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BACKGROUND: Ulcerative colitis (UC) is an idiopathic, chronic inflammatory bowel disease (IBD) most often located in the rectum, but may involve the entire colon. Extra intestinal manifestations (EIMs) occur with varying frequency depending on the affected organ. The most common ones are musculoskeletal EIMs, affecting up to 33%-40% of IBD patients. These include, among others, inflammatory back pain, tendinitis, plantar fasciitis and arthritis. Only a few case reports in literature discuss Achilles tendinitis. CASE SUMMARY: This report describes a patient with UC and Achilles tendinitis in whom after many unsuccessful attempts of treatment with sulfasalazine, mesalazine, glucocorticosteroids, infliximab and tofacitinib, a complete UC remission and resolution of Achilles tendinitis were achieved with the use of dual biologic therapy (DBT)-ustekinumab and adalimumab (ADA). CONCLUSION: This case mentions rare EIMs of UC and suggests that DBT may be an alternative for patient with ulcerative colitis and EIMs.
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BACKGROUND: Mast cell leukemia (MCL), a subtype of systemic mastocytosis (SM), is an extremely rare clinical entity characterized by a very poor prognosis. Chemotherapy, tyrosine kinase inhibitors, and allogeneic hematopoietic cell transplantation are the only treatment options, but they cannot provide the desired outcomes in most cases of MCL. However, other types of SM can be successfully treated. The disease has no specific manifestation, but gastroenterological symptoms are present in most cases. CASE SUMMARY: The authors, hereby, report a case of a 46-year-old female patient diagnosed with MCL-the rarest subtype of SM. The patient presented to the gastroenterology clinic with multiple, various, and unspecific gastroenterological symptoms. Concomitance of skin lesions significantly contributed to a relatively prompt diagnosis. The serum tryptase level was extremely high and bone the marrow aspirate showed an infiltration of atypical mast cells. The disease was rapidly progressive and primary refractory to chemotherapy and the patient succumbed to the illness about a month after the initiation of treatment. CONCLUSION: Despite its "hematological nature", MCL, in most cases presents dominantly with unspecific gastroenterological symptoms. Thus, a high disease awareness among physicians other than hematologists is necessary to improve treatment outcomes. Serum tryptase level, due to its non-invasive nature and easy access, may serve as an initial step to estimate the probability of mastocytosis.
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BACKGROUND & AIMS: CT-P13 subcutaneous (SC), an SC formulation of the intravenous (IV) infliximab biosimilar CT-P13 IV, creates a unique exposure profile. The LIBERTY studies aimed to demonstrate superiority of CT-P13 SC vs placebo as maintenance therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Two randomized, placebo-controlled, double-blind studies were conducted in patients with moderately to severely active CD or UC and inadequate response or intolerance to corticosteroids and immunomodulators. All patients received open-label CT-P13 IV 5 mg/kg at weeks 0, 2, and 6. At week 10, clinical responders were randomized (2:1) to CT-P13 SC 120 mg or placebo every 2 weeks until week 54 (maintenance phase) using prefilled syringes. (Co-) primary end points were clinical remission and endoscopic response (CD) and clinical remission (UC) at week 54 (all-randomized population). RESULTS: Overall, 396 patients with CD and 548 patients with UC received induction treatment. At week 54 in the CD study, statistically significant higher proportions of CT-P13 SC-treated patients vs placebo-treated patients achieved clinical remission (62.3% vs 32.1%; P < .0001) and endoscopic response (51.1% vs 17.9%; P < .0001). In the UC study, clinical remission rates at week 54 were statistically significantly higher with CT-P13 SC vs placebo (43.2% vs 20.8%; P < .0001). Achievement of key secondary end points was significantly higher with CT-P13 SC vs placebo across both studies. CT-P13 SC was well tolerated, with no new safety signals identified. CONCLUSIONS: CT-P13 SC was more effective than placebo as maintenance therapy and was well tolerated in patients with moderately to severely active CD or UC who responded to CT-P13 IV induction. CLINICALTRIALS: gov, Numbers: NCT03945019 (CD) and NCT04205643 (UC).
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This paper is an update of the diagnostic and therapeutic recommendations of the National Consultant for Gastroenterology and the Polish Society of Gastroenterology from 2013. It contains 49 recommendations for the diagnosis and treatment, both pharmacological and surgical, of ulcerative colitis in adults. The guidelines were developed by a group of experts appointed by the Polish Society of Gastroenterology and the National Consultant in the field of Gastroenterology. The methodology related to the GRADE methodology was used to assess the quality of available evidence and the strength of therapeutic recommendations. The degree of expert support for the proposed statements was assessed on a 6-point Likert scale. Voting results, together with comments, are included with each statement.
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Background: Type 2 autoimmune polyendocrine syndrome (APS-2) is characterized by the presence of at least two of three endocrinopathies: Addison's disease, autoimmune thyroiditis, and diabetes type 1. The prevalence of APS-2 is estimated to be 1 : 1000 to 1 : 20.000 in the general population. Diagnosis of APS-2 often is delayed due to its rarity and wide spectrum of clinical symptoms. Case Presentation. A 27-year-old presented with a 6-month history of abdominal pain, vomiting, diarrhea, weakness, fatigue, and 15 kg of weight loss. The patient was diagnosed with Crohn's disease in a local hospital and referred to our institution because of treatment failure. Colonoscopy performed in this hospital identified irregular mucosal erosions in terminal ileum, and the microscopy of biopsy specimens demonstrated nonspecific inflammation. On physical examination, the patient appeared cachectic. Blood pressure was 90/60 mmHg. Laboratory results were significant for severe hyponatremia and mild hyperkalemia. Morning cortisol was low, and adrenocorticotropic hormone (ACTH) concentration was high. An ACTH stimulation test did not present any increase in serum cortisol, which confirmed primary adrenal insufficiency. Antithyroid peroxidase antibody (anti-TPO) as well as both anti-21-hydroxylase antibodies and antiglutamic acid decarboxylase antibodies (GAD65) were positive. So, the diagnosis of APS-2 was made, and the replacement doses of hydrocortisone and fludrocortisone has brought a rapid improvement in all clinical symptoms; colonoscopy showed normal. Conclusion: The case presented herein highlights rapidly progressive nature of untreated APS-2 and that the diagnosis of APS-2 may be challenging.
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BACKGROUND Pancreatic cancer is one of the most common cancers in the world and a major cause of cancer mortality. Therefore, it is extremely important to distinguish between malignant and benign changes quickly and accurately. This single-center study aimed to assess the discriminatory properties of the color Doppler vascularity index (CDVI) in the diagnosis of focal chronic pancreatitis and malignant pancreatic tumors. MATERIAL AND METHODS Seventy-nine patients (42 men, 37 women; age 62.0±13.5 years; 46 adenocarcinomas; 33 pancreatitis) qualified for this study. During endosonographic examination, pancreatic tumors were assessed in the color Doppler option. The dynamic tissue perfusion measurement was used to calculate tissue flow velocity (TFV), tissue perfusion intensity (TPI), and vascularization as the CDVI. RESULTS TFV, TPI, and CDVI were significantly lower in the group with malignant tumors than in the group with pancreatitis (P<0.001). In the receiver operating characteristic analysis, results of TFV=2.181 cm/s, TPI=0.009 cm/s, and CDVI=0.268 allowed for significant prediction of malignant tumors (P<0.001), with sensitivity of 75.8%, 69.7%, and 72.7% and specificity of 91.3%, 93.5%, and 80.4%, respectively, without significant differences between perfusion parameters and CDVI (P=0.07). CONCLUSIONS The findings from this study showed that color Doppler imaging and the use of the CDVI could provide an adjunctive diagnostic approach to distinguish between pancreatic adenocarcinoma and focal chronic pancreatitis. Owing to the possibility of calculating vascularization by non-Doppler methods, the method may be an easier and more accessible diagnostic option for malignant pancreatic tumors than perfusion assessed in external software.
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Adenocarcinoma/diagnóstico , Endossonografia/métodos , Neoplasias Pancreáticas/diagnóstico , Ultrassonografia Doppler em Cores/métodos , Adenocarcinoma/epidemiologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Neoplasias Pancreáticas/epidemiologia , Polônia/epidemiologia , Curva ROCRESUMO
Dynamic tissue perfusion measurement (DTPM) and single vessel flow measurement (SVFM) were assessed in differentiating inflammatory and malignant lesions of the pancreas. Sixty-nine patients (age 62.0 ± 14.7; 33 Female and 36 Men; 40 with malignant and 29 with inflammatory lesions) in whom during the endoscopic ultrasound (EUS) of focal pancreatic lesions it was possible to adequately evaluate the flow in the color Doppler, and then perform a biopsy, were qualified for the study. The assessed DTPM parameters flow velocity (TFV), perfusion intensity (TPI), and resistive index (TRI) as well as the following SVFM parameters: flow velocity (FV), volume flow (VolF), and resistive index (RI) differed significantly between the malignant and inflammatory lesions (p < 0.005). TFV and TPI have slightly better discriminatory properties than the corresponding FV and VolF parameters (p < 0.10). Considering the Doppler parameters usually evaluated in a given method, the TPI = 0.009 cm/s (sensitivity 79%, specificity 92%, AUC 0.899, p < 0.001) was significantly better (p = 0.014) in differentiating between inflammatory and malignant pancreatic lesions in comparison to FV = 2.526 cm/s (sensitivity 79%, specificity 70%, AUC 0.731, p < 0.001). Tissue perfusion has better discriminatory properties in the differentiation of solid pancreatic lesions than the Doppler blood flow examination in the single vessel within the tumor.
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JAKs are intracellular protein tyrosine kinases that, through activation of STATs, are responsible for signal transduction pathways that regulate cellular responses to numerous cytokines, growth factors and hormones in many different cells. JAK-STAT signaling plays a key role in regulating immune function, and cytokines - such as IL-23, IL-12 and type I interferons - are central to the pathogenesis of autoimmune diseases, including psoriasis, inflammatory bowel disease and systemic lupus erythematosus. Here the authors review the evidence for targeting TYK2 as a more specific approach to treating these conditions. TYK2 inhibitors are clinically effective in autoimmune and inflammatory diseases and may avoid some of the complications reported with nonselective JAK inhibitors.
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Doenças Autoimunes/tratamento farmacológico , Imunoterapia/métodos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , TYK2 Quinase/antagonistas & inibidores , Doenças Autoimunes/imunologia , Humanos , Doenças Inflamatórias Intestinais/imunologia , Lúpus Eritematoso Sistêmico/imunologiaRESUMO
This paper is an update of the diagnostic and therapeutic recommendations of the National Consultant for Gastroenterology and the Polish Society of Gastroenterology from 2012. It contains 46 recommendations for the diagnosis and treatment, both pharmacological and surgical, of Crohn's disease in adults. The guidelines were developed by a group of experts appointed by the Polish Society of Gastroenterology and the National Consultant in the field of Gastroenterology. The methodology related to the GRADE methodology was used to assess the quality and strength of the available recommendations. The degree of expert support for the proposed statement, assessment of the quality of evidence and the strength of the recommendation was assessed on a 6-point Likert scale. Voting results, quality and strength ratings with comments are included with each statement.
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Isolated macro-aspartate aminotransferase (macro-AST) in asymptomatic adults and children is a benign condition. In patients, however, macro- AST can be associated with neoplasms and autoimmunologic disorders, particularly with gastrointestinal diseases. CASE REPORT: We described a case of persistently elevated serum aspartate aminotransferase in an asymptomatic young woman who was correctly diagnosed with macro-AST after the elevated serum AST was found four years ago. To establish the diagnosis of macro-AST, we used non-invasive and inexpensive polyethylene glycol (PEG) precipitation assay. We advocate more widespread use of this method for routine laboratory diagnosis.
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Hepatopatias , Neoplasias , Adulto , Aspartato Aminotransferases , Criança , Feminino , HumanosRESUMO
Within the last 20 years, tumour necrosis factor inhibitors have been proven to be effective in achieving and maintaining clinical and endoscopic remission in patients with Crohn's disease and ulcerative colitis. Since 2013, when infliximab originator lost its patent protection, patients with inflammatory bowel diseases (IBDs) in Poland have also been treated with biosimilar drugs. Biosimilars are drugs with high similarity to their reference products in terms of physicochemical properties, including structure, safety, and efficacy. Biosimilars are approved for use on the basis of the same rigorous quality standards as their reference products. In 2018, also biosimilars of adalimumab have become available. Studies published to date have shown that biosimilars do not differ from reference drugs in terms of the efficacy and safety. There are numerous data to confirm that a single switch of biological drugs (mainly from reference to biosimilar drugs) has no effect on therapy efficacy and safety. However, a significantly lower cost of therapy with biosimilars not only allows us to treat a much larger number of patients but may also necessitate multiple switches from reference drugs to biosimilars (including biosimilars produced by different manufacturers). Recently, the first results have been published concerning multiple switches in patients with psoriasis and rheumatoid arthritis. However, no such data are currently available for patients with IBDs.
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BACKGROUNDS: Colorectal cancer is the third most common cancer in economically developed countries. Molecular studies and, in particular, gene expression have contributed to advances in the diagnosis and treatment of many cancers. Genes can be molecular and therapeutic markers, but because of the large molecular diversity in colorectal cancer the knowledge is not yet fully established. Probably one of the most crucial processes during early cancer development is inflammation. The inflammatory response in the tumor is an important indicator of molecular etiology and later of cancer progression. OBJECTIVE: The aim of this work is to identify potential biomarkers for early stage of colorectal adenocarcinoma in patients' bowel tissues using transcriptomic analysis. METHODS: Expression of the inflammatory response genes of colorectal cancer at all clinical stages (I-IV) and control of the bowel were evaluated by oligonucleotide microarrays. RESULTS: Based on statistical analysis many differentially expressed genes were selected. LCK (LCK Proto-Oncogene, Src Family Tyrosine Kinase), GNLY (granulysin), SLC6A6 (Solute-Carrier Family 6 Member 6) and LAMP2 (Lysosomal Associated Membrane Protein 2) were specific for the early stage of the disease. These genes had the properties of the good biomarkers. CONCLUSIONS: The expression of LCK, GNLY, SLC6A6 and LAMP2 genes could be valuable potential diagnostic biomarkers of the early stage of colorectal adenocarcinoma.
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Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Perfilação da Expressão Gênica/métodos , Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Proto-Oncogene MasRESUMO
INTRODUCTION In Poland, anti-tumor necrosis factor (TNF) therapy for Crohn disease (CD) is reimbursed in inflammatory disease (CD activity index [CDAI] >300 points) or perianal disease, in cases where conventional treatment has failed. OBJECTIVES We assessed patients receiving TNF inhibitors to establish how limited access to the therapy influences the selection of the population for treatment. PATIENTS AND METHODS Consecutive adult patients with CD starting infliximab or adalimumab in the years 2014 to 2015 were included in the study. Age at symptom onset and diagnosis of CD, disease location and behavior, previous treatment, CDAI, and body mass index (BMI) were evaluated. Subsequently, the age and sex of all patients with CD on antiTNF therapy reimbursed by the Polish National Health Fund were analyzed. RESULTS Among 256 patients, there were 113 women (44.1%) and 143 men (55.9%). The median time from diagnosis to enrollment was longer in women than in men (9 years vs 5.5 years; P = 0.02), and the proportion of women receiving TNF inhibitors for 5 years or less since diagnosis was lower than that of men (42.5% vs 57.7%; P = 0.017). Disease locations, behavior, and CDAI were similar between the groups, while the median BMI was lower in women than in men (20.6 kg/m2 vs 22.6 kg/m2; P = 0.01). In Poland in general, in the years 2010 to 2015, TNF inhibitors for CD were taken by fewer women than men (2208 vs 4789; 46%; 95% confidence interval, 45-48). The median age of treated women was 29 years and that of men-27 years (P <0.001). CONCLUSIONS Compared with their male counterparts, women with CD receive TNF inhibitors less frequently, at an older age, and following a longer disease duration. It is unknown whether this is a regional or more widespread phenomenon.
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Adalimumab/uso terapêutico , Doença de Crohn/tratamento farmacológico , Imunoterapia/estatística & dados numéricos , Infliximab/uso terapêutico , Adulto , Doença de Crohn/terapia , Gerenciamento Clínico , Feminino , Humanos , Masculino , Polônia , Estudos Prospectivos , Sistema de Registros , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologia , Adulto JovemRESUMO
Adalimumab is a subcutaneously administered recombinant fully human monoclonal antibody targeting tumor necrosis factor alpha. It has been approved for use in Poland to treat patients with Crohn's disease under the program of Polish National Health Found since 2010. AIM: The aim of this study was to evaluate the efficacy of adalimumab monotherapy for inducing clinical remission in patients with active Crohn's disease . The primary outcome assessment was the reduction in score to 150 or below on the Crohn's Disease Activity Index (CDAI) at 12 weeks and the secondary one was the reduction in ΔCDAI of at least 100 points. MATERIALS AND METHODS: From January 2011 to December 2015 we treated 68 patients with active Crohn's disease (mean CDAI score 359). All the patients came from region of Silesia, an area with the same environment conditions. The patients were given adalimumab (Humira, AbbVie) subcutaneously at a dose of 160 mg at week 0, 80 mg at week 4 and 40 mg every two weeks thereafter. RESULTS: Twenty eight patients (41%) had a clinical remission at week 12 (CDAI ≤150) and 33 patients (49%) had a ΔCDAI response. During the 12-week of induction therapy infection with Clostridium difficile occurred in 4 patients and one patient died of a severe CMV infection. CONCLUSIONS: Adalimumab is effective as induction therapy for patients with moderate-to-severe Crohn's disease, however in individual cases serious infections including CMV infection can occur. A potential predictive factors for response can be female gender, non-smoking status and high CRP level at baseline.
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Adalimumab/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Doença de Crohn/tratamento farmacológico , Adolescente , Adulto , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Polônia , Indução de Remissão , Resultado do Tratamento , Adulto JovemRESUMO
Chronic diarrhea is a very common problem in the general population. It requires a physician to differentiate its causes and depending on its etiology referring the patient to a hospital for diagnosis and subsequent treatment. One of the causes of chronic diarrhea may be microscopic colitis, which is characterized by the presence of clinical symptoms without endoscopic or radiological abnormalities. Diagnosis is based on a histopathological examination of the colon and thus clinical suspicion of the disease is so important for further diagnosis and treatment, which is primarily based on the use of topical steroids such as budesonide.
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Anti-Inflamatórios/uso terapêutico , Budesonida/uso terapêutico , Colite Microscópica/diagnóstico , Colite Microscópica/tratamento farmacológico , Diarreia/diagnóstico , Diarreia/tratamento farmacológico , Doença Crônica , HumanosRESUMO
Microscopic colitis (MC) is frequent, although still uncommonly diagnosed, cause of chronic diarrhea. The etiopathology of MC is unknown but this disease has strong influence on patient's quality of life (measured by health-related quality of life - HRQoL). MC is characterized by microscopic abnormalities in large bowel's mucosa whereas endoscopic and radiological examination findings are normal. The treatment of MC is an essential social and financial problem due to its frequency in society. Thanks to the results of some controlled research which judged efficiency of some medicines as well as advisory groups recommendations, the MC therapy is nowadays going from empiric to accordance with evidence based medicine.
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Colite Microscópica/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Doença Crônica , Colite Microscópica/complicações , Colite Microscópica/patologia , Diarreia/etiologia , Humanos , Mucosa Intestinal/patologia , Intestino Grosso/efeitos dos fármacos , Intestino Grosso/patologiaRESUMO
UNLABELLED: The carcinogenesis of colorectal cancer involves many factors, which modify the functioning of cells and can include prostaglandins. Resection of tumours and/or radiotherapy provide potentially curative therapy for cancer of the rectum. AIM: The aim of the study was to asses the effects of neoadiuvant teleradiotherapy on PGE2 concentrations in the serum and in the resected bowel tissue as well as on COX-2 gene expression in patients with rectal cancer. MATERIALS AND METHODS: Group I (n=20) included patients with resectable tumour (T1-2,No) treated exclusively by surgery, and group II (n=20) - patients with resectable tumours (T3) and nonresectable ones (T4). All the patients out of group II were put to the surgery after the previous teleradiotherapy applied to them. PGE2 concentrations were examined using the RIA method, while COX-2 mRNA expression was analyzed with the use of the PCR method. RESULTS: PGE2 serum concentrations in the group I prior to the resection did not differ from PGE2 concentrations in the group II prior to the resection (p=0,9488). However, radiation had caused reduction of PGE2 serum concentration prior to the resection in patients from the group II in comparison with the group I (p=0,0115). PGE2 serum concentrations after resection in the group I did not differ significantly from PGE2 concentrations in group II after resection (p=0,4511) (two-factor analysis of variation with interaction, p=0,3117). Radiotherapy did not change significantly PGE2 concentrations in the tumour and margin (two-factor analysis of variations with interaction, p=0,3137). The comparison between the number of patients who showed higher COX-2 mRNA expression in tumour than in the margin in the group I and II, did not reveal differences (p=0,6614). CONCLUSIONS: Neoadiuvant teleradiotherapy decreased PGE2 concentration in the serum, thus showed similar effect as tumour resection.
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Ciclo-Oxigenase 2/sangue , Dinoprostona/sangue , Terapia Neoadjuvante , Radioterapia , Neoplasias Retais/terapia , Humanos , Neoplasias Retais/sangueRESUMO
Over three last decades, it has been noticed that morbidity of immunology-dependent illnesses, like asthma, inflammatory bowel disease or atopic dermatitis, apparently increased. That is the reason to focus on searching and exploring new ideas which could explain etiopathology of those diseases. In etiopathology the role of environmental factors is particularly emphasized. Research indicated the inverse relationship between the frequency of infectious and/ or parasites and autoimmune diseases. It was a leading subject of many studies what allowed to create a hypothesis which explains the phenomenon. The most original and innovative idea, named hygenic hypothesis, was proposed in the late 80s of the last century. Avoiding or limiting the contact with common bacteria and parasites in well-and very well-developed countries probably caused depletion of immune memory which resulted in the hypersensitive response after exposure to general factors. Nowadays, autoimmunological diseases make really serious problem for medical care in the United States of America and Western European countries, ranking just behind cardiovascular diseases, cancer and metabolic sicknesses.
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Higiene , Doenças Inflamatórias Intestinais/etiologia , Humanos , Sistema Imunitário , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/parasitologiaRESUMO
This paper complements the previously published Guidelines of the Working Group of the Polish Society of Gastroenterology and former National Consultant in Gastroenterology regarding the management of patients with Crohn's disease and ulcerative colitis. Attention was focused on the new pharmaceutical recently registered for inflammatory bowel disease treatment.