Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 45.317
Filtrar
Mais filtros











Intervalo de ano de publicação
1.
Rev Gastroenterol Peru ; 44(1): 26-34, 2024.
Artigo em Espanhol | MEDLINE | ID: mdl-38734909

RESUMO

INTRODUCTION: Attempts have been made to identify the genetic factors related to susceptibility to inflammatory bowel disease (IBD), and the current conclusions are in favor of a complex pathology model, without a clear hereditary pattern. OBJECTIVE: To perform phenotypic and genotypic characterization of patients with IBD in Colombian population and to describe its possible association with predisposition. MATERIALS AND METHODS: case series, 16 patients with IBD according to clinical and pathological criteria, onset of gastrointestinal symptoms after 18 years of age. All had pre-test genetic counseling and family trees of at least three generations were made. Also, genotyping, using a multi-gene panel that included genes related to IBD and some autoimmune disorders. Finally, a genomic analysis of variants was performed. RESULTS: 9 women and 7 men, with mean age of diagnosis of IBD of 35 years, and gastrointestinal symptoms appearance of 32 years. 11/16 (68.75%) required biological therapy. 10/16 (62.5%) were refractory to standard therapy. 3/16 (18.75%) had positive family history of IBD. 100% cases presented at least one single nucleotide polymorphism related to IBD risk in more than one gene. The genes most related to ulcerative colitis (UC) were CD48, CD6, and TYK2 for UC, and CD6 and ITGAM for Crohn's disease. The most frequent gene was CD6. It was found presence of up to 5 genes in 3/16 (18.75%), 4 in 3/16 (18.75%), and three in 5/16 (31.25%). CONCLUSION: In IBD there is the presence of genetic variants with associated predisposition, but without confirmed pathogenicity, and whose sum seems to contribute to its pathophysiology.


Assuntos
Predisposição Genética para Doença , Genótipo , Fenótipo , Humanos , Colômbia/epidemiologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Doenças Inflamatórias Intestinais/genética , Adolescente , Doença de Crohn/genética , Doença de Crohn/epidemiologia , Colite Ulcerativa/genética
3.
Tunis Med ; 102(4): 181-188, 2024 Apr 05.
Artigo em Francês | MEDLINE | ID: mdl-38746955

RESUMO

INTRODUCTION: Treatment of complex perianal fistulas in Crohn's disease remains a challenge especially after the failure of Infliximab. AIM: Update on the different therapeutic alternatives for anal fistula in Crohn's disease after failure of Infliximab. METHODS: A research in the medical literature on PubMed and Google Scholar was carried out. We included cohort studies, reviews and randomized double-blinded therapeutic trials. Case reports and fundamental research studies have been excluded. RESULTS: Anti-TNF therapy, notably Infliximab remain the therapeutic option of choice. Since Infliximab efficacy has been estimated at 60%, with a significant loss-of response rate, new therapeutic strategies have been evaluated and may offer new opportunities for the management of anal fistulas: for example, Ustekinumab could be effective after failure of anti-TNF therapy, although further studies are required. Recent guidelines suggest that injection of mesenchymal stem cells is an effective and safe treatment for complex fistulas. Other surgical options have been proposed, such as endorectal advancement flap, fibrin glue injection, anal fistula plug and ligation of the intersphincteric fistula tract, but all with limited and debatable efficacy. Given the failure rate of all these options, new strategies are currently being evaluated. CONCLUSION: Anal fistulas in Crohn's disease are a real therapeutic challenge. New medical and surgical therapies are currently being evaluated, with promising results.


Assuntos
Doença de Crohn , Fármacos Gastrointestinais , Infliximab , Fístula Retal , Falha de Tratamento , Humanos , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Fístula Retal/etiologia , Fístula Retal/tratamento farmacológico , Fístula Retal/terapia , Infliximab/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Fármacos Gastrointestinais/administração & dosagem
4.
Ned Tijdschr Geneeskd ; 1682024 May 06.
Artigo em Holandês | MEDLINE | ID: mdl-38747608

RESUMO

Multiple sclerosis is a chronic inflammatory disease of the central nervous system, caused by an autoimmune reaction. Treatment options have largely increased over the years. In this article, we present two clinical cases. Patient A has a classic relapsing remitting course of multiple sclerosis with satisfactory effect on second line therapy. Patient B had a stable disease course until a new relapse occurred after the initiation of TNF-alpha blocking therapy because of Crohn's disease. The co-occurrence of multiple auto-immune diseases creates challenges, but also opportunities in choosing the right treatment strategy.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Humanos , Adulto , Feminino , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Resultado do Tratamento , Esclerose Múltipla/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Doença de Crohn/tratamento farmacológico , Masculino , Imunossupressores/uso terapêutico
5.
Clin Neuropharmacol ; 47(3): 104-107, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38743605

RESUMO

OBJECTIVES: Metronidazole central nervous system toxicity is a rare finding in patients receiving the medication. We report a peculiar case of metronidazole central nervous system toxicity in which both the underlying condition (Crohn disease) and the drugs used to treat it are potential causes of encephalopathy. METHODS: A 26-year-old female with 6-year history of Crohn's disease for 6 years presented acute-onset encephalopathy. We provide bibliographic evidence to support metronidazole toxicity and potential Crohn disease-associated neurologic involvement. RESULTS: The patient presented dystonia, cerebellar ataxia, and altered mental status. Magnetic resonance imaging of the brain revealed typical findings of metronidazole toxicity and white matter involvement of the centrum semiovale. Immunoelectrophoresis and immunofixation of serum and cerebrospinal fluid proteins were consistent with a systemic inflammatory process. We concluded on an association between drug toxicity and probable Crohn-associated neurologic involvement. Metronidazole was stopped and the patient was placed on vitamin therapy and diazepam to control dystonia. She deteriorated and was transferred to the intensive care unit where she expired. CONCLUSIONS: Acute behavioral changes in a young patient constitute an emergency and differential diagnoses should include infective, inflammatory, metabolic, and toxic causes. Metronidazole is a potential toxic etiology.


Assuntos
Doença de Crohn , Encefalite , Metronidazol , Humanos , Metronidazol/efeitos adversos , Feminino , Doença de Crohn/tratamento farmacológico , Doença de Crohn/complicações , Adulto , Encefalite/induzido quimicamente , Encefalopatias/induzido quimicamente , Imageamento por Ressonância Magnética , Evolução Fatal
6.
Stem Cell Res Ther ; 15(1): 140, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745184

RESUMO

BACKGROUND: Perianal fistulas (PF) affect one-third patients with Crohn's disease (CD) with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) in this population. METHODS: An open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn's disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically until week 104 , and MRI at week 24 and 104. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with < 2 cm perianal collection on MRI, and fistula response was decrease in drainage by ≥ 50%. Change in perianal disease activity index, quality-of-life and Van Assche index on MRI over time was assessed using mixed-effect linear regression model. RESULTS: Ten patients (male:8, mean age:27.4 ± 12.0years) were recruited. Self-resolving procedure-related adverse events occurred in three patients, with no follow-up adverse events. In intention to treat analysis at week 24, two patients (20%) achieved fistula remission and seven (70%) had fistula response. At week 52, two (20%) patients were in remission and seven (70%) maintained response. At 104 weeks, two (20%) patients maintained response and one (10%) was in remission. Statistically significant decrease in perianal disease activity index (P = 0.008), Van Assche Index (P = 0.008) and improvement in quality-of-life (P = 0.001) were observed over time. CONCLUSIONS: Allogeneic BMSCs are safe and effective for the treatment of perianal fistulizing CD with significant improvement in clinical severity and radiological healing. TRIAL REGISTRATION: The study was prospectively registered on Clinical trials registry - India (CTRI), CTRI/2020/01/022743 on 14 January 2020, http://ctri.nic.in .


Assuntos
Doença de Crohn , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Fístula Retal , Humanos , Doença de Crohn/complicações , Doença de Crohn/terapia , Masculino , Adulto , Feminino , Transplante de Células-Tronco Mesenquimais/métodos , Fístula Retal/terapia , Fístula Retal/etiologia , Células-Tronco Mesenquimais/citologia , Adulto Jovem , Transplante Homólogo/métodos , Adolescente , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética , Resultado do Tratamento , Qualidade de Vida
7.
J Med Case Rep ; 18(1): 246, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38741148

RESUMO

INTRODUCTION: Thrombotic events are more than twice as common in inflammatory bowel disease patients as in the general population. We report an interesting and rare case of portal vein thrombosis as a venous thromboembolic event in the context of extraintestinal manifestations of Crohn's disease. We also conducted a literature review on portal vein thrombosis associated with inflammatory bowel disease, with the following concepts: inflammatory bowel diseases, ulcerative colitis, Crohn's disease, portal vein, and thrombosis. CASE PRESENTATION: A 24-year-old Syrian female with active chronic Crohn's disease was diagnosed 11 years ago and classified as A1L3B1P according to the Montreal classification. She had no prior surgical history. Her previous medications included azathioprine and prednisolone. Her Crohn's disease activity index was 390 points. Gastroduodenoscopy revealed grade I esophageal varices, a complication of portal hypertension. Meanwhile, a colonoscopy revealed several deep ulcers in the sigmoid, rectum, and descending colon. An investigation of portal vein hypertension revealed portal vein thrombosis. We used corticosteroids to induce remission, followed by tapering; additionally she received ustekinumab to induce and maintain remission. She began on low-molecular-weight heparin for 1 week, warfarin for 3 months, and then apixaban, a novel oral anticoagulant, after excluding antiphospholipid syndrome. Primary prophylaxis for esophageal varices was not required. After 1 year, she achieved clinical, biochemical, and endoscopic remission. Despite 1 year of treatment, a computed tomography scan revealed no improvement in portal vein recanalization. CONCLUSION: Portal vein thrombosis is a rare and poorly defined complication of inflammatory bowel disease. It is usually exacerbated by inflammatory bowel disease. The symptoms are nonspecific and may mimic a flare-up of inflammatory bowel disease, making the diagnosis difficult. Portal vein Doppler ultrasound for hospital-admitted inflammatory bowel disease patients may contribute to the diagnosis and management of this complication.


Assuntos
Anticoagulantes , Doença de Crohn , Veia Porta , Trombose Venosa , Humanos , Doença de Crohn/complicações , Feminino , Veia Porta/diagnóstico por imagem , Trombose Venosa/etiologia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/tratamento farmacológico , Adulto Jovem , Anticoagulantes/uso terapêutico , Varfarina/uso terapêutico
8.
BMC Med Educ ; 24(1): 529, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741179

RESUMO

BACKGROUND AND AIMS: Management of inflammatory bowel disease is constantly evolving, increasing the importance for gastroenterologists to keep up to date with guidelines. Traditional implementation strategies have had only small positive impacts on clinical practice. eHealth strategies such as the European Crohn's and Colitis Organisation e-guide may be beneficial for clinician decision making in keeping with guidelines. The aim of this study was to evaluate the feasibility and acceptability of the e-guide. METHODS: A mixed methods approach was used to evaluate feasibility and acceptability. Cognitive (think-aloud) interviews were conducted with Australian gastroenterologists while using the e-guide. Two clinical scenarios were developed to allow evaluation of various aspects of the e-guide. Content analysis was applied to the qualitative interview data and descriptive analysis to the quantitative and observational data. RESULTS: Seventeen participants completed the study. Data saturation were reached. The ECCO e-guide was largely feasible and acceptable, as demonstrated by most clinical questions answered correctly, 87% reaching the answer within 3 min, and most feeling it was useful, would be beneficial to their practice and would use it again. Issues raised included difficulties with website navigation, layout of the e-guide and difficulties with access (network firewalls, paid subscription required). CONCLUSIONS: The ECCO e-guide is largely acceptable and feasible for gastroenterologists to use. Aspects of the e-guide could be modified to improve user experience. This study highlights the importance of engaging end-users in the development and evaluation of clinician educational tools.


Assuntos
Doença de Crohn , Estudos de Viabilidade , Gastroenterologistas , Fidelidade a Diretrizes , Humanos , Austrália , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Europa (Continente) , Atitude do Pessoal de Saúde , Gastroenterologia
9.
Front Immunol ; 15: 1352712, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707907

RESUMO

Background: Inflammatory bowel disease is an incurable group of recurrent inflammatory diseases of the intestine. Mendelian randomization has been utilized in the development of drugs for disease treatment, including the therapeutic targets for IBD that are identified through drug-targeted MR. Methods: Two-sample MR was employed to explore the cause-and-effect relationship between multiple genes and IBD and its subtypes ulcerative colitis and Crohn's disease, and replication MR was utilized to validate this causality. Summary data-based Mendelian randomization analysis was performed to enhance the robustness of the outcomes, while Bayesian co-localization provided strong evidential support. Finally, the value of potential therapeutic target applications was determined by using the estimation of druggability. Result: With our investigation, we identified target genes associated with the risk of IBD and its subtypes UC and CD. These include the genes GPBAR1, IL1RL1, PRKCB, and PNMT, which are associated with IBD risk, IL1RL1, with a protective effect against CD risk, and GPX1, GPBAR1, and PNMT, which are involved in UC risk. Conclusion: In a word, this study identified several potential therapeutic targets associated with the risk of IBD and its subtypes, offering new insights into the development of therapeutic agents for IBD.


Assuntos
Predisposição Genética para Doença , Doenças Inflamatórias Intestinais , Análise da Randomização Mendeliana , Humanos , Doenças Inflamatórias Intestinais/genética , Polimorfismo de Nucleotídeo Único , Doença de Crohn/genética , Doença de Crohn/tratamento farmacológico , Teorema de Bayes , Colite Ulcerativa/genética , Terapia de Alvo Molecular
10.
Front Immunol ; 15: 1374107, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38720886

RESUMO

Background: Eosinophilic esophagitis (EoE) and inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are immune-mediated gastrointestinal diseases with overlapped pathogenesis and are sometimes concurrently diagnosed, but their causal relationship remains unclear. We investigated the causal relationship between EoE and IBD and its subtypes via a two-sample bidirectional Mendelian randomization (MR) approach. Methods: MR analyses were performed using summary data of a genome-wide association study (GWAS) on individuals of European ancestry. Independent single-nucleotide polymorphisms correlated with EoE (from a GWAS meta-analysis containing 1,930 cases and 13,634 controls) and IBD (from FinnGen GWASs containing 9,083 IBD, 2,033 CD, and 5,931 UC cases, and GWASs of IBD genetic consortium containing 12,882 IBD, 6,968 UC, and 5,956 CD cases) were selected as instruments. We applied the inverse variance weighted (IVW) method as the primary analysis followed by several sensitivity analyses. For the forward MR study, estimates from IVW methods were subsequently meta-analyzed using a random-effect model. Results: Our results suggested a causal effect of EoE on IBD [pooled odds ratio (OR), 1.07; 95% confidence interval (CI), 1.02-1.13] and EoE on UC (pooled OR, 1.09, 95% CI, 1.04-1.14). No causal link between EoE and CD was observed (pooled OR, 1.05; 95% CI, 0.96-1.16). The reverse MR analyses revealed no causal effect of IBD (and its subtypes) on EoE. Sensitivity analyses confirmed the robustness of primary results. Conclusions: Our findings provided evidence of a suggestive causal effect of EoE on IBD (specifically on UC) in the European population. Increased awareness of concurrent or subsequent IBD in patients with EoE is called for. Still, the present evidence is not adequate enough and ought to be validated by further investigations.


Assuntos
Esofagite Eosinofílica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Doenças Inflamatórias Intestinais , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Humanos , Esofagite Eosinofílica/genética , Esofagite Eosinofílica/epidemiologia , Esofagite Eosinofílica/etiologia , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/etiologia , Doença de Crohn/genética , Doença de Crohn/epidemiologia
11.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(4): 765-772, 2024 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-38708511

RESUMO

OBJECTIVE: To investigate the expression level of Kruppel-like transcription factor family member KLF11 in intestinal mucosal tissues of Crohn's disease (CD) and its regulatory effect on intestinal inflammation in CD-like colitis. METHODS: We examined KLF11 expression levels in diseased and normal colon mucosal tissues from 12 CD patients and 12 patients with colorectal cancer using immunofluorescence staining. KLF11 expression was also detected in the colon mucosal tissues of a mouse model of 2, 4, 6-trinitrobenesulfonic acid (TNBS)-induced colitis. A recombinant adenoviral vector was used to upregulate KLF11 expression in the mouse models and the changes in intestinal inflammation was observed. A Caco-2 cell model with stable KLF11 overexpression was constructed by lentiviral infection. The effect of KLF11 overexpression on expressions of JAK2/STAT3 signaling pathway proteins was investigated using immunoblotting in both the mouse and cell models. The mouse models were treated with coumermycin A1, a JAK2/STAT3 signaling pathway agonist, and the changes in intestinal inflammatory responses were observed. RESULTS: The expression level of KLF11 was significantly lowered in both the clinical specimens of diseased colon mucosal tissues and the colon tissues of mice with TNBS-induced colitis (P < 0.05). Adenovirus-mediated upregulation of KLF11 significantly improved intestinal inflammation and reduced the expression levels of inflammatory factors in the intestinal mucosa of the colitis mouse models (P < 0.05). Overexpression of KLF11 significantly inhibited the expression levels of p-JAK2 and p-STAT3 in intestinal mucosal tissues of the mouse models and in Caco-2 cells (P < 0.05). Treatment with coumermycin A1 obviously inhibited the effect of KLF11 upregulation for improving colitis and significantly increased the expression levels of inflammatory factors in the intestinal mucosa of the mouse models (P < 0.05). CONCLUSION: KLF11 is downregulated in the intestinal mucosa in CD, and upregulation of KLF11 can improve intestinal inflammation and reduce the production of inflammatory factors probably by inhibiting the JAK2/STAT3 signaling pathway.


Assuntos
Proteínas Reguladoras de Apoptose , Colite , Mucosa Intestinal , Janus Quinase 2 , Proteínas Repressoras , Fator de Transcrição STAT3 , Transdução de Sinais , Ácido Trinitrobenzenossulfônico , Animais , Camundongos , Colite/induzido quimicamente , Colite/metabolismo , Humanos , Fator de Transcrição STAT3/metabolismo , Janus Quinase 2/metabolismo , Células CACO-2 , Mucosa Intestinal/metabolismo , Modelos Animais de Doenças , Doença de Crohn/metabolismo , Inflamação/metabolismo , Regulação para Cima , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética
12.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(5): 455-459, 2024 May 12.
Artigo em Chinês | MEDLINE | ID: mdl-38706068

RESUMO

Here we reported a case of a 52-year-old male with a 13-year history of Crohn's disease who developed disseminated tuberculosis after 2 injections of infliximab. The patient was admitted with a chief complaint of fever with headache of 1 month's duration. Mycobacterium tuberculosis DNA was found positive in cerebrospinal fluid and lavage fluid by lumbar puncture and bronchoscopy. He was diagnosed with tuberculous meningitis, pulmonary tuberculosis, tracheobronchial tuberculosis and lymph node tuberculosis. After treatment with anti-tuberculosis and glucocorticoids, the symptoms did not improve, the lesions progressed, and granulomas were formed in the tracheobronchial lumen. These were considered to be contradictory reactions and thalidomide was given together with glucocorticoids. The patient's clinical condition has improved significantly. Treatment was successfully completed after 18 months with 1 HREZLfxLzd/8 HEZCsLzd/1 HEZCs/8 HZCs.


Assuntos
Talidomida , Humanos , Masculino , Pessoa de Meia-Idade , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Doença de Crohn/tratamento farmacológico , Tuberculose/tratamento farmacológico
13.
J Manag Care Spec Pharm ; 30(5): 420-429, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38701028

RESUMO

BACKGROUND: Population-based studies for patients with fistulizing Crohn disease (CD), a severe complication of CD, are limited. OBJECTIVE: To report estimates of the prevalence and incidence rates of fistulizing CD in the United States and examine associated treatment patterns among incident cases. METHODS: This retrospective, observational cohort study used a US administrative claims database from January 1, 2016, to December 31, 2019, with at least 365 days' continuous insurance enrollment. The prevalent patient population comprised patients with incident or existing cases of fistulizing CD. Crude, age, and sex-adjusted prevalence and incidence rates of fistulizing CD were estimated. Baseline characteristics, comorbidities, and CD-related medications and medical procedures were examined for patients with fistulizing CD. RESULTS: The overall crude prevalence (prevalent cases: n = 5,082) and incidence rates (incident cases: n = 2,399) between 2017 and 2019 were 25.2 (95% CI = 24.5-25.9) per 100,000 persons and 6.9 (95% CI = 6.6-7.1) per 100,000 person-years, respectively. Age- and sex-adjusted prevalence and incidence rates were 24.9 (95% CI = 24.2-25.6) per 100,000 persons and 7.0 (95% CI = 6.7-7.3) per 100,000 person-years, respectively. Approximately half of all patients with incident fistulizing CD were prescribed biologic therapies within 1 year of an incident fistula diagnosis, with anti-tumor necrosis factor therapies the most widely prescribed biologic class; antibiotic and corticosteroid use was also common. Among the incident cases, approximately one-third of patients required surgery during the follow-up period, most of which occurred within 3 months of the index date. CONCLUSIONS: This study reports age- and sex-adjusted prevalence and incidence rates for fistulizing CD of 24.9 per 100,000 persons and 7.0 per 100,000 person-years, respectively. As a concerning complication of CD, first-year treatment of fistulas in the United States commonly includes anti-tumor necrosis factor therapy, and there is a considerable surgical burden.


Assuntos
Doença de Crohn , Humanos , Doença de Crohn/epidemiologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/terapia , Masculino , Feminino , Incidência , Adulto , Estudos Retrospectivos , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Prevalência , Adulto Jovem , Adolescente , Estudos de Coortes , Fístula Intestinal/epidemiologia , Idoso
14.
Nat Commun ; 15(1): 3764, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704361

RESUMO

Crohn disease (CD) burden has increased with globalization/urbanization, and the rapid rise is attributed to environmental changes rather than genetic drift. The Study Of Urban and Rural CD Evolution (SOURCE, n = 380) has considered diet-omics domains simultaneously to detect complex interactions and identify potential beneficial and pathogenic factors linked with rural-urban transition and CD. We characterize exposures, diet, ileal transcriptomics, metabolomics, and microbiome in newly diagnosed CD patients and controls in rural and urban China and Israel. We show that time spent by rural residents in urban environments is linked with changes in gut microbial composition and metabolomics, which mirror those seen in CD. Ileal transcriptomics highlights personal metabolic and immune gene expression modules, that are directly linked to potential protective dietary exposures (coffee, manganese, vitamin D), fecal metabolites, and the microbiome. Bacteria-associated metabolites are primarily linked with host immune modules, whereas diet-linked metabolites are associated with host epithelial metabolic functions.


Assuntos
Doença de Crohn , Dieta , Microbioma Gastrointestinal , População Rural , População Urbana , Doença de Crohn/microbiologia , Doença de Crohn/genética , Humanos , Masculino , Feminino , China/epidemiologia , Adulto , Israel/epidemiologia , Metabolômica , Estudos de Coortes , Pessoa de Meia-Idade , Fezes/microbiologia , Íleo/microbiologia , Íleo/metabolismo , Transcriptoma , Adulto Jovem
15.
Ugeskr Laeger ; 186(18)2024 Apr 29.
Artigo em Dinamarquês | MEDLINE | ID: mdl-38704716

RESUMO

Ulcerative colitis and Crohn's disease are chronic inflammatory bowel diseases. Recent pivotal phase 3 trials involving treatments like interleukin-23-, sphingosin-1-phosphate- and Janus kinase inhibitors have demonstrated notable effectiveness. However, they have also unveiled significant side effects such as herpes zoster, lymphopenia and bradycardia. The introduction of novel treatments raises valid concerns necessitating increased collaboration with diverse medical specialities to address potentially severe side effects, and this is vital for enhancing the future care of individuals with inflammatory bowel diseases, as argued in this review.


Assuntos
Produtos Biológicos , Colite Ulcerativa , Doença de Crohn , Humanos , Doença de Crohn/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Inibidores de Janus Quinases/uso terapêutico , Moduladores do Receptor de Esfingosina 1 Fosfato/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos
16.
BMC Surg ; 24(1): 130, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38698365

RESUMO

BACKGROUND: Anastomosis configuration is an essential step in treatment to restore continuity of the gastrointestinal tract following bowel resection in patients with Crohn's disease (CD). However, the association between anastomotic type and surgical outcome remains controversial. This retrospective study aimed to compare early postoperative complications and surgical outcome between stapler and handsewn anastomosis after bowel resection in Crohn's disease. METHODS: Between 2001 and 2018, a total of 339 CD patients underwent bowel resection with anastomosis. Patient characteristics, intraoperative data, early postoperative complications, and outcomes were analyzed and compared between two groups of patients. Group 1 consisted of patients with stapler anastomosis and group 2 with handsewn anastomosis. RESULTS: No significant difference was found in the incidence of postoperative surgical complications between the stapler and handsewn anastomosis groups (25% versus 24.4%, p = 1.000). Reoperation for complications and postoperative hospital stay were similar between the two groups. CONCLUSION: Our analysis showed that there were no differences in anastomotic leak, nor postoperative complications, mortality, reoperation for operative complications, or postoperative hospital stay between the stapler anastomosis and handsewn anastomosis groups.


Assuntos
Anastomose Cirúrgica , Doença de Crohn , Complicações Pós-Operatórias , Grampeamento Cirúrgico , Humanos , Doença de Crohn/cirurgia , Feminino , Masculino , Anastomose Cirúrgica/métodos , Estudos Retrospectivos , Adulto , Grampeamento Cirúrgico/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pessoa de Meia-Idade , Técnicas de Sutura , Reoperação/estatística & dados numéricos , Resultado do Tratamento , Tempo de Internação/estatística & dados numéricos , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Adulto Jovem
18.
Nihon Yakurigaku Zasshi ; 159(3): 150-155, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38692877

RESUMO

Crohn's disease (CD) is a chronic and relapsing inflammatory bowel disease affecting the entire gastrointestinal tract. The prevalence of CD among Japanese people is increasing. One of the most frequent complications of CD is perianal fistulas. People living with CD may experience complex perianal fistulas, which can cause intense pain, bleeding, swelling, infection, and anal discharge. Despite medical and surgical advancements, complex perianal fistulas in CD remain challenging for clinicians to treat. CD patients living with perianal fistulas reported a negative impact on many aspects of their quality of life. Darvadstrocel is a cell therapy product containing a suspension of allogeneic expanded adipose-derived mesenchymal stem cells. It has been approved in Europe and Japan for the treatment of complex perianal fistulas that have shown an inadequate response to at least one conventional or biologic therapy in adult patients with non-active/mildly active luminal CD. By exhibiting immunomodulatory and local anti-inflammatory effects at the site of inflammation, it offers a new treatment option for complex perianal fistulas in CD patients. In this manuscript, the characteristic of darvadstrocel, the summary of results from the pivotal phase 3 studies in Europe and Japan, and the development strategy in Japan were introduced.


Assuntos
Doença de Crohn , Transplante de Células-Tronco Mesenquimais , Fístula Retal , Doença de Crohn/terapia , Doença de Crohn/complicações , Humanos , Fístula Retal/terapia , Fístula Retal/etiologia , Japão , Células-Tronco Mesenquimais , Tecido Adiposo
19.
FASEB J ; 38(9): e23627, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38690708

RESUMO

Colonoscopy is the gold standard for diagnosing inflammatory bowel disease (IBD). However, this invasive procedure has a high burden for pediatric patients. Previous research has shown elevated fecal amino acid concentrations in children with IBD versus controls. We hypothesized that this finding could result from increased proteolytic activity. Therefore, the aim of this study was to investigate whether fecal protease-based profiling was able to discriminate between IBD and controls. Protease activity was measured in fecal samples from patients with IBD (Crohn's disease (CD) n = 19; ulcerative colitis (UC) n = 19) and non-IBD controls (n = 19) using a fluorescence resonance energy transfer (FRET)-peptide library. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of each FRET-peptide substrate. Screening the FRET-peptide library revealed an increased total proteolytic activity (TPA), as well as degradation of specific FRET-peptides specifically in fecal samples from IBD patients. Based on level of significance (p < .001) and ROC curve analysis (AUC > 0.85), the fluorogenic substrates W-W, A-A, a-a, F-h, and H-y showed diagnostic potential for CD. The substrates W-W, a-a, T-t, G-v, and H-y showed diagnostic potential for UC based on significance (p < .001) and ROC analysis (AUC > 0.90). None of the FRET-peptide substrates used was able to differentiate between protease activity in fecal samples from CD versus UC. This study showed an increased fecal proteolytic activity in children with newly diagnosed, treatment-naïve, IBD. This could lead to the development of novel, noninvasive biomarkers for screening and diagnostic purposes.


Assuntos
Fezes , Doenças Inflamatórias Intestinais , Proteólise , Humanos , Fezes/química , Fezes/enzimologia , Criança , Feminino , Masculino , Projetos Piloto , Adolescente , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/diagnóstico , Colite Ulcerativa/metabolismo , Colite Ulcerativa/diagnóstico , Transferência Ressonante de Energia de Fluorescência/métodos , Peptídeo Hidrolases/metabolismo , Doença de Crohn/diagnóstico , Doença de Crohn/metabolismo , Curva ROC , Estudos de Casos e Controles , Pré-Escolar
20.
World J Gastroenterol ; 30(16): 2184-2190, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38690020

RESUMO

MicroRNAs (miRNAs), small non-coding RNAs composed of 18-24 nucleotides, are potent regulators of gene expression, contributing to the regulation of more than 30% of protein-coding genes. Considering that miRNAs are regulators of inflammatory pathways and the differentiation of intestinal epithelial cells, there is an interest in exploring their importance in inflammatory bowel disease (IBD). IBD is a chronic and multifactorial disease of the gastrointestinal tract; the main forms are Crohn's disease and ulcerative colitis. Several studies have investigated the dysregulated expression of miRNAs in IBD, demonstrating their important roles as regulators and potential biomarkers of this disease. This editorial presents what is known and what is expected regarding miRNAs in IBD. Although the important regulatory roles of miRNAs in IBD are clearly established, biomarkers for IBD that can be applied in clinical practice are lacking, emphasizing the importance of further studies. Discoveries regarding the influence of miRNAs on the inflammatory process and the exploration of their role in gene regulation are expected to provide a basis for the use of miRNAs not only as potent biomarkers in IBD but also as therapeutic targets for the control of inflammatory processes in personalized medicine.


Assuntos
Biomarcadores , Regulação da Expressão Gênica , MicroRNAs , Humanos , MicroRNAs/metabolismo , MicroRNAs/genética , Biomarcadores/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Doença de Crohn/genética , Doença de Crohn/imunologia , Doença de Crohn/metabolismo , Colite Ulcerativa/genética , Colite Ulcerativa/imunologia , Colite Ulcerativa/metabolismo , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/terapia , Doenças Inflamatórias Intestinais/imunologia , Medicina de Precisão/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA