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BACKGROUND AND AIM: Although diet is one of the potential environmental factors affecting ulcerative colitis (UC), evidence is not sufficient to draw definitive conclusions. This Japanese case-control study examined the association between the consumption of coffee, other caffeine-containing beverages and food, and total caffeine and the risk of UC. METHODS: The study involved 384 UC cases and 665 control subjects. Intake of coffee, decaffeinated coffee, black tea, green tea, oolong tea, carbonated soft drinks, and chocolate snacks was measured with a semiquantitative food-frequency questionnaire. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, body mass index, and intake of vitamin C, retinol, and total energy. RESULTS: Higher consumption of coffee and carbonated soft drinks was associated with a reduced risk of UC with a significant dose-response relationship (P for trend for coffee and carbonated soft drinks were <0.0001 and 0.01, respectively), whereas higher consumption of chocolate snacks was significantly associated with an increased risk of UC. No association was observed between consumption of decaffeinated coffee, black tea, green tea, or oolong tea and the risk of UC. Total caffeine intake was inversely associated with the risk of UC; the adjusted odds ratio between extreme quartiles was 0.44 (95% confidence interval: 0.29-0.67; P for trend <0.0001). CONCLUSIONS: We confirmed that intake of coffee and caffeine is also associated with a reduced risk of UC in Japan where people consume relatively low quantities of coffee compared with Western countries.
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Café , Colitis Ulcerosa , Humanos , Cafeína/efectos adversos , Cafeína/análisis , Japón/epidemiología , Estudios de Casos y Controles , Colitis Ulcerosa/epidemiología , Colitis Ulcerosa/etiología , Colitis Ulcerosa/prevención & control , Factores de Riesgo , Té/efectos adversosRESUMEN
BACKGROUND: The interleukin (IL)-23/Th17 pathway plays a critical role in ulcerative colitis (UC). The IL-12p40 subunit, which is shared by IL-23 and IL-12, is encoded by the IL12B gene. The current case-control study investigated the association between IL12B SNP rs6887695 and the UC risk. METHODS: There were 384 cases within 4 years of UC diagnosis and 661 controls who were enrolled. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, and body mass index. RESULTS: Subjects with the GG IL12B SNP rs6887695 genotype had a significantly increased risk of UC compared with those with the CC genotype (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.08-2.36). This positive association was also significant using the additive and recessive models (AOR, 1.25; 95% CI, 1.03-1.52; AOR, 1.50; 95% CI, 1.08-2.09, respectively). An independent inverse relationship was observed between ever alcohol consumption and the UC risk in those with the CC genotype while no significant association was found in those with at least one G allele (P for interaction = 0.0008). CONCLUSIONS: IL12B SNP rs6887695 was significantly associated with UC. The influence of alcohol consumption might rely on rs6887695.
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Colitis Ulcerosa , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/genética , Estudios de Casos y Controles , Colitis Ulcerosa/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Subunidad p40 de la Interleucina-12/genética , Japón , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
BACKGROUND: Acute esophageal necrosis (AEN), commonly referred to as Gurvits syndrome or "black esophagus", is a rare clinical disease. We present a case of AEN associated with diabetic ketoacidosis (DKA). CASE PRESENTATION: A 66-year-old male came to our hospital with coffee-ground emesis, dyspnea, and general malaise. He was treated for type 2 diabetes mellitus using insulin and had not been taking his medication, including insulin, for several days. Laboratory analysis revealed severe hyperglycemia (730 mg/dL), normocytic anemia (hemoglobin level, 7.7 g/dL; mean corpuscular volume, 100.4 fL), high serum potassium (7.6 mEq/L), and a high level of blood urea (98.7 mg/dL). Ketones and glucose were detected in the urine, and serum ß-hydroxybutyrate was elevated (2132 µmol/L). Arterial blood gas analysis confirmed metabolic acidosis (pH, 7.29; HCO3, 10.5 mmol/L). Collectively, the patient was diagnosed with DKA and upper gastrointestinal bleeding. The patient's condition improved with intravenous fluids, and he received intravenous insulin to treat DKA. According to these findings, the patient was diagnosed with DKA and upper gastrointestinal bleeding. The patient underwent esophagogastroduodenoscopy (EGD) which revealed a circumferential necrosis of the middle and distal esophagus, immediately proximal to the gastroesophageal junction. The patient was then treated with an intravenous proton pump inhibitor. The patient continued to improve with conservative treatment and was subsequently discharged in a stable condition. An EGD repeated 14 days after discharge showed complete healing of the necrotic-like mucosal change without stricture formation of the esophagus. CONCLUSIONS: AEN is rare but potentially life-threatening case of upper gastrointestinal bleeding. Therefore, a clinician should be aware of AEN as a potential cause of upper gastrointestinal bleeding in elderly patients with poorly controlled diabetes and significant comorbidities.
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Diabetes Mellitus Tipo 2 , Cetoacidosis Diabética , Enfermedades del Esófago , Insulinas , Enfermedad Aguda , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Cetoacidosis Diabética/complicaciones , Enfermedades del Esófago/complicaciones , Hemorragia Gastrointestinal/complicaciones , Humanos , Masculino , Necrosis , SíndromeRESUMEN
BACKGROUND AND AIM: Although an inverse relationship between current smoking and the development of ulcerative colitis (UC) has been shown in North America and Europe, evidence is limited in Asian countries, where the incidence of UC is rapidly increasing. This Japanese case-control study examined the association between active and passive smoking and risk of UC. METHODS: A self-administered questionnaire was used to obtain information on smoking and potential confounding factors in 384 cases with a diagnosis of UC within the past 4 years and 665 controls. RESULTS: Compared with having never smoked, having ever smoked was associated with an increased risk of UC (adjusted odds ratio [OR] = 1.70, 95% confidence interval [CI]: 1.23-2.37). No association was observed between current smoking and risk of UC, but former smokers had a significant elevation in risk (adjusted OR = 2.40, 95% CI: 1.67-3.45). There was a positive dose-response relationship with pack-years smoked (P for trend = 0.006). Among never smokers, passive smoking exposure at home was significantly associated with an increased risk of UC (adjusted OR = 1.90, 95% CI: 1.30-2.79). A significant dose-response gradient was also observed between pack-years of passive smoking at home and risk of UC (P for trend = 0.0003). CONCLUSIONS: We confirmed that former smoking elevated the risk of UC, whereas an inverse association between current smoking and the risk of UC did not reach a statistically significant level. Passive smoking may be associated with an increased risk of UC.
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Colitis Ulcerosa , Contaminación por Humo de Tabaco , Estudios de Casos y Controles , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/epidemiología , Colitis Ulcerosa/etiología , Humanos , Japón/epidemiología , Factores de Riesgo , Contaminación por Humo de Tabaco/efectos adversosRESUMEN
We report a case of a 15-year-old girl who developed refractory Clostridioides difficile infection (CDI) after allogeneic bone marrow transplantation (BMT). She was treated successfully with fecal microbiota transplantation (FMT). The patient who had aplastic anemia underwent allogeneic BMT from an HLA 1-locus-mismatched unrelated donor. Four months later, she developed gastrointestinal graft-versus-host disease (GVHD), and immunosuppressive treatment improved the GVHD. However, she developed CDI 5 months after BMT and experienced recurrence after that. Fifteen months after transplant, CDI relapsed despite discontinuation of immunosuppressive treatment; thus, she underwent FMT. Colonoscopy at the time of FMT revealed round aphthae, mainly in the ileocecum, and colonic biopsy revealed inflammatory cell infiltration and noncaseating epithelioid granuloma, which fulfilled the diagnostic criteria for Crohn's disease. Following FMT for CDI, she was treated with enteric budesonide and intravenous methotrexate for Crohn's disease. These interventions resulted in a marked improvement in both CDI and Crohn's disease. Twenty-eight months after FMT, both CDI and Crohn's disease remained in remission with oral mesalamine monotherapy.
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Clostridioides difficile , Infecciones por Clostridium , Enfermedad de Crohn , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Adolescente , Médula Ósea , Trasplante de Médula Ósea , Infecciones por Clostridium/terapia , Trasplante de Microbiota Fecal/métodos , Femenino , Humanos , Recurrencia , Receptores de Trasplantes , Resultado del TratamientoRESUMEN
Objective In patients with ulcerative colitis (UC), the relationship between the initial endoscopic findings and the response to anti-tumor necrosis factor (TNF)-α antibodies remains unclear. We herein evaluated the potential of endoscopic assessment using the ulcerative colitis endoscopic index of severity (UCEIS) to predict the response to anti-TNF-α antibodies. Methods We enrolled 64 patients with UC undergoing anti-TNF-α maintenance therapy with infliximab (IFX) or adalimumab (ADA) between April 2010 and March 2015. Anti-TNF-α trough levels were determined by ELISA. Endoscopic disease activity was assessed using the UCEIS. Results The clinical response rate at 8 weeks was 77.4% for IFX and 66.7% for ADA. Serum albumin levels were significantly higher and the UCEIS bleeding descriptor before treatment was significantly lower in the responders than in the non-responders (p < 0.05 each). The CRP levels at 2 weeks were significantly lower in the responders (p < 0.001). The serum albumin levels before treatment were significantly higher and the UCEIS erosions and ulcers descriptor was significantly lower in the mucosal healing group than in the non-mucosal healing group (p < 0.05 each). A significant and negative correlation between the trough levels of anti-TNF-α antibodies and the UCEIS descriptors was observed. The trough levels of anti-TNF-α antibodies to achieve mucosal healing were 2.7 µg/mL for IFX and 10.3 µg/mL for ADA. Conclusions The UCEIS score, as well as some clinical markers (serum albumin and CRP levels), is useful for the prediction of the treatment outcome of UC patients in response to anti-TNF-α antibodies.
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Anticuerpos Monoclonales/uso terapéutico , Colitis Ulcerosa/patología , Colitis Ulcerosa/terapia , Factor de Necrosis Tumoral alfa/inmunología , Adalimumab/uso terapéutico , Anticuerpos Monoclonales/análisis , Endoscopía , Predicción , Humanos , Infliximab/uso terapéuticoRESUMEN
Mannan (mannose)-binding protein (MBP) is a C-type serum lectin that plays a key role in innate immunity. MBP forms large multimers (200-600 kDa) and exhibits broad specificity for mannose, N-acetylglucosamine, and fucose. MBP exhibits high affinity for unique oligosaccharides that have been isolated from human colorectal carcinoma (SW1116) cells and characterized as highly fucosylated high m.w. type 1 Lewis glycans. In this study, we first demonstrated that MBP recognizes human primary colorectal carcinoma tissues through tumor-associated MBP ligands. We performed fluorescence-based histochemistry of MBP in human colorectal carcinoma tissues and showed that MBP clearly stained cancer mucosae in a Ca(2+)-dependent manner. Coincubation with plant (Aleuria aurantia) lectin, but not Con A, blocked MBP staining, indicating that fucose, rather than mannose, is involved in this interaction. The expression of MBP ligands was detected in 127 of 330 patients (38.5%), whereas, most significantly, there was no expression in 69 nonmalignant tissues. The MBP-staining pattern in cancer mucosae significantly overlapped with that of Lewis b [Fucα1-2Galß1-3(Fucα1-4)GlcNAc] staining, but the Lewis b staining in normal tissues was not associated with MBP staining. In addition, the MBP staining correlated inversely with the expression of CA19-9 Ag, and MBP stained 11 of 25 (44%) CA19-9 (sialyl Lewis a [NeuAc(α2-3)Galß1-3(Fucα1-4)GlcNAc])(-) colorectal carcinoma tissues. We found a favorable prognosis in patients with MBP ligand(+) tumors. These results suggest that selective recognition of cancer cells by endogenous MBP seems to be associated with an antitumor effect and that tissue staining with MBP in combination with CA19-9 may serve as a novel indicator of colorectal carcinoma tissues.
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Adenocarcinoma Mucinoso/química , Adenocarcinoma/química , Antígenos de Neoplasias/análisis , Neoplasias Colorrectales/química , Lectina de Unión a Manosa/fisiología , Oligosacáridos/análisis , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidad , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Antígeno CA-19-9/análisis , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/mortalidad , Epitelio/química , Técnica del Anticuerpo Fluorescente Indirecta , Antígenos HLA-DR/análisis , Humanos , Mucosa Intestinal/química , Antígenos del Grupo Sanguíneo de Lewis , Ligandos , Linfocitos Infiltrantes de Tumor/química , Persona de Mediana Edad , Metástasis de la Neoplasia , Valor Predictivo de las Pruebas , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND AND AIMS: The serum trough level of adalimumab (ADA) associated with mucosal healing (MH) remains unclear. Our objective was to determine the association between ADA trough levels and the endoscopic activity in Crohn's disease. MATERIALS AND METHODS: This was a cross-sectional study including 42 patients with Crohn's disease. Endoscopic activity was assessed using the modified Rutgeerts scoring system. The primary outcome was mucosal healing, and the secondary outcomes were serum levels of C-reactive protein and albumin. RESULTS: Endoscopic disease activity negatively correlated with serum ADA trough levels (Spearman's rank correlation coefficient (ρ) = -0.42, P < 0.01). MH was achieved in 14 of 42 patients (33.3%). Serum ADA trough levels were significantly higher in the MH group than in the no-MH group (ADA mean trough level, 11.7 vs 7.5 µg/mL). The proportion of patients with ADA as the first biologic was significantly higher in the MH group than in the no-MH group (85.7% vs 53.5%, P = 0.04). The ADA trough levels that were best associated with normal C-reactive protein and albumin levels were 5.57 µg/mL (odds ratio [OR] 16.0, specificity 0.80) and 6.95 µg/mL (OR 9.2, specificity 0.81), respectively. The ADA trough level that was best associated with MH was 7.9 µg/mL (OR 13.5, specificity 0.86). The endoscopic disease activity was significantly higher in the patients with ADA as the second biologic as compared with those with ADA as the first biologic (P < 0.05). CONCLUSION: Mucosal healing requires higher ADA trough levels, compared with those required to normalization of routine clinical markers.
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Adalimumab/sangre , Enfermedad de Crohn/sangre , Fármacos Gastrointestinales/sangre , Adalimumab/uso terapéutico , Adulto , Proteína C-Reactiva/análisis , Colonoscopía , Enfermedad de Crohn/tratamiento farmacológico , Estudios Transversales , Femenino , Fármacos Gastrointestinales/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Albúmina Sérica/análisis , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Cicatrización de Heridas/efectos de los fármacos , Adulto JovenRESUMEN
BACKGROUND: The global alteration of the gut microbial community (dysbiosis) plays an important role in the pathogenesis of inflammatory bowel diseases (IBDs). However, bacterial species that characterize dysbiosis in IBD remain unclear. In this study, we assessed the alteration of the fecal microbiota profile in patients with Crohn's disease (CD) using 16S rRNA sequencing. SUMMARY: Fecal samples from 10 inactive CD patients and 10 healthy individuals were subjected to 16S rRNA sequencing. The V3-V4 hypervariable regions of 16S rRNA were sequenced by the Illumina MiSeq™II system. The average of 62,201 reads per CD sample was significantly lower than the average of 73,716 reads per control sample. The genera Bacteroides, Eubacterium, Faecalibacterium and Ruminococcus significantly decreased in CD patients as compared to healthy controls. In contrast, the genera Actinomyces and Bifidobacterium significantly increased in CD patients. At the species level, butyrate-producing bacterial species, such as Blautia faecis, Roseburia inulinivorans, Ruminococcus torques, Clostridium lavalense, Bacteroides uniformis and Faecalibacterium prausnitzii were significantly reduced in CD patients as compared to healthy individuals (p < 0.05). These results of 16S rRNA sequencing were confirmed in additional CD patients (n = 68) and in healthy controls (n = 46) using quantitative PCR. The abundance of Roseburia inulinivorans and Ruminococcus torques was significantly lower in C-reactive protein (CRP)-positive CD patients as compared to CRP-negative CD patients (p < 0.05). KEY MESSAGE: The dysbiosis of CD patients is characterized by reduced abundance of multiple butyrate-producing bacteria species.
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Enfermedad de Crohn/microbiología , Disbiosis/microbiología , Microbioma Gastrointestinal/genética , Actinomyces/genética , Actinomyces/metabolismo , Adulto , Bacteroides/genética , Bacteroides/metabolismo , Bifidobacterium/genética , Bifidobacterium/metabolismo , Butiratos/metabolismo , Estudios de Casos y Controles , Clostridium/genética , Clostridium/metabolismo , Enfermedad de Crohn/metabolismo , ADN Bacteriano/genética , ADN Ribosómico/genética , Disbiosis/metabolismo , Eubacterium/genética , Eubacterium/metabolismo , Heces/microbiología , Femenino , Microbioma Gastrointestinal/fisiología , Humanos , Masculino , ARN Ribosómico 16S/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Ruminococcus/genética , Ruminococcus/metabolismo , Análisis de Secuencia de ADN , Análisis de Secuencia de ARNRESUMEN
Altered gut microbial ecology contributes to the development of metabolic diseases including obesity. In this study, we performed 16S rRNA sequence analysis of the gut microbiota profiles of obese and lean Japanese populations. The V3-V4 hypervariable regions of 16S rRNA of fecal samples from 10 obese and 10 lean volunteers were sequenced using the Illumina MiSeq(TM)II system. The average body mass index of the obese and lean group were 38.1 and 16.6 kg/m(2), respectively (p<0.01). The Shannon diversity index was significantly higher in the lean group than in the obese group (p<0.01). The phyla Firmicutes and Fusobacteria were significantly more abundant in obese people than in lean people. The abundance of the phylum Bacteroidetes and the Bacteroidetes/Firmicutes ratio were not different between the obese and lean groups. The genera Alistipes, Anaerococcus, Corpococcus, Fusobacterium and Parvimonas increased significantly in obese people, and the genera Bacteroides, Desulfovibrio, Faecalibacterium, Lachnoanaerobaculum and Olsenella increased significantly in lean people. Bacteria species possessing anti-inflammatory properties, such as Faecalibacterium prausnitzii, increased significantly in lean people, but bacteria species possessing pro-inflammatory properties increased in obese people. Obesity-associated gut microbiota in the Japanese population was different from that in Western people.
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BACKGROUND AND AIM: Acute pancreatitis following balloon-assisted enteroscopy is a rare but serious complication. The causative mechanism is uncertain and prevention strategies are not established. We conducted a retrospective study to clarify the risk factors for pancreatic hyperamylasemia. METHODS: Eighty-four patients undergoing peroral single-balloon enteroscopy (SBE) were enrolled in this study. Serum pancreatic and salivary amylase levels were measured 2 h after endoscopic examination. RESULTS: We experienced three patients with post-SBE pancreatitis. Factors predicting pancreatic hyperamylasemia were: (i) elderly patients; (ii) deeper insertion; and (iii) clockwise insertion. In contrast, younger age at examination was a significant factor observed in salivary hyperamylasemia. CONCLUSIONS: It is important to measure pancreatic amylase and not total amylase after SBE. When carrying out peroral SBE, the distance of insertion should be reduced especially if the scope traces a clockwise loop or the subject is elderly.
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Endoscopios Gastrointestinales , Endoscopía Gastrointestinal/efectos adversos , Hiperamilasemia/complicaciones , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Pancreatitis/etiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Amilasas/sangre , Análisis de Varianza , Estudios de Cohortes , Endoscopía Gastrointestinal/métodos , Femenino , Estudios de Seguimiento , Humanos , Hiperamilasemia/diagnóstico , Masculino , Persona de Mediana Edad , Cirugía Endoscópica por Orificios Naturales/métodos , Pancreatitis/fisiopatología , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Estadísticas no Paramétricas , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
Metastasis to the skeletal muscle from gastric cancer is relatively rare. We report cases of 3 patients undergoing chemotherapy for gastric cancer with metastasis to the skeletal muscle. Case 1: A man in his 70s was diagnosed with advanced gastric cancer (cT4N3M1P0, stage IV), with metastasis to the lung, brain, lymph node, and iliopsoas muscle. Case 2: A man in his 60s was diagnosed with advanced gastric cancer (cT3N3M1P0, stage IV), with metastasis to the brain, lung, lymph node, and iliopsoas muscle. Case 3: A man in his 50s was diagnosed with advanced gastric cancer (cT4N3M1P0, stage IV), with metastasis to the urinary duct, lymph node, back muscle, and iliopsoas muscle. All 3 patients died within 7-8 months after the diagnosis due to progressive disease despite chemotherapy. The prognosis of these 3 patients was significantly poorer than that of patients in our hospital with metastasis not involving the skeletal muscle (p<0.01). Accordingly, metastasis to the skeletal muscle may be an adverse prognostic factor in gastric cancer.
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Enfermedades Musculoesqueléticas/patología , Neoplasias Gástricas/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado Fatal , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Musculoesqueléticas/etiología , Estadificación de Neoplasias , Cuidados Paliativos , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/terapiaRESUMEN
OBJECTIVE: Intestinal fibrosis is a clinically important issue in Crohn's disease (CD). Heat shock protein (HSP) 47 is a collagen-specific molecular chaperone involved in fibrotic diseases. The molecular mechanisms of HSP47 induction in intestinal fibrosis related to CD, however, remain unclear. Here we investigated the role of interleukin (IL)-17A-induced HSP47 expression in intestinal fibrosis in CD. DESIGN: Expressions of HSP47 and IL-17A in the intestinal tissues of patients with IBD were determined. HSP47 and collagen I expressions were assessed in intestinal subepithelial myofibroblasts (ISEMFs) isolated from patients with IBD and CCD-18Co cells treated with IL-17A. We examined the role of HSP47 in IL-17A-induced collagen I expression by administration of short hairpin RNA (shRNA) to HSP47 and investigated signalling pathways of IL-17A-induced HSP47 expression using specific inhibitors in CCD-18Co cells. RESULTS: Gene expressions of HSP47 and IL-17A were significantly elevated in the intestinal tissues of patients with active CD. Immunohistochemistry revealed HSP47 was expressed in α-smooth muscle actin (α-SMA)-positive cells and the number of HSP47-positive cells was significantly increased in the intestinal tissues of patients with active CD. IL-17A enhanced HSP47 and collagen I expressions in ISEMFs and CCD-18Co cells. Knockdown of HSP47 in these cells resulted in the inhibition of IL-17A-induced collagen I expression, and analysis of IL-17A signalling pathways revealed the involvement of c-Jun N-terminal kinase in IL-17A-induced HSP47 expression. CONCLUSIONS: IL-17A-induced HSP47 expression is involved in collagen I expression in ISEMFs, which might contribute to intestinal fibrosis in CD.
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Colágeno Tipo I/metabolismo , Enfermedad de Crohn , Fibrosis/metabolismo , Proteínas del Choque Térmico HSP47/metabolismo , Interleucina-17/metabolismo , Mucosa Intestinal , Intestinos , Adulto , Anciano , Enfermedad de Crohn/metabolismo , Enfermedad de Crohn/patología , Femenino , Perfilación de la Expresión Génica , Humanos , Mucosa Intestinal/metabolismo , Intestinos/patología , Masculino , Miofibroblastos/metabolismo , Miofibroblastos/patologíaRESUMEN
BACKGROUND/AIMS: Only a few reports have examined the relationship between balloon-assisted enteroscopy (BAE)-based mucosal lesion severity in Crohn's disease (CD) using clinical variables such as serum levels of disease activity markers and Crohn's Disease Activity Index. We analysed whether clinical variables are useful for predicting mucosal healing (MH) in various CD types. METHODOLOGY: A total of 173 CD patients who underwent BAE were enrolled. Endoscopic findings were assessed using the modified Rutgeerts score (MRS). In this study, all observed samples of intestine, small bowel and large bowel were individually scored. The 'ileum group' included patients with MRS ileum scores greater than or equal to MRS colon scores (n = 139), whereas the 'colon group' included patients who had colon scores greater than or equal to MRS ileum scores (n = 56). RESULTS: Spearman's rank correlation between MRS and practical clinical parameters was stronger in the colon group than in the ileum group. Receiver operating characteristic analysis revealed that the colon group had better correlativity for MH prediction than the ileum group. The MH index using C-reactive protein and serum albumin obtained from logistic regression analysis improved the accuracy of MH prediction by 74.3%. CONCLUSION: A combination of serum albumin and C-reactive protein is useful for MH prediction. However, the reliability of MH prediction can differ depending on the dominant area of the mucosal lesions.
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Colon/patología , Enfermedad de Crohn/diagnóstico , Íleon/patología , Mucosa Intestinal/patología , Cicatrización de Heridas , Adolescente , Adulto , Anciano , Área Bajo la Curva , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Enfermedad de Crohn/sangre , Enfermedad de Crohn/patología , Endoscopía Gastrointestinal , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC , Albúmina Sérica/análisis , Albúmina Sérica Humana , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND: The imbalance of commensal bacteria is called dysbiosis in intestinal microflora. Secreted IgA in the intestinal lumen plays an important role in the regulation of microbiota. Although dysbiosis of gut bacteria is reported in IBD patients, it remains unclear what makes dysbiosis of their microflora. The intervention method for remedy of dysbiosis in IBD patients is not well established. In this study, we focused on the quality of human endogenous IgA and investigated whether mouse monoclonal IgA which binds to selectively colitogenic bacteria can modulate human gut microbiota with IBD patients. METHODS: IgA-bound and -unbound bacteria were sorted by MACS and cell sorter. Sorted bacteria were analyzed by 16S rRNA sequencing to investigate what kinds of bacteria endogenous IgA or mouse IgA recognized in human gut microbiota. To evaluate the effect of mouse IgA, gnotobiotic mice with IBD patient microbiota were orally administrated with mouse IgA and analyzed gut microbiota. RESULTS: We show that human endogenous IgA has abnormal binding activity to gut bacteria in IBD patients. Mouse IgA can bind to human microbiota and bind to selectively colitogenic bacteria. The rW27, especially, has a growth inhibitory activity to human colitogenic bacteria. Furthermore, oral administration of mouse IgA reduced an inflammation biomarker, fecal lipocalin 2, in mice colonized with IBD patient-derived microbiota, and improved dysbiosis of IBD patient sample. CONCLUSION: Oral treatment of mouse IgA can treat gut dysbiosis in IBD patients by modulating gut microbiota.
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BACKGROUND AND AIMS: Dysbiosis is thought to be relevant to the etiology and pathogenesis of Crohn's disease (CD). In this study, we investigated the abundance of Faecalibacterium prausnitzii, as well as Bilophila wadsworthia, in the gut microbiota of Japanese CD patients. METHODS: Forty-seven CD patients and 20 healthy controls were enrolled. Abundance of F. prausnitzii in fecal samples was quantified by real-time polymerase chain reaction. The gut microbiota profile was evaluated by terminal restriction fragment length polymorphisms. RESULTS: The abundance of F. prausnitzii significantly decreased in CD patients compared with healthy subjects. B. wadsworthia was scarcely detected in the same samples. Among CD patients, the Crohn's Disease Activity Index, C-reactive protein levels, and erythrocyte sedimentation rate were significantly lower, and serum albumin levels were significantly higher in the high F. prausnitzii group compared with the low group. Terminal restriction fragment length polymorphisms analysis showed that fecal bacterial communities of CD patients differed from those of healthy individuals. The changes in simulated bacterial composition indicated that class Clostridia, including genus Faecalibacterium, was significantly less abundant in CD patients as compared with healthy individuals. The bacterial diversity measured by the Shannon Diversity Index was significantly reduced in CD patients compared with healthy individuals. CONCLUSION: The decreased abundance of class Clostridia, including F. prausnitzii, may translate into a reduction of commensal bacteria-mediated, anti-inflammatory activities in the mucosa, which are relevant to the pathophysiology of CD. In contrast, the role of B. wadsworthia was suspected to be minimal.
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Bilophila/aislamiento & purificación , Clostridium/fisiología , Enfermedad de Crohn/microbiología , Tracto Gastrointestinal/microbiología , Metagenoma , Adulto , Estudios de Casos y Controles , Cartilla de ADN/química , ADN Bacteriano/análisis , Heces/microbiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Longitud del Fragmento de Restricción , Reacción en Cadena en Tiempo Real de la Polimerasa , Índice de Severidad de la EnfermedadRESUMEN
The complement system is a potent effector of innate immunity. To elucidate the pathophysiological role of the complement system in inflammatory bowel disease, we evaluated the effects of anti-C5 antibodies on the development of dextran sulfate sodium-induced colitis in mice. Dextran sulfate sodium-colitis was induced in BALB/c mice with intraperitoneal administrations of anti-C5 antibodies (1 mg/body [DOSAGE ERROR CORRECTED]) every 48 h. Tissue samples were evaluated by standard histological procedures. The mucosal mRNA expression of the inflammatory cytokines was analyzed by real-time PCR. Body weight loss in the mice was completely blocked by the administration of anti-C5 antibody. The disease activity index was significantly lower in the anti-C5 antibody-treated mice than the dextran sulfate sodium mice. The colonic weight/length ratio, histological colitis score and mucosal myeloperoxidase activity were significantly lower in the anti-C5 antibody-treated mice than the dextran sodium sulfate mice. The administration of the anti-C5 antibody significantly reduced the mucosal expression of mRNAs for tumor necrosis factor-α, interleukin-1ß and interleukin-6. In conclusion, the complement system plays a role in the development of dextran sodium sulfate-induced experimental colitis.
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A 33-year-old woman with Crohn disease complained of diarrhea and hematochezia from the fifth week of her third pregnancy and was hospitalized. Because her CDAI indicated 307.1 points and colonoscopy showed multiple longitudinal ulcers in the distal colon, adalimumab therapy was initiated. The CDAI had decreased to 160.0 points and the colonic ulcers improved by 22 days after beginning the administration of adalimumab. Although adalimumab therapy was continued every 2 weeks during the third trimester, fetus growth was not affected and the woman delivered a healthy child. Adalimumab should be considered as one treatment for Crohn disease during pregnancy.
Asunto(s)
Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Complicaciones del Embarazo/tratamiento farmacológico , Adalimumab , Adulto , Estudios de Factibilidad , Femenino , Humanos , EmbarazoRESUMEN
Objectives: Self-expandable metal stents are widely used for the treatment of malignant colorectal stenosis (MCS). In elderly individuals with MCS, self-expandable metal stents are often used as a palliative treatment, but prophylactic stent placement is not recommended. We investigated the efficacy and safety of self-expandable metal stents for the elderly in a palliative setting, specifically in a prophylactic setting. Methods: Elderly patients with MCS who received a palliative stent (the stent group) or palliative stoma (the stoma group) were retrospectively enrolled between April 2017 and June 2022, and the prognosis and complication rates were assessed. Additionally, patients in the stent group were divided into symptomatic and asymptomatic subgroups, and prognosis, stent patency, and complication rates were evaluated. Results: During the study period, 31 patients with a mean age of 85.4 years and 12 patients with a mean age of 82.0 years were enrolled in the stent and stoma groups, respectively. While overall survival and complication rates were comparable, the length of hospital stay was significantly shorter in the stent group. Of the 31 patients in the stent group, 16 asymptomatic patients received prophylactic stenting, which was not associated with increased complication rates. Conclusions: Palliative stents for MCS appear to be effective and safe even in the elderly, and thus, prophylactic stents can be considered for asymptomatic patients.
RESUMEN
Dendritic cell (DC)-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is a type II transmembrane C-type lectin expressed on DCs such as myeloid DCs and monocyte-derived DCs (MoDCs). Recently, we have reported that DC-SIGN interacts with carcinoembryonic antigen (CEA) expressed on colorectal carcinoma cells. CEA is one of the most widely used tumor markers for gastrointestinal cancers such as colorectal cancer. On the other hand, other groups have reported that the level of Mac-2-binding protein (Mac-2BP) increases in patients with pancreatic, breast, and lung cancers, virus infections such as human immunodeficiency virus and hepatitis C virus, and autoimmune diseases. Here, we first identified Mac-2BP expressed on several colorectal carcinoma cell lines as a novel DC-SIGN ligand through affinity chromatography and mass spectrometry. Interestingly, we found that DC-SIGN selectively recognizes Mac-2BP derived from some colorectal carcinomas but not from the other ones. Furthermore, we found that the α1-3,4-fucose moieties of Le glycans expressed on DC-SIGN-binding Mac-2BP were important for recognition. DC-SIGN-dependent cellular interactions between immature MoDCs and colorectal carcinoma cells significantly inhibited MoDC functional maturation, suggesting that Mac-2BP may provide a tolerogenic microenvironment for colorectal carcinoma cells through DC-SIGN-dependent recognition. Importantly, Mac-2BP was detected as a predominant DC-SIGN ligand expressed on some primary colorectal cancer tissues from certain parts of patients in comparison with CEA from other parts, suggesting that DC-SIGN-binding Mac-2BP bearing tumor-associated Le glycans may become a novel potential colorectal cancer biomarker for some patients instead of CEA.