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1.
Artigo em Inglês | MEDLINE | ID: mdl-34402469

RESUMO

OBJECTIVES: COVID-19 has evolved into a global health crisis, variably affecting the management of patients with chronic illnesses. Patients with inflammatory bowel disease (IBD) may represent a vulnerable population due to frequent administration of immune-modifying treatments. We aimed to depict the natural history of COVID-19 infection in Greek patients with IBD at a nationwide level via unbiased reporting of all cases that were registered during the sequential waves of the pandemic. METHODS: Following a national call from the Hellenic Society for the study of IBD, we enrolled all IBD patients with established diagnoses of COVID-19. Clinical and epidemiological data, including COVID-19 modifying factors and IBD-associated therapies, were analyzed against adverse outcomes (hospitalization, ICU admission and death). RESULTS: We identified 154 IBD patients who were diagnosed with COVID-19 (men: 58.4%; mean age=41.7 years [SD = 14.9]; CD: 64.3%). Adverse outcomes were reported in 34 patients (22.1%), including 3 ICU admissions (1.9%) and two deaths (1.3%). Multivariate logistic regression analysis showed that age (OR = 1.04, 95% CI, 1-1.08) and dyspnea at presentation (OR = 7.36, 95% CI, 1.84-29.46) were associated with worse outcomes of COVID-19 infection. In contrast, treatment with biologics, in particular anti-TNF agents, exerted a protective effect against an unfavorable COVID-19 disease course (OR = 0.4, 95% CI, 0.16-0.99). Patients on subcutaneous biologics were more likely to halt treatment due to the infection as compared to those on intravenous biologics. CONCLUSIONS: IBD patients who developed COVID-19 had a benign course with adverse outcomes being infrequent. Treatment with anti-TNF biologics had a protective effect, thus, supporting continuation of therapy during the pandemic.

2.
Clin J Gastroenterol ; 14(6): 1632-1636, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34453280

RESUMO

Hyperplastic polyps consist a very frequent finding in colonoscopy having a very low potential to malignancy. According to the international guidelines, it is recommended that all polyps should be resected except for diminutive (≤ 5 mm) rectal and rectosigmoid polyps which are predicted with confidence to be hyperplastic. Therefore, in departments where optical diagnosis can be ensured, a "resect and discard" strategy may be implemented for diminutive polyps. In our case, a duodenal-type follicular lymphoma was detected in a 5 mm rectum polyp with hyperplastic appearance. After 4 months, the lymphoma was detected also in stomach and duodenum. Under therapy with Rituximab, she is in remission. To our knowledge, there has never been reported such a case in the literature. Furthermore, it alerts us that we should be very cautious with the optical diagnosis and the "resect and discard strategy".


Assuntos
Pólipos do Colo , Linfoma Folicular , Pólipos do Colo/cirurgia , Colonoscopia , Duodeno , Feminino , Humanos , Linfoma Folicular/diagnóstico , Reto , Estômago
5.
BMC Gastroenterol ; 21(1): 269, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187376

RESUMO

BACKGROUND: Anemia is a common extraintestinal manifestation of Inflammatory Bowel Disease (IBD) affecting negatively the patients' quality of life. The aim of this study was to determine the frequency and real-life management of anemia in IBD patients in Greece. METHODS: This study was conducted in 17 Greek IBD referral centers. Demographic, clinical, laboratory, IBD and anemia treatment data were collected and analyzed retrospectively. RESULTS: A total of 1394 IBD patients [560 ulcerative colitis (UC), 834 Crohn's disease (CD)] were enrolled. Anemia at any time was reported in 687 (49.3%) patients of whom 413 (29.6%) had episodic and 274 (19.7%) had recurrent/persistent anemia. Anemia was diagnosed before IBD in 45 (6.5%), along with IBD in 269 (39.2%) and after IBD in 373 (54.3%) patients. In the multivariate analysis the presence of extraintestinal manifestations (p = 0.0008), IBD duration (p = 0.026), IBD related surgeries and hospitalizations (p = 0.026 and p = 0.004 accordingly) were risk factors of recurrent/persistent anemia. Serum ferritin was measured in 839 (60.2%) IBD patients. Among anemic patients, 535 (77.9%) received treatment. Iron supplementation was administered in 485 (90.6%) patients, oral in 142 (29.3%) and intravenous in 393 (81%). CONCLUSIONS: The frequency of anemia in IBD patients, followed at Greek referral centers, is approximately 50%. Development of recurrent/persistent anemia may be observed in 20% of cases and is independently associated with the presence of extraintestinal manifestations, IBD duration, IBD related surgeries and hospitalizations. Anemia treatment is administered in up to [Formula: see text] of anemia IBD patients with the majority of them receiving iron intravenously.


Assuntos
Anemia , Colite Ulcerativa , Doenças Inflamatórias Intestinais , Anemia/epidemiologia , Anemia/etiologia , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Grécia/epidemiologia , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Qualidade de Vida , Estudos Retrospectivos
6.
Artigo em Inglês | MEDLINE | ID: mdl-34034278

RESUMO

BACKGROUND AND AIMS: This real-world study assessed the impact of golimumab on health-related quality of life (HRQoL) and other patient-reported outcomes (PROs) in patients with ulcerative colitis over 12 months in Greece. METHODS: GO-LIFE was a noninterventional, prospective, multicenter, 12-month study. Patients who had moderately-to-severely active ulcerative colitis were naïve to antitumor necrosis factor (anti-TNFα) therapy and had failed previous conventional therapy. Patients received golimumab as per label. The primary endpoint was patients achieving inflammatory bowel disease questionnaire 32-item (IBDQ-32) remission at 12 months. Secondary endpoints, at 6 and 12 months, included patients achieving IBDQ-32 response; the mean change in the treatment satisfaction questionnaire for medication (TSQM) and the work productivity and activity impairment in ulcerative colitis (WPAI:UC) questionnaires; changes in healthcare utilization; patients achieving clinical response and remission; adherence rates and the percentage of patients who discontinued golimumab. RESULTS: IBDQ-32 remission was achieved by 76.9% of patients at 12 months. Mean changes in all TSQM and WPAI:UC domain scores at 12 months were statistically significant. Clinical remission was achieved by 49.4 and 50.6% of patients at 6 and 12 months, and clinical response by 59.3 and 56.8%, respectively. All patients but one (80/81) had high adherence (≥80%) to golimumab treatment over 12 months. Ulcerative colitis-related health care resource utilization was reduced during the follow-up period. CONCLUSIONS: In real-world settings, treatment with golimumab resulted in meaningful improvements in HRQoL and other PROs, and in disease activity at 6 and 12 months in patients with moderately-to-severely active ulcerative colitis who were naïve to anti-TNFa therapy.

7.
Inflamm Bowel Dis ; 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34042157

RESUMO

BACKGROUND: Improving treatment outcomes with biological therapy is a demanding current need for patients with inflammatory bowel disease. Discovery of pretreatment prognostic indicators of response may facilitate patient selection and increase long-term remission rates. We aimed to identify baseline mucosal gene expression profiles with predictive value for subsequent response to or failure of treatment with the monoclonal antibody against integrin α4ß7, vedolizumab, in patients with active ulcerative colitis (UC). METHODS: Mucosal expression of 84 immunological and inflammatory genes was quantified in RNA extracted from colonic biopsies before vedolizumab commencement and compared between patients with or without response to treatment. Significantly differentiated genes were further validated in a larger patient cohort and within available public data sets, and their functional profiles were studied accordingly. RESULTS: In the discovery cohort, we identified 21 genes with a statistically significant differential expression between 54-week responders and nonresponders to vedolizumab. Our validation study allowed us to recognize a "core" mucosal profile that was preserved in both discovery and validation cohorts and in the public database. The applied functional annotation and analysis revealed candidate dysregulated pathways in nonresponders to vedolizumab, including immune cell trafficking, TNF receptor superfamily members mediating noncanonical NF-kB pathway, in addition to interleukin signaling, MyD88 signaling, and toll-like receptors (TLRs) cascade. CONCLUSIONS: Nonresponse to vedolizumab in UC is associated with specific pretreatment gene-expression mucosal signatures and dysregulation of particular immunological and inflammatory pathways. Baseline mucosal and/or systemic molecular profiling may help in the optimal stratification of patients to receive vedolizumab for active UC.

8.
Dig Dis Sci ; 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33751325

RESUMO

BACKGROUND: Optimization of treatment with biologics is currently an unmet need for patients with ulcerative colitis (UC). Real-world studies provide neutral estimates of drug efficacy and safety within unselected patient populations and allow for the recognition of specific characteristics that affect response to therapy. AIMS: We aimed to depict the efficacy of vedolizumab in patients with UC in a real-world setting and identify prognosticators of improved outcomes. METHODS: Patients with active UC who commenced treatment with vedolizumab were prospectively followed up. Patient-reported outcomes (PROs) and clinical/endoscopic-reported outcomes were recorded at baseline and at weeks 14 and 54. Predefined endpoints of early and persistent efficacy were analyzed against clinical characteristics to identify prognostic factors for response. RESULTS: We included 96 patients (anti-TNF-exposed = 38.5%). At week 14, 73 patients (76%) had clinical response and 54 (56.3%) clinical remission. At week 54, the primary endpoint of vedolizumab persistence was met by 72 patients (75%), whereas steroid-free clinical remission by 59.4%. Among patients who had endoscopy, rates for mucosal healing (Mayo endoscopic score of 0) were 29.8% at week 14 and 44.6% at week 54, respectively. Vedolizumab treatment led to significant improvements in quality of life. Corticosteroid-refractory or anti-TNF-refractory disease, articular manifestations, and high baseline UC-PRO2 were associated with decreased efficacy of vedolizumab in the primary and secondary outcomes. CONCLUSIONS: Vedolizumab is characterized by high efficacy and long-term treatment persistence in UC. More aggressive disease, as indicated by refractoriness to steroids or anti-TNFs and elevated baseline PROs, may predict suboptimal response and help pre-treatment prognostic stratification of patients.

9.
Dig Dis Sci ; 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33515378

RESUMO

BACKGROUND: Misdiagnosed sessile serrated lesions (SSLs) are important precursors for interval colorectal cancers. AIMS: We investigated the usage of acetic acid (AA) solution for improving the detection of SSLs in the right colon in a randomized controlled trial. METHODS: A tandem observation of the right colon was performed in 412 consecutive patients. A first inspection was performed under white light high-definition endoscopy. In the AA group, a low concentration vinegar solution (AA: 0.005%) irrigated by a water pump in the right colon was compared with a plain solution of normal saline (NS) in the diagnostic yield of SSLs during the second inspection. Secondary outcomes in overall polyp detection were measured. RESULTS: Qualitative comparisons showed significant differences in the detection rates of all polyps except adenomas, with remarkable improvement in the demonstration of advanced (> 20 mm), SSLs, and hyperplastic polyps during the second inspection of the right colon using the AA solution. Significant improvement was also noted in the AA group, as far as the mean number of polyps/patient detected, not only in SSLs (AA group: 0.14 vs. NS group: 0.01, P < 0.001), but also in all histological types and all size-categories in the right colon. Small (≤ 9 mm) polyps were detected at a higher rate in the sigmoid colon expanding the effect of the method in the rest of the colon. CONCLUSION: AA-assisted colonoscopy led to a significant increase in SSLs detection rate in the right colon in a safe, quick, and effective manner.

11.
Nutrients ; 12(4)2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32290232

RESUMO

Enteral nutrition seems to play a significant role in the treatment of both adults and children with active Crohn's disease, and to a lesser degree in the treatment of patients with active ulcerative colitis. The inclusion of some special factors in the enteral nutrition formulas might increase the rate of the efficacy. Actually, enteral nutrition enriched in Transforming Growth Factor-ß reduced the activity index and maintained remission in patients with Crohn's disease. In addition, a number of experimental animal studies have shown that colostrum exerts a significantly positive result. Probiotics of a special type and a certain dosage could also reduce the inflammatory process in patients with active ulcerative colitis. Therefore, the addition of these factors in an enteral nutrition formula might increase its effectiveness. Although the use of these formulas is not supported by large clinical trials, it could be argued that their administration in selected cases as an exclusive diet or in combination with the drugs used in patients with inflammatory bowel disease could benefit the patient. In this review, the authors provide an update on the role of enteral nutrition, supplemented with Transforming Growth Factor-ß, colostrum, and probiotics in patients with inflammatory bowel disease.


Assuntos
Colite Ulcerativa/terapia , Colostro , Doença de Crohn/terapia , Suplementos Nutricionais , Nutrição Enteral , Fenômenos Fisiológicos da Nutrição , Probióticos/administração & dosagem , Fator de Crescimento Transformador beta/administração & dosagem , Adulto , Criança , Feminino , Humanos , Masculino , Resultado do Tratamento
12.
Dig Dis ; 38(1): 23-30, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31288225

RESUMO

AIM: To evaluate the uptake of screening colonoscopy among physicians as compared to the general population. METHODS: Asymptomatic physicians, aged 45-67 years, at average risk for colorectal cancer (CRC), working in the participating National Health System hospitals were asked to complete a questionnaire regarding the uptake of screening colonoscopy. The results were compared to those in a background healthy population, aged 50-75 years, inhabitants of a Greek county, who were offered a free access to a screening colonoscopy program for CRC. High-risk adenomas were those ≥10 mm in diameter or any adenoma, regardless of size, with villous histology or high-grade dysplasia. RESULTS: Overall, 267 of 782 physicians and 402 of 6,534 nonphysicians underwent a screening colonoscopy (uptake rates 34.2 and 6.2% respectively, p = 0.00001). Screening colonoscopy has yielded 4 adenocarcinomas (1.6%), 14 high-risk adenomas (5.5%), and 61 low-risk adenomas (25.7%) in the physicians' group. Corresponding figures in the nonphysician arm were 4 (1), 26 (6.5), and 107 (26.6%), respectively. The main reason among physicians for nonadherence was indifference/negligence (n = 213). CONCLUSION: The proportion of physicians undergoing screening colonoscopy for CRC is significantly higher compared to the general population; however, it does remain suboptimal.


Assuntos
Colonoscopia , Programas de Rastreamento , Médicos , Adenoma/diagnóstico , Adenoma/epidemiologia , Idoso , Pólipos do Colo/diagnóstico , Pólipos do Colo/epidemiologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Feminino , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Prevalência
14.
Eur J Gastroenterol Hepatol ; 31(7): 773-776, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30973416

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is an independent risk factor for Clostridium difficile infection (CDI), which is associated significantly with disease severity. We aimed to determine the rates of CDI among hospitalized IBD patients in major tertiary referral hospitals in Greece. PATIENTS AND METHODS: A retrospective analysis was carried out of stool cultures from hospitalized patients investigated for diarrhea, during 2016, tested for CDI with glutamate dehydrogenase (GDH) and toxins A and B. RESULTS: In total, 6932 patients were tested for CDI; 894 were positive for GDH (12.89%) and 339 were also positive for C. difficile toxin (4.89%). The prevalence of CDI among all hospitalized patients was 1.6/1000 patient-days. Among these, there were 401 IBD patients, and 62 were positive for GDH (15.46%) and 30 were also positive for C. difficile toxin (7.48%). The prevalence of CDI in IBD patients was 2.5/1000 patient-days, significantly higher than in non-IBD hospitalized patients (30/401 vs. 309/6531, P=0.013). Among the 30 IBD patients (ulcerative colitis=18, Crohn's disease=12) with CDI, six were receiving biologics, three were on corticosteroids [one combined with azathioprine (AZA) and one combined with 5-ASA], nine were on AZA monotherapy and 12 were on 5-ASA monotherapy. The prevalence of CDI among patients receiving AZA monotherapy was significantly higher than in patients receiving other medications (9/68 vs. 21/333, P=0.047). Mild CDI (n=28) was treated with metronidazole and/or vancomycin, whereas severe CDI (n=2) was treated with vancomycin. CONCLUSION: The prevalence of CDI is higher in hospitalized IBD patients than those without IBD and AZA monotherapy increases the risk of CDI.


Assuntos
Infecções por Clostridium/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Corticosteroides/uso terapêutico , Adulto , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Azatioprina/uso terapêutico , Proteínas de Bactérias/análise , Toxinas Bacterianas/análise , Estudos de Casos e Controles , Diarreia , Enterotoxinas/análise , Fezes/química , Feminino , Glutamato Desidrogenase/análise , Grécia/epidemiologia , Hospitalização , Humanos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Masculino , Mesalamina/uso terapêutico , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
16.
Cancer Genet ; 220: 19-23, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29310834

RESUMO

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder caused by germline mutations in the STK11 tumor suppressor gene. PJS patients face a cumulative cancer risk as high as 93% for all sites combined. The present study reports the spectrum of STK11 mutations in eight families with clinical diagnosis of PJS, summarizes the clinical characteristics of sixteen mutation carriers and launches a National Registry for PJS in Greece. STK11 loss-of-function (LoF) mutations were detected in 87.5% of index patients. Carriers presented with their first manifestation at a median age of 24.9 years, while early-onset breast cancer was the most frequent malignancy observed, highlighting the need for breast surveillance. Out of the deleterious STK11 mutations identified, two were novel: c.375_376delGT and c.676_679dupAACG, with 57.2% of these potentially occurring de novo. Using all available clinical and genetic data, the National Registry for Greek PJS was established in an attempt to better characterize the syndrome and raise awareness among patients and clinicians (available at https://www.peutzjeghersgreece.org). This is the first comprehensive genetic analysis and clinical characterization of Greek PJS patients, where a high incidence of breast cancer was observed and the first attempt to centralize all data in a National Registry.


Assuntos
Testes Genéticos/métodos , Síndrome de Peutz-Jeghers/genética , Adulto , Feminino , Grécia , Humanos , Masculino , Síndrome de Peutz-Jeghers/patologia , Sistema de Registros , Adulto Jovem
17.
Ann Gastroenterol ; 30(6): 622-628, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29118556

RESUMO

Interest in non-coding regions of DNA has been increasing since the mapping of the human genome revealed that human DNA contains far fewer genes encoding proteins than previously expected. However, analysis of the derivatives of DNA transcription (transcriptomics) revealed that the majority of the genetic material is transcribed into non-coding RNA (ncRNA), indicating that these molecules probably provide the functional diversity and complexity of the physiology of the human body that cannot be attributed to the proteins. Of these ncRNA, long ncRNA (lncRNA) have a length greater than 200 nucleotides and share many common components with the coding messenger RNA (mRNA): They are transcribed by RNA polymerase II, comprised of multiple exons and subjected to normal RNA splicing giving RNA products of several kilobases. Scientific data reveal the regulatory role of lncRNA in the control of gene expression during cell development and homeostasis. However, to date, very few lncRNAs have been characterized in depth, and lncRNAs are thought to have a wide range of functions in cellular and developmental processes. These molecules will have the possibility to be used as biomarkers and contribute to the development of targeted therapies. Concerning pancreatic cancer, there are limited data in the literature that correlate the growth of these tumors with deregulation of various lncRNA. We herein review the literature regarding the role of lncRNA as a diagnostic and prognostic biomarker and possible therapeutic target in the neoplasms of the pancreas, particularly pancreatic adenocarcinoma and pancreatic neuroendocrine tumors.

18.
Dig Liver Dis ; 49(10): 1067-1072, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28869157

RESUMO

Inflammatory bowel diseases (IBDs) are multifactorial autoimmune diseases with growing prevalence but the interaction between genetic, environmental and immunologic factors in their development is complex and remains obscure. There is great need to understand their pathogenetic mechanisms and evolve diagnostic and therapeutic tools. Long non-coding RNAs (lncRNAs) are RNA molecules longer than 200 nucleotides that are known to interfere in gene regulation but their roles and functions have not yet been fully understood. While they are widely investigated in cancers, little is known about their contribution in other diseases. There is growing evidence that lncRNAs play critical role in regulation of immune system and that they interfere in the pathogenetic mechanisms of autoimmune diseases, like IBDs. Recent studies have identified lncRNAs in the proximity of IBD-associated genes and single nucleotide polymorphisms within IBD-associated lncRNAs as well. Furthermore, blood samples and pinch biopsies were also analyzed and a plethora of lncRNAs are found to be deregulated in Crohn's disease (CD), Ulcerative colitis (UC) or both. (Especially in UC samples the lncRNAs INFG-AS1 and BC012900 were found to be significantly up-regulated. Similarly, ANRIL, a lncRNA that nest different disease associated SNPs, is significantly down-regulated in inflamed IBD tissue.) This review aims at recording for the first time recent data about lncRNAs found to be deregulated in IBDs and discussing suggestive pathogenetic mechanisms and future use of lncRNAs as biomarkers.


Assuntos
Colite Ulcerativa/genética , Doença de Crohn/genética , RNA Longo não Codificante/genética , Regulação da Expressão Gênica , Loci Gênicos , Humanos , Polimorfismo de Nucleotídeo Único
19.
Dig Dis Sci ; 53(2): 451-60, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17562177

RESUMO

An imbalance between apoptotic and proliferative processes is believed to underlie colorectal neoplasia. We evaluated the expression of bcl-2, p53, mdm2 proteins, and apoptosis in colorectal neoplasms, as well as their correlation with clinico-pathological parameters, using image analysis. Biopsies from 46 colorectal cancers, 121 adenomas, and 25 controls were studied using monoclonal antibodies against p53, bcl-2, mdm2 and the terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) method for apoptosis. P53 and bcl2 protein expression was higher in adenomas >or=1 cm (P < 0.03) and tubulovillous-villous adenomas (P < 0.03), and correlated with dysplasia (P < 0.03). In Cox regression analysis, Dukes' stage was the most significant independent prognostic indicator of a worse survival (P < 0.019), whereas when stage was eliminated, bcl-2 expression was also a powerful predictor for bad prognosis (P = 0.02). In conclusion, both bcl-2 and p53 immunohistochemical profiles may be useful adjuncts in detecting adenomas with a malignant potential, whereas bcl-2 could be used in combination with Dukes' stage as a predictor of prognosis in colorectal cancer.


Assuntos
Adenoma/metabolismo , Apoptose/fisiologia , Neoplasias Colorretais/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Adenoma/patologia , Adulto , Idoso , Neoplasias Colorretais/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Imunofenotipagem , Marcação In Situ das Extremidades Cortadas , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas c-mdm2/metabolismo
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