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1.
Indian J Gastroenterol ; 43(1): 215-225, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38244138

RESUMO

BACKGROUND: The transition from in-hospital intravenous administration to subcutaneous therapies to treat inflammatory bowel disease (IBD) can raise some concerns among patients due to the self-administration concerns, the management of potential side effects and the overall worries related to a change of treatment. This study aimed at evaluating patients' opinion about the switch from intravenous to subcutaneous formulations and their knowledge on new available therapeutic options. METHODS: We conducted a survey using a questionnaire prepared by a team of gastroenterologists and nurses working at the IBD unit. It consists of 31 items and has been divided into four sections: descriptive, commitment, knowledge and passage mode opinion. The questions were formulated in Italian and conceived according to daily consultations with patients in everyday practice, without any previous piloting or specific medical literature reference. The survey was administered to consecutive IBD patients in intravenous biological treatment; patients currently or previously treated with subcutaneous therapy were excluded. RESULTS: Four hundred questionnaires were distributed to participants. As many as 311 patients (77.7%) completed the survey, while the remaining were excluded from the analysis; 155 (49.8%) patients were favorable to switch from intravenous to subcutaneous therapy, while only 78 (25.1%) disagreed. In univariate and multi-variate analysis, the approval rate for home therapy was significantly associated with the distance from the IBD center and work/family/personal commitments. Surprisingly, only a quarter of the IBD patients knew that almost all available therapeutic agents have a subcutaneous administration route. Regarding patients' opinion on the efficacy of subcutaneous administration of biological agents compared to intravenous drugs, 194 (63%) had no definite idea, while 44 (14%) believed that the effectiveness could be reduced. CONCLUSION: The transition from in-hospital to subcutaneous therapeutic management of biological therapy at home was generally viewed favorably by patients, especially if they have commitments or were residents far from the IBD center.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Doença de Crohn/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Inquéritos e Questionários , Administração Intravenosa , Terapia Biológica , Colite Ulcerativa/tratamento farmacológico
2.
United European Gastroenterol J ; 11(7): 642-653, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37550901

RESUMO

BACKGROUND AND AIMS: The Diverticular Inflammation and Complication Assessment (DICA) classification and the Combined Overview on Diverticular Assessment (CODA) were found to be effective in predicting the outcomes of Diverticular Disease (DD). We ascertain whether fecal calprotectin (FC) can further aid in improving risk stratification. METHODS: A three-year international, multicentre, prospective cohort study was conducted involving 43 Gastroenterology and Endoscopy centres. Survival methods for censored observations were used to estimate the risk of acute diverticulitis (AD) in newly diagnosed DD patients according to basal FC, DICA, and CODA. The net benefit of management strategies based on DICA, CODA and FC in addition to CODA was assessed with decision curve analysis, which incorporates the harms and benefits of using a prognostic model for clinical decisions. RESULTS: At the first diagnosis of diverticulosis/DD, 871 participants underwent FC measurement. FC was associated with the risk of AD at 3 years (HR per each base 10 logarithm increase: 3.29; 95% confidence interval, 2.13-5.10) and showed moderate discrimination (c-statistic: 0.685; 0.614-0.756). DICA and CODA were more accurate predictors of AD than FC. However, FC showed high discrimination capacity to predict AD at 3 months, which was not maintained at longer follow-up times. The decision curve analysis comparing the combination of FC and CODA with CODA alone did not clearly indicate a larger net benefit of one strategy over the other. CONCLUSIONS: FC measurement could be used as a complementary tool to assess the immediate risk of AD. In all other cases, treatment strategies based on the CODA score alone should be recommended.


Assuntos
Doenças Diverticulares , Diverticulose Cólica , Divertículo , Humanos , Diverticulose Cólica/diagnóstico , Diverticulose Cólica/terapia , Diverticulose Cólica/complicações , Colonoscopia , Complexo Antígeno L1 Leucocitário , Estudos Prospectivos , Doenças Diverticulares/complicações , Doenças Diverticulares/diagnóstico , Doenças Diverticulares/terapia , Divertículo/complicações , Inflamação/diagnóstico , Inflamação/complicações
3.
Curr Drug Targets ; 19(7): 748-756, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-27231106

RESUMO

BACKGROUND: In the last decade, the introduction of the first anti-tumor necrosis factor (TNF)-α agent infliximab has revolutionized the treatment of ulcerative colitis (UC). However, this drug is not a magic bullet since up to 50% of UC patients do not respond (primary failure) or lose response to infliximab (secondary failure). Hence the demand for novel drugs to fill the unmet medical need. OBJECTIVE: The aim of this review is to discuss the data from randomized controlled trials (RCTs) of available biological agents for the treatment of moderate-to-severe UC in adults, in order to support clinical decision making. RESULTS AND CONCLUSION: New biological agents are now available for the treatment of moderate-tosevere UC. Adalimumab and golimumab are anti-TNF-α monoclonal antibodies, as is infliximab, whereas vedolizumab blocks the integrin α4ß7/mucosal addressin cell adhesion molucule-1 (MAd- CAM). Additions to the therapeutic arsenal boost the chances of successful treatment of UC, but lead to difficulty choosing the most appropriate biological drug: which biologic to use first and when and how to switch. In the absence of head-to-head trials to answer these questions, a network metaanalysis of the available RCTs can provide estimates of relative efficacy between interventions. Other factors, including convenience and satisfaction for the patient, route of administration, the cost of treatment, and the safety and efficacy profile, should all be considered.


Assuntos
Terapia Biológica/métodos , Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/administração & dosagem , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Colite Ulcerativa/fisiopatologia , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/farmacologia , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/farmacologia , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Infliximab/farmacologia , Satisfação do Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/antagonistas & inibidores
4.
World J Gastroenterol ; 22(24): 5505-11, 2016 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-27350728

RESUMO

Ulcerative colitis (UC) is a chronic inflammatory disease, whose etiology is still unclear. Its pathogenesis involves an interaction between genetic factors, immune response and the "forgotten organ", Gut Microbiota. Several studies have been conducted to assess the role of antibiotics and probiotics as additional or alternative therapies for Ulcerative Colitis. Escherichia coli Nissle (EcN) is a nonpathogenic Gram-negative strain isolated in 1917 by Alfred Nissle and it is the active component of microbial drug Mutaflor(®) (Ardeypharm GmbH, Herdecke, Germany and EcN, Cadigroup, In Italy) used in many gastrointestinal disorder including diarrhea, uncomplicated diverticular disease and UC. It is the only probiotic recommended in ECCO guidelines as effective alternative to mesalazine in maintenance of remission in UC patients. In this review we propose an update on the role of EcN 1917 in maintenance of remission in UC patients, including data about efficacy and safety. Further studies may be helpful for this subject to further the full use of potential of EcN.


Assuntos
Colite Ulcerativa/terapia , Escherichia coli , Probióticos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Colite Ulcerativa/microbiologia , Humanos , Quimioterapia de Manutenção , Mesalamina/uso terapêutico
5.
Dig Liver Dis ; 45(12): 1017-21, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23911613

RESUMO

BACKGROUND: Infliximab is effective in human and murine IBD, but its pharmacodynamic is still poorly known. The aim of this study was to assess the affinity of infliximab to murine TNF-α, its role in murine colitis when administered intra-rectally and its levels in the blood, gut mucosa and stool of healthy and sick mice. METHODS: An ELISA kit was built in order to assess the affinity of infliximab to human or murine-TNF-α. Human IgG were used as controls. DSS model of colitis on C57BL/6 mice was used to assess clinical efficacy of infliximab administered intravenously or by enema. Stool, serum and colon samples were collected to assess infliximab levels and histology for Rachmilewitz score. RESULTS: Infliximab showed a good affinity both for human-TNF-α and murine-TNF-α. In DSS colitic mice infliximab ameliorated the severity of colitis, regardless of the administration route. In comparison with colitic mice, healthy mice displayed higher serum and mucosal infliximab levels, while detectable levels of infliximab were found in faeces, particularly in colitic mice. CONCLUSION: Our data support murine models to study infliximab pharmacokinetics and dynamics. Measurable levels of infliximab can be found at different concentrations in blood, intestinal mucosa and stool from healthy and sick mice, thus infliximab pharmacokinetics could have a major impact in human IBD.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Colite/tratamento farmacológico , Fezes/química , Mucosa Intestinal/metabolismo , Administração Intravenosa , Administração Retal , Animais , Anti-Inflamatórios não Esteroides/análise , Anti-Inflamatórios não Esteroides/metabolismo , Anticorpos Monoclonais/análise , Anticorpos Monoclonais/metabolismo , Colite/induzido quimicamente , Colite/patologia , Sulfato de Dextrana , Enema , Infliximab , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/metabolismo
6.
Eur J Gastroenterol Hepatol ; 20(9): 826-8, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18794594

RESUMO

In both Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease (IBD), an increased risk of thrombotic events has been demonstrated. Pathogenesis of thrombosis is multifactorial as various primary coagulation system abnormalities other than acquired factors have been reported. The fibrinolytic system has been widely investigated in IBD. Most of the available data report an imbalance in fibrinolytic capacity with a tendency toward a hypofibrinolytic state. Plasma thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 are fundamental inhibitors of the fibrinolytic process and are also considered to be acute-phase reactants. Recent studies have shown an imbalance of plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor, suggesting that these molecules might contribute to thromboembolic events in both forms of IBD.


Assuntos
Carboxipeptidase B2/sangue , Doenças Inflamatórias Intestinais/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Fibrinólise , Hemostasia , Humanos
7.
Am J Gastroenterol ; 100(4): 886-95, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15784037

RESUMO

OBJECTIVES: Increased homocysteine contributes to the pathophysiology of several chronic inflammatory diseases. Whether homocysteine could participate in mucosal inflammation in inflammatory bowel disease (IBD) has not been explored yet. Our aims were to study the levels of plasma and mucosal homocysteine in IBD patients and to assess whether homocysteine can trigger an inflammatory reaction on human intestinal microvascular endothelial cells (HIMECs). METHODS: Homocysteine was measured in the plasma, mucosal biopsy, and lamina propria mononuclear cell (LPMC) supernatants from normal and IBD subjects. HIMEC were cultured in presence of homocysteine, TNF-alpha, or folic acid, alone or in combination. Expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular cell adhesion molecule 1 was measured by flow cytometry and monocyte chemoattractant protein-1 (MCP-1) production by ELISA. Phosphorylation of p38 and p42/44 was assessed by immunoblot in HIMEC extracts. T-cell- and monocyte-HIMEC adhesion assays were used to evaluate the impact of homocysteine on leukocyte adhesion to intestinal endothelial cells. RESULTS: Patients with IBD displayed significantly higher homocysteine plasma and mucosal levels than control subjects. IBD-derived LPMC released higher homocysteine than control-derived LPMC. Treatment of HIMEC with homocysteine, and synergistically with the combination of TNF-alpha and homocysteine, triggered HIMEC inflammation, resulting in VCAM-1 up-regulation, MCP-1 production, and p38 phosphorylation. These events lead to an increased capacity of HIMEC to adhere T- and monocyte cells and were blocked by folic acid treatment. CONCLUSIONS: Homocysteine is increased in both the mucosa and plasma of patients with Crohn's disease and ulcerative colitis and contributes to the inflammatory state of the mucosal IBD endothelium. Therefore, homocysteine could play a proinflammatory role in IBD, which can be efficiently targeted by folic acid supplementation.


Assuntos
Colite Ulcerativa/fisiopatologia , Doença de Crohn/fisiopatologia , Homocisteína/fisiologia , Mucosa Intestinal/irrigação sanguínea , Adolescente , Adulto , Idoso , Quimiocina CCL2/sangue , Endotélio Vascular/fisiopatologia , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Ácido Fólico/sangue , Humanos , Molécula 1 de Adesão Intercelular/sangue , Teste de Inibição de Aderência Leucocítica , Masculino , Microcirculação/fisiopatologia , Pessoa de Meia-Idade , Valores de Referência , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular/sangue
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