Consciente , Endoscopía Gastrointestinal , Endoscopía Gastrointestinal/efectos adversos , Humanos , Hipnóticos y Sedantes/uso terapéutico , República de CoreaRESUMEN
BACKGROUND/AIMS: Epidemiological data on steroid use in South Korean patients with inflammatory bowel disease (IBD) are limited. We documented the steroid use patterns in these patients, and whether physician education on appropriate steroid use affected these patterns. METHODS: ACTION was an observational cohort study conducted in adults (≥19 years) with IBD. A retrospective chart review was performed at baseline (cohort 1) and 1 year after physician training (cohort 2). Eligible cases with excessive or inappropriate steroid use were identified, along with any associated risk factors. RESULTS: Data were collected during May 2018-July 2019 from patients with Crohn's disease (CD) and ulcerative colitis (UC) in cohort 1 (n=1,685) and cohort 2 (n=1,649). At baseline, 155 patients (9.2%) had received steroids within the previous 12 months, 46 (29.7%) of whom had used steroids excessively, 16 (34.8%) of these having inappropriately used excessive steroids. Although steroid exposure was similar in cohort 1 (9.2%) and cohort 2 (9.7%), the latter comprised fewer excessive steroid users (20.0% vs. 29.7%). Severe disease was associated with excessive steroid use in cases with UC, but not with CD. CONCLUSIONS: Although, overall steroid use was relatively low in South Korean patients with IBD, one-third of steroid users used them excessively, and one-third among these used excessive steroids inappropriately. High disease activity was the main risk factor for excessive steroid use which may potentially be reduced by physician education, especially in cases with UC. Active screening to minimize excessive and inappropriate steroid use through physician education should be considered.
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Sedation can resolve anxiety and fear in patients undergoing endoscopy. The use of sedatives has increased in Korea. Appropriate sedation is a state in which the patient feels subjectively comfortable while maintaining the airway reflex for stable spontaneous breathing. The patient should maintain a state of consciousness to the extent that he or she can cooperate with the needs of the medical staff. Despite its benefits, endoscopic sedation has been associated with cardiopulmonary complications. Cardiopulmonary complications are usually temporary. Most patients recover without sequelae. However, they may progress to serious complications, such as cardiovascular collapse. Therefore, it is essential to screen high-risk patients before sedation and reduce complications by meticulous monitoring. Additionally, physicians should be familiar with the management of emergencies. The first Korean clinical practice guideline for endoscopic sedation was developed based on previous worldwide guidelines for endoscopic sedation using an adaptation process. The guideline consists of nine recommendations based on a critical review of currently available data and expert consensus when the guideline was drafted. These guidelines should provide clinicians, nurses, medical school students, and policy makers with information on how to perform endoscopic sedation with minimal risk.
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Tonsil-derived mesenchymal stem cells (TMSCs) showed therapeutic effects on acute and chronic murine colitis models, owing to their immunomodulatory properties; therefore, we evaluated enhanced therapeutic effects of TMSCs on a murine colitis model using three-dimensional (3D) culture method. The expression of angiogenic factors, VEGF, and anti-inflammatory cytokines, IL-10, TSG-6, TGF-ß, and IDO-1, was significantly higher in the 3D-TMSC-treated group than in the 2D-TMSC-treated group (P < 0.05). At days 18 and 30 after inducing chronic colitis, disease activity index scores were estimated to be significantly lower in the 3D-TMSC-treated group than in the colitis control (P < 0.001 and P < 0.001, respectively) and 2D-TMSC-treated groups (P = 0.022 and P = 0.004, respectively). Body weight loss was significantly lower in the 3D-TMSC-treated group than in the colitis control (P < 0.001) and 2D-TMSC-treated groups (P = 0.005). Colon length shortening was significantly recovered in the 3D-TMSC-treated group compared to that in the 2D-TMSC-treated group (P = 0.001). Histological scoring index was significantly lower in the 3D-TMSC-treated group than in the 2D-TMSC-treated group (P = 0.002). These results indicate that 3D-cultured TMSCs showed considerably higher therapeutic effects in a chronic murine colitis model than those of 2D-cultured TMSCs via increased anti-inflammatory cytokine expression.
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Técnicas de Cultivo Tridimensional de Células , Colitis/terapia , Trasplante de Células Madre Mesenquimatosas , Tonsila Palatina/citología , Animales , Niño , Colitis/inducido químicamente , Colitis/patología , Citocinas/metabolismo , Sulfato de Dextran , Modelos Animales de Enfermedad , Células HEK293 , Humanos , Masculino , Células Madre Mesenquimatosas/citología , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Patients with intestinal Behçet's disease (BD) frequently undergo intestinal resections, which significantly affects postoperative morbidity and mortality. The aim of this study was to identify the association between C-reactive protein (CRP) levels and postoperative outcomes in patients with intestinal BD who underwent surgical bowel resection. METHODS: Patients who were diagnosed with intestinal BD and underwent intestinal surgery due to BD at Severance Hospital between November 2005 and April 2018 were retrospectively investigated. Clinical relapse was defined as a disease activity index of BD (DAIBD) > 40, existence of newly added medications, re-hospitalization, or re-operation related to intestinal BD. The relationship between CRP level and postoperative outcomes was analyzed, and a receiver operating characteristic (ROC) curve was drawn to specify a cut-off value. RESULTS: Ninety patients with intestinal BD were included. Among them, 44 were male (48.9%), and the median age at diagnosis was 38 years (range, 11-69 years). The median total disease follow-up duration was 130 months (range, 3-460 months). Forty patients (44.4%) underwent laparoscopic surgery. A higher CRP level immediately after surgery was significantly associated with postoperative complications (OR 1.01, 95% CI 1.004-1.018, p < 0.01), re-operation (hazard ratio [HR] 1.01, 95% CI 1.005-1.020, p < 0.01), and re-admission (HR 1.01, 95% CI 1.006-1.017 p < 0.01). The ROC curve showed that CRP predicts the risk of postoperative complications (p < 0.01) at a cut-off value of 41.9% with a sensitivity of 60.0% and specificity of 67.7%. CONCLUSIONS: Postoperative CRP levels in patients with intestinal BD undergoing surgical resection were associated with postoperative outcomes.
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Síndrome de Behçet , Proteína C-Reactiva , Enfermedades Intestinales , Adolescente , Adulto , Anciano , Síndrome de Behçet/cirugía , Proteína C-Reactiva/análisis , Niño , Femenino , Humanos , Enfermedades Intestinales/cirugía , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Estudios Retrospectivos , Adulto JovenRESUMEN
Recently in Korea, where triple therapy is accepted as the first-line Helicobacter pylori (H. pylori) eradication treatment, antibiotic resistance to clarithromycin has increased considerably, resulting in eradication rates of less than 80%. We investigated the efficacy of tailored therapy after a clarithromycin resistance test compared with empirical therapy for H. pylori eradication. The cost-effectiveness of H. pylori eradication success was evaluated according to the average medical cost per patient. A total of 364 patients were enrolled in the study. The first-line H. pylori eradication rate was significantly higher in patients who received tailored therapy than in those who received empirical therapy. The total medical costs for the tailored and empirical groups were 46,374 Won and 53,528 Won. The total treatment period for each ultimately successful eradication in the tailored group was 79.8 ± 2.8 days, which is shorter than that of the empirical group (99.2 ± 7.4 days). The rate of eradication-related adverse events for the tailored group and empirical group was 12.9% and 14.8%, respectively. Tailored therapy could be a useful option to achieve a higher successful eradication rate, shorter treatment periods, and lower medical costs than empirical therapy in the era of increasing antibiotic resistance.
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BACKGROUND/AIMS: The tumor necrosis factor-α inhibitors infliximab and adalimumab are standard treatments for moderate to severe ulcerative colitis (UC). However, there has been no headto- head comparison of treatment efficacy and outcomes between the two agents. The aim of this study was to compare the efficacy and long-term outcomes of infliximab versus adalimumab treatment in biologic-naïve patients with UC. METHODS: We retrospectively analyzed the records of 113 biologic-naïve patients with UC who were treated between September 2012 and December 2017 (the infliximab group [n=83] and the adalimumab group [n=30]). We compared remission and response rates between these groups at 8 and 52 weeks. We used Kaplan-Meier curves to compare long-term outcomes, and logistic regression analysis and Cox-proportional hazard regression models to assess factors affecting outcomes. RESULTS: The median follow-up duration was 25.8 months. Baseline clinical characteristics were similar between groups. There were no significant differences between the two groups in the rate of clinical remission or clinical response at 8 or 52 weeks. Multivariate analyses also showed that long-term outcomes were not significantly different (adjusted hazard ratio [HR], 1.45; 95% confidence interval [CI], 0.81 to 2.56; p=0.208). An elevated C-reactive protein level (greater than 5 mg/L) was a significant predictive factor for poor outcomes (adjusted HR, 2.25; 95% CI, 1.37 to 3.70; p=0.001). During the follow-up period, the rates of adverse event were not significantly different between the two groups (p=0.441). CONCLUSIONS: In our study, infliximab and adalimumab had similar treatment efficacy and longterm outcomes in biologic-naïve patients with moderate to severe UC.
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Adalimumab/uso terapéutico , Colitis Ulcerosa , Infliximab/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Productos Biológicos , Colitis Ulcerosa/tratamiento farmacológico , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: Wnt and mammalian target of rapamycin (mTOR) are major molecular signaling pathways associated with the development and progression of tumor, as well as the maintenance and proliferation of cancer stem cells (CSCs), in colorectal cancer (CRC). Identifying patients at risk of poor prognosis is important to determining whether to add adjuvant treatment in stage II CRC and thus improve survival. In the present study, we evaluated the prognostic value of Wnt, mTOR, and CSC markers as survival predictors in stage II CRC. MATERIALS AND METHODS: We identified 148 cases of stage II CRC and acquired their tumor tissue. Tissue microarrays for immunohistochemical staining were constructed, and the expressions of CD166, CD44, EphB2, ß-catenin, pS6 were evaluated using immunohistochemical staining. RESULTS: The expressions of CD166 (p=0.045) and pS6 (p=0.045) and co-expression of pS6/CD166 (p=0.005), pS6/CD44 (p=0.042), and pS6/CD44/CD166 (p=0.013) were negatively correlated with cancer-specific survival. Cox proportional hazard analysis showed the combination of CD166/pS6 [hazard ratio, 9.42; 95% confidence interval, 2.36-37.59; p=0.002] to be the most significant predictor related with decreased cancer-specific survival. In addition, co-expression of CD44/CD166 (p=0.017), CD166/ß-catenin (p=0.036), CD44/ß-catenin (p=0.001), and CD44/CD166/ß-catenin (p=0.001) were significant factors associated with liver metastasis. CONCLUSION: Specific combinations of CSC markers and ß-catenin/mTOR signaling could be a significant predictor of poor survival in stage II CRC.
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Antígenos CD/metabolismo , Biomarcadores de Tumor/análisis , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Serina-Treonina Quinasas TOR/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias del Colon/metabolismo , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Neoplasias Colorrectales/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Receptores de Hialuranos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/trasplante , Pronóstico , Transducción de Señal , Serina-Treonina Quinasas TOR/análisis , beta CateninaRESUMEN
PURPOSE OF REVIEW: The treatment of intestinal Behcet's disease (BD) is challenging, and one-third of patients require surgery due to failure of conventional therapies. Anti-tumor necrosis factor-α (TNF-α) and other new biologics have been actively investigated for managing intestinal BD. In this article, we review the updated experiences and up-to-date clinical data on anti-TNF-α and other biologics for the management of intestinal BD. RECENT FINDINGS: Recent prospective studies have proved the efficacy and safety of infliximab and adalimumab for treating intestinal BD. Recent studies with other biologics such as anti-interleukin (IL)-1 (anakinra and canakinumab) and anti-IL-6 (tocilizumab) have shown promising results in patients with systemic, including intestinal, BD. Both infliximab and adalimumab can be useful in managing patients with intestinal BD, especially severe or refractory cases, with a similar efficacy and safety profile. More evidence for anakinra, canakinumab, tocilizumab, anti-IL-17 (secukinumab), and anti-IL-12/23 (ustekinumab) in intestinal BD is required.
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Síndrome de Behçet/tratamiento farmacológico , Factores Biológicos/uso terapéutico , Intestino Delgado , HumanosRESUMEN
BACKGROUND & AIMS: Thiopurine-related myelosuppression (most frequently leukopenia) interferes with thiopurine therapy for patients with inflammatory bowel diseases (IBD). We investigated whether pretreatment analyses genetic variants associated with thiopurine-induced leukopenia could be used to effectively identify patients who required dose adjustments. METHODS: We performed a multicenter, prospective study of patients with IBD at 5 tertiary medical centers in Korea, from January 2016 through September 2018. Seventy-two patients were randomly assigned to a group that underwent genotype analysis for the NUDT15 variant (rs116855232) and FTO variant (rs79206939) and 3 common TPMT variants (rs1800460, rs1800462, rs1142345) associated with myelosuppression and 92 patients were assigned to a group that did not undergo genotype analysis (non-genotyping group). Patients heterozygous for any variant received 50 mg azathioprine equivalents, whereas those who were homozygous for any variant received alternative drugs. Patients who did not carry any of the genetic variants and patients in the non-genotyping group received 50 mg azathioprine equivalents followed by dose escalation up to 2-2.5 mg/kg. Myelosuppression was defined as white blood cell counts below 3000/µL, levels of hemoglobin 10 g/dL, or platelet counts below 100 K/µL. RESULTS: Twelve patients (16.7%) in the genotype analysis group and 33 patients (35.9%) in the non-genotyping group developed myelosuppression (P=.005). A multivariate analysis revealed that body mass indices above 21 kg/m2 (hazard ratio [HR], 0.43; 95% CI, 0.22-0.81; P = .009), pretreatment genotype analysis (HR, 0.37; 95% CI, 0.18-0.77; P = .008), and the maximum dose of thiopurines (HR, 0.34; 95% CI, 0.19-0.59; P < .001) independently decreased risk of myelosuppression. Pretreatment genotype analysis reduced numbers of outpatient clinic visit and numbers of patients with drug discontinuation or dose reductions. CONCLUSIONS: In a randomized controlled study of patients undergoing thiopurine therapy for IBD, we found that selection of therapy based on genetic variants associated with thiopurine-induced leukopenia significantly reduced the proportion of patients with myelosuppression during treatment. ClinicalTrials.gov no: NCT03719118.
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Enfermedades Inflamatorias del Intestino , Metiltransferasas , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Azatioprina/efectos adversos , Genotipo , Humanos , Incidencia , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Mercaptopurina/efectos adversos , Metiltransferasas/genética , Estudios ProspectivosRESUMEN
BACKGROUND/AIMS: Patients with inflammatory bowel disease (IBD) are usually hospitalized because of aggravated gastrointestinal symptoms. Many clinicians empirically advise these patients to fast once they are admitted. However, there has been no evidence that maintaining a complete bowel rest improves the disease course. Therefore, we aimed to investigate the effects of fasting on disease course in admitted patients with IBD or intestinal Behçet's disease. METHODS: A total of 222 patients with IBD or intestinal Behçet's disease, who were admitted for disease-related symptoms, were retrospectively analyzed. We divided them into 2 groups: fasting group (allowed to take sips of water but no food at the time of admission) and dietary group (received liquid, soft, or general diet). RESULTS: On admission, 124 patients (55.9%) started fasting and 98 patients (44.1%) started diet immediately. Among patients hospitalized through the emergency room, a significantly higher proportion underwent fasting (63.7% vs. 21.4%, P<0.001); however, 96.0% of the patients experienced dietary changes. Corticosteroid use (P<0.001; hazard ratio, 2.445; 95% confidence interval, 1.506-3.969) was significantly associated with a reduction in the disease activity score, although there was no significant difference between the fasting group and the dietary group in disease activity reduction (P=0.111) on multivariate analysis. CONCLUSIONS: In terms of disease activity reduction, there was no significant difference between the fasting and dietary groups in admitted patients with IBD, suggesting that imprudent fasting is not helpful in improving the disease course. Therefore, peroral diet should not be avoided unless not tolerated by the patient.