37 results on '"Coy CSR"'
Search Results
2. ANÁLISE TRANSCRICIONAL TOTAL E ANÁLISE DA EXPRESSÃO DO MIR‐650 NO TECIDO ADIPOSO MESENTERIAL DE PACIENTES COM DOENÇA DE CROHN
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Silva Far, Leal Rf, Pascoal Lb, Ayrizono Mls, Steigleder Km, Torsoni As, Coy Csr, and Simino Lap
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Gastroenterology - Published
- 2019
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3. Correction to: London protocol under water-perfused HRM in a healthy population, towards novel 3D manometric parameters in an evaluation of anorectal functional disorders.
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Anefalos A, Real Martinez CA, and Coy CSR
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- 2024
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4. London Protocol under water-perfused HRM in a healthy population, towards novel 3D manometric parameters in an evaluation of anorectal functional disorders.
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Anefalos A, Martinez CAR, and Coy CSR
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- Humans, Female, Male, Pressure, Reproducibility of Results, London, Manometry methods, Rectum, Anal Canal, Cough, Rectal Diseases diagnosis, Fecal Incontinence
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Background/aim: London Protocol (LP) and Classification allied to high-resolution manometry (HRM) technological evolution has updated and enhanced the diagnostic armamentarium in anorectal disorders. This study aims to evaluate LP reproducibility under water-perfused HRM, provide normal data and new parameters based on 3D and healthy comparison studies under perfusional HRM., Methods: Fifty healthy (25 F) underwent water-perfused 36 channel HRM based on LP at resting, squeeze, cough, push, and rectal sensory. Additional 3D manometric parameters were: pressure-volume (PV) 10
4 mmHg2 .cm (resting, short and long squeeze, cough); highest and lowest pressure asymmetry (resting, short squeeze, and cough). Complementary parameters (CP) were: resting (mean pressure, functional anal canal length); short squeeze (mean and maximum absolute squeeze pressure), endurance (fatigue rate, fatigue rate index, capacity to sustain); cough (anorectal gradient pressure); push (rectum-anal gradient pressure, anal canal relaxation percent); recto-anal inhibitory reflex (anal canal relaxation percent)., Results: No difference to genders: resting (LP, CP, and 3D); short squeeze (highest pressure asymmetry); endurance (CP); cough (CP, highest and lowest pressure asymmetry); push (gradient pressure); rectal sensory. Higher pressure in men: short squeeze (maximum incremental, absolute, and mean pressure, PV, lowest pressure asymmetry); long squeeze (PV); cough (anal canal and rectum maximum pressure, anal canal PV); push (anal canal and rectum maximum pressure). Anal canal relaxation was higher in women (push)., Conclusions: LP reproducibility is feasible under water-perfused HRM, and comparative studies could bring similarity to dataset expansion. Novel 3D parameters need further studies with healthy and larger data to be validated and for disease comparisons., Key Points: • London Protocol and Classification allied with the technological evolution of HRM (software and probes) has refined the diagnostic armamentarium in anorectal disorders. • Novel 3D and deepening the analysis of manometric parameters before the London Classification as a contributory diagnostic tool. • Comparison of healthy volunteers according to the London Protocol under a perfusional high-resolution system could establish equivalence points., (© 2024. The Author(s).)- Published
- 2024
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5. INFLUENCE OF NEOADJUVANT THERAPY ON THE RATIO OF LYMPH NODES.
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Credidio L, Martinez CAR, Magro DO, Carvalho RB, Ayrizono MLS, and Coy CSR
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- Humans, Disease-Free Survival, Lymph Nodes, Rectum, Neoadjuvant Therapy, Rectal Neoplasms therapy
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Background: To evaluate the relationship between the ratio of affected lymph nodes (LNR) and clinical and anatomopathological variables in patients with rectal adenocarcinoma submitted or not to neoadjuvant chemoradiotherapy., Methods: The LNR was determined by dividing the number of compromised LNR by the total number of LNR dissected in the surgical specimen. Patients were divided into two groups: with QRT and without QRT. In each group, the relationship between LNR and the following variables was evaluated: degree of cell differentiation, depth of invasion in the rectal wall, angiolymphatic /perineural invasion, degree of tumor regression and occurrence of metastases. The LNR was evaluated in patients with more than 1, LNR (LNR >12) or less (LNR<12) in the surgical specimen with overall survival (OS) and disease-free survival (DFS). The results were expressed as the mean with the respective standard deviation. Qualitative variables were analyzed using Fisher's exact test, while quantitative variables were analyzed using the Kruskal -Wallis and Mann-Whitney tests. The significance level was 5%., Results: We evaluated 282 patients with QRT and 114 without QRT, between 1995-2011. In the QRT Group, LNR showed a significant association with mucinous tumors (P=0.007) and degree of tumor regression (P=0.003). In both groups, LNR was associated with poorly differentiated tumors (P=0.001, P=0.02), presence of angiolymphatic invasion (P<0.0001 and P=0.01), perineural (P=0.0007, P=0.02), degree of rectal wall invasion (T3>T2; P<0.0001, P=0.02); Compromised LNR (P<0.0001, P<0.01), metastases (P<0.0001, P<0.01). In patients with QRT, LNR<12 was associated with DFS (5.889; 95%CI1.935-19.687; P=0.018) and LNR>12 with DFS and OS (17.984; 95%CI5.931-54.351; P<0.001 and 10.286; 95%CI 2.654-39.854; P=0.007, respectively)., Conclusion: LNR was associated with histological aspects of poor prognosis, regardless of the use of QRT. In the occurrence of less than 12 evaluated LNR, the LNR was associated only with the DFS., Background: • Assessment of the lymph nodes during pathological analysis of the surgical specimen is crucial to determine treatment and prognosis., Background: • Neoadjuvance therapy reduces the number of lymph nodes, being lower than recommended, therefore the lymph node ratio can be an alternative analysis for a better prognosis.
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- 2024
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6. Pharmacological Therapy in Inflammatory Bowel Diseases: A Narrative Review of the Past 90 Years.
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Imbrizi M, Magro F, and Coy CSR
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Inflammatory Bowel Diseases had their first peak in incidence in countries in North America, Europe, and Oceania and are currently experiencing a new acceleration in incidence, especially in Latin America and Asia. Despite technological advances, 90 years after the development of the first molecule for the treatment of IBD, we still do not have drugs that promote disease remission in a generalized way. We carried out a narrative review on therapeutic advances in the treatment of IBD, the mechanisms of action, and the challenges facing the therapeutic goals in the treatment of IBD. Salicylates are still used in the treatment of Ulcerative Colitis. Corticosteroids have an indication restricted to the period of therapeutic induction due to frequent adverse events, while technologies with less systemic action have been developed. Most immunomodulators showed a late onset of action, requiring a differentiated initial strategy to control the disease. New therapeutic perspectives emerged with biological therapy, initially with anti-TNF, followed by anti-integrins and anti-interleukins. Despite the different mechanisms of action, there are similarities between the general rates of effectiveness. These similar results were also evidenced in JAK inhibitors and S1p modulators, the last therapeutic classes approved for the treatment of IBD.
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- 2023
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7. Association of Fibrinolytic Potential and Risk of Mortality in Cancer Patients.
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Gois GSS, Montalvão SAL, Anhaia TRA, Almeida MEA, Martinelli BM, Fernandes MCGL, Hubers SC, Ferreira MRM, Ribeiro DD, Teixeira JC, Carvalheira JBC, Lima CSP, Andreollo NA, Etchebehere M, Zambon L, Ferreira U, Tincani AJ, Martins AS, Coy CSR, Seabra JCT, Mussi RK, Tedeschi H, Anninchino-Bizzacchi JM, and Adventh Cancer Group
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Cancer is a leading cause of death, and the fibrinolytic system shows cooperative effects that facilitate the growth of tumors and the appearance of metastases. This prospective study aimed to evaluate the fibrinolytic potential in cancer patients and its association with mortality outcomes using the fluorometric method of simultaneous thrombin and plasmin generation. The study included 323 cancer patients and 148 healthy individuals. During the 12-month follow-up, 68 patients died. Compared to the control group, cancer patients showed alterations in thrombin production consistent with a hypercoagulability profile, and an increase in plasmin generation. Mortality risk was associated with two parameters of thrombin in both univariate and multivariable analysis: maximum amplitude (Wald 11.78, p < 0.001) and area under the curve (Wald 8.0, p < 0.005), while such associations were not observed for plasmin. In conclusion, this was the first study able to demonstrate the simultaneous evaluation of thrombin and plasmin generation in newly diagnosed untreated cancer patients. Patients with cancer have been observed to exhibit a hypercoagulable profile. During the study, two parameters linked to thrombin generation, MA and AUC, were identified and found to have a potential association with mortality risk. However, no associations were found with parameters related to plasmin generation.
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- 2023
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8. SECOND BRAZILIAN CONSENSUS ON THE MANAGEMENT OF ULCERATIVE COLITIS IN ADULTS: A CONSENSUS OF THE BRAZILIAN ORGANIZATION FOR CROHN'S DISEASE AND COLITIS (GEDIIB).
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Baima JP, Imbrizi M, Andrade AR, Chebli LA, Argollo MC, Queiroz NSF, Azevedo MFC, Vieira A, Costa MHM, Fróes RSB, Penna FGCE, Quaresma AB, Damião AOMC, Moraes ACDS, Santos CHMD, Flores C, Zaltman C, Vilela EG, Morsoletto E, Gonçalves Filho FA, Santana GO, Zabot GP, Parente JML, Sassaki LY, Zerôncio MA, Machado MB, Cassol OS, Kotze PG, Parra RS, Miszputen SJ, Coy CSR, Ambrogini Junior O, Chebli JMF, and Saad-Hossne R
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- Humans, Adult, Brazil, Inflammation, Colitis, Ulcerative drug therapy, Crohn Disease complications, Crohn Disease therapy, Crohn Disease diagnosis, Inflammatory Bowel Diseases complications, Colorectal Neoplasms complications
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Background: Inflammatory bowel diseases are immune-mediated disorders that include Crohn's disease (CD) and ulcerative colitis (UC). UC is a progressive disease that affects the colorectal mucosa causing debilitating symptoms leading to high morbidity and work disability. As a consequence of chronic colonic inflammation, UC is also associated with an increased risk of colorectal cancer., Objective: This consensus aims to provide guidance on the most effective medical management of adult patients with UC., Methods: A consensus statement was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's Disease and Colitis [GEDIIB]). A systematic review including the most recent evidence was conducted to support the recommendations and statements. All recommendations/statements were endorsed using a modified Delphi Panel by the stakeholders/experts in inflammatory bowel disease with at least 80% or greater consensus., Results and Conclusion: The medical recommendations (pharmacological and non-pharmacological) were mapped according to the stage of treatment and severity of the disease onto three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus targeted general practitioners, gastroenterologists and surgeons who manage patients with UC, and supports decision-making processes by health insurance companies, regulatory agencies, health institutional leaders, and administrators.
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- 2023
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9. SECOND BRAZILIAN CONSENSUS ON THE MANAGEMENT OF CROHN'S DISEASE IN ADULTS: A CONSENSUS OF THE BRAZILIAN ORGANIZATION FOR CROHN'S DISEASE AND COLITIS (GEDIIB).
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Imbrizi M, Baima JP, Azevedo MFC, Andrade AR, Queiroz NSF, Chebli JMF, Chebli LA, Argollo MC, Sassaki LY, Parra RS, Quaresma AB, Vieira A, Damião AOMC, Moraes ACDS, Flores C, Zaltman C, Vilela EG, Morsoletto EM, Gonçalves Filho FA, Penna FGCE, Santana GO, Zabot GP, Parente JML, Costa MHM, Zerôncio MA, Machado MB, Cassol OS, Kotze PG, Fróes RSB, Miszputen SJ, Ambrogini Junior O, Saad-Hossne R, and Coy CSR
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- Adult, Humans, Consensus, Brazil, Crohn Disease therapy, Crohn Disease drug therapy, Colitis, Ulcerative drug therapy, Inflammatory Bowel Diseases
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Background: Inflammatory bowel disease (IBD) is an immune-mediated disorder that includes Crohn's disease (CD) and ulcerative colitis. CD is characterized by a transmural intestinal involvement from the mouth to the anus with recurrent and remitting symptoms that can lead to progressive bowel damage and disability over time., Objective: To guide the safest and effective medical treatments of adults with CD., Methods: This consensus was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's disease and Colitis (GEDIIB)). A systematic review of the most recent evidence was conducted to support the recommendations/statements. All included recommendations and statements were endorsed in a modified Delphi panel by the stakeholders and experts in IBD with an agreement of at least 80% or greater consensus rate., Results and Conclusion: The medical recommendations (pharmacological and non-pharmacological interventions) were mapped according to the stage of treatment and severity of the disease in three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus is targeted towards general practitioners, gastroenterologists, and surgeons interested in treating and managing adults with CD and supports the decision-making of health insurance companies, regulatory agencies, and health institutional leaders or administrators.
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- 2023
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10. Adalimumab Serum Concentrations, Clinical and Endoscopic Disease Activity in Crohn's Disease: A Cross-Sectional Multicentric Latin American Study.
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de Souza LR, Magro DO, Teixeira FV, Parra RS, Miranda EF, Féres O, Saad-Hossne R, Soares Prates Herrerias G, Nisihara RM, Coy CSR, Sassaki LY, and Kotze PG
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Despite some variability in ideal serum Adalimumab (ADA) concentrations, there is increasing evidence that higher concentrations of anti-TNF-α agents can be associated with sustained efficacy, and low or undetectable levels may lead to loss of response. This study aims to correlate serum ADA concentrations with clinical and endoscopic activity in patients with Crohn's disease (CD). A cross-sectional and multicentric study was performed with patients with CD, who used ADA for at least 24 weeks. Patients were allocated into groups according to the presence of clinical or endoscopic disease activity. Serum ADA concentrations were measured and compared between groups. Overall, 89 patients were included. A total of 27 patients had clinically active CD and 62 were in clinical remission. Forty patients had endoscopic disease activity and 49 were in endoscopic remission. The mean serum ADA concentration was 10.2 μg/mL in patients with clinically active CD and 14.3 μg/mL in patients in clinical remission ( p = 0.395). The mean serum ADA concentration in patients with endoscopic activity was 11.3 μg/mL as compared to 14.5 μg/mL in those with endoscopic remission ( p = 0.566). There was no difference between serum ADA concentrations regarding clinical or endoscopic activity in CD, as compared to patients in remission.
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- 2023
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11. Pouchitis: insight into the pathogenesis and clinical aspects.
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de Negreiros LMV, Pascoal LB, Genaro LM, Silva JF, Rodrigues BL, Camargo MG, Martinez CAR, Coy CSR, Ayrizono MLS, Fagundes JJ, and Leal RF
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Ulcerative colitis (UC) is a chronic intestinal inflammatory disease and familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease. Both diseases, despite being different, may require the same surgical procedure: proctocolectomy with ileal pouch-anal anastomosis (IPAA). The main complication after this procedure is pouch inflammation (pouchitis). This inflammatory complication can affect up to 60 percent of patients who receive IPAA for UC, and a very small percentage of the FAP patients. The purpose of this review was to determine the current molecular mechanisms in its pathogenesis and detail the risk factors involved in pouchitis, its diagnosis, and treatment., Competing Interests: None., (AJTR Copyright © 2022.)
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- 2022
12. STUDY OF ANORECTAL PHYSIOLOGY PRE AND POS NEOADJUVANT THERAPY FOR RECTAL CANCER BY ANORECTAL MANOMETRY AND JORGE-WEXNER SCORE.
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Fratta CL, Pinheiro LV, Costa FO, Magro DO, Martinez CAR, and Coy CSR
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- Anal Canal, Female, Humans, Male, Manometry, Middle Aged, Rectum, Neoadjuvant Therapy, Rectal Neoplasms pathology, Rectal Neoplasms therapy
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Background: The treatment of distal rectal cancer may be accompanied by evacuation disorders of multifactorial etiology. Neoadjuvant chemoradiotherapy (NCRT) is part of the standard treatment for patients with locally advanced extraperitoneal rectal cancer. The assessment of anorectal function after long-term NCRT in patients with cancer of the extraperitoneal rectum has been poorly evaluated., Objective: The aim of the present study was to evaluate the effects of NCRT on anorectal function and continence in patients with extraperitoneal rectal cancer., Methods: Rectal adenocarcinoma patients undergoing neoadjuvant therapy were submitted to functional evaluation by anorectal manometry and the degree of fecal incontinence using the Jorge-Wexner score, before and eight weeks after NCRT. The manometric parameters evaluated were mean resting anal pressure (ARp), maximum voluntary contraction anal pressure (MaxSp) and average voluntary contraction anal pressure (ASp). All patients underwent the same NCRT protocol based on the application of fluoropyrimidine (5-FU) at a dosage of 350 mg/m2 associated with folic acid at a dosage of 20 mg/m2, intravenously, in the first and last week of treatment, concomitantly with conformational radiotherapy with a total dose of 50.4Gy, divided into 28 daily fractions of 1.8Gy. For statistical analysis of the quantitative variables with normal distribution, the mean, standard deviation, median and interquartile range were calculated. For comparison of two related samples (before and eight weeks after NCRT), Wilcoxon's non-parametric test was used., Results: Forty-eight patients with rectal cancer were included in the study, with a mean age of 62.8 (39-81) years, 36 (75%) of whom were male. The use of NCRT was associated with a decrease in the values of ARp (55.0 mmHg vs 39.1 mmHg, P<0.05) and ASp (161.9 mmHg vs 141.9 mmHg, P<0.05) without changing MaxSp values (185,5 mmHg vs 173 mmHg, P=0.05). There was no worsening of the incontinence score eight weeks after the use of NCRT (3.0 vs 3.3; P>0.05)., Conclusion: NCRT was associated with a reduction in the values of ARp and the ASp. There was no change in MaxSp, as well as in the degree of fecal continence by the Jorge-Wexner score.
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- 2022
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13. Temporal trends in the epidemiology of inflammatory bowel diseases in the public healthcare system in Brazil: A large population-based study.
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Quaresma AB, Damiao AOMC, Coy CSR, Magro DO, Hino AAF, Valverde DA, Panaccione R, Coward SB, Ng SC, Kaplan GG, and Kotze PG
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Background: Population-based data on epidemiology of Inflammatory Bowel Diseases (IBD) in Brazil are scarce. This study aims to define temporal trends of incidence and prevalence rates of Crohn's disease (CD) and ulcerative colitis (UC) in Brazil., Methods: All IBD patients from the public healthcare national system were included from January 2012 to December 2020. Average Annual Percent Change (AAPC) and 95% confidence intervals (CI) were calculated using log-linear regression for incidence and binomial regression for prevalence. Moran's I autocorrelation index was used to analyse clustering of cities by level of prevalence., Findings: A total of 212,026 IBD patients were included. Incidence of IBD rose from 9.4 in 2012 to 9.6 per 100,000 in 2020 (AAPC=0.8%; 95% CI -0.37, 1.99); for UC, incidence increased from 5.7 to 6.9 per 100,000 (AAPC=3.0%; 95% CI 1.51, 4.58) and for CD incidence decreased from 3.7 to 2.7 per 100,000 (AAPC=-3.2%; 95% CI -4.45, -2.02). Prevalence of IBD increased from 30.0 in 2012 to 100.1 per 100,000 in 2020 (AAPC=14.8%; CI 14.78-14.95); for UC, from 15.7 to 56.5 per 100,000 (AAPC=16.0%; CI 15.94, 16.17); for CD from 12.6 to 33.7 per 100,000 (AAPC=12.1% CI 11.95, 12.02). A south-north gradient was observed in 2020 prevalence rates of IBD [I=0.40 (p<0.0001)], CD [I=0.22 (p<0.0001)] and UC [I=0.42 (p<0.0001)]., Interpretation: Incidence of CD is decreasing whereas of UC is increasing, leading to stabilization in the incidence of IBD from 2012 to 2020 in Brazil. Prevalence of IBD has been climbing with 0.1% of Brazilians living with IBD in 2020., Funding: None., Competing Interests: Quaresma AB has received honoraria for speaking from AbbVie, Apsen and Janssen. Aderson OMCD has received honoraria for speaking from AbbVie, Janssen, Pfizer, and Takeda; he has been a consultant for Takeda, AbbVie, and Janssen. Coy CSR has no conflicts of interest. Magro DO has no conflicts of interest. Hino AAF has no conflicts of interest. Valverde DA is CEO of Techtrials a Healthcare Data Science Company. Panaccione R reports consulting from AbbVie, Abbott, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Genentech, Gilead Sciences, Glaxo-Smith Kline, Janssen, Merck, Mylan, Oppilan Pharma, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Satisfai Health, Sandoz, Schering-Plough, Shire, Sublimity Therapeutics, Theravance Biopharma, UCB, and Takeda Pharmaceuticals. He has received speaker's fees from AbbVie, Arena Pharmaceuticals, Celgene, Eli Lilly, Ferring, Gilead Sciences, Janssen, Merck, Pfizer, Roche, Sandoz, Shire, and Takeda Pharmaceuticals. Coward SB has no conflicts of interest. Ng SC has received consulting and speaker fees from AbbVie, Ferring, Janssen, Menarini, and Takeda; served as a Scientific Advisory Board member for AbbVie, Ferring, and Takeda; and received research grants from AbbVie, Ferring, and Janssen. Kaplan GG has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer, Amgen, and Takeda. He has received research support from Ferring, Janssen, AbbVie, GlaxoSmith Kline, Merck, and Shire. He has been a consultant for Gilead. He shares ownership of a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC. UTI Limited Partnership, assignee. Patent WO2019046959A1. PCT/CA2018/051098. 7 Sept. 2018. Kotze PG has received consulting and speaker fees from AbbVie, Janssen, Pfizer, and Takeda. He also received scientific grants from Pfizer and Takeda., (© 2022 The Authors.)
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- 2022
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14. Anti-TNF therapy for ulcerative colitis in Brazil: a comparative real-world national retrospective multicentric study from the Brazilian study group of IBD (GEDIIB).
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Sassaki LY, Magro DO, Saad-Hossne R, Baima JP, Flores C, Correia LM, Celani LMS, De Abreu Ferrari ML, Zacharias P, Feitosa MR, Dos Santos CHM, De Freitas Lins Neto MA, Quaresma AB, De Lima Junior SF, De Vasconcelos GBS, Cassol OS, Dos Santos Pinto A, Kurachi G, Goncalves Filho FA, Gasparini RG, Furlan TK, Catapani WR, Coy CSR, De Souza Menegassi V, Colombo MM, Fróes RSB, Teixeira FV, Moraes AC, Santana GO, Parente JML, Vilela EG, Queiroz NSF, and Kotze PG
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- Adalimumab therapeutic use, Adult, Brazil, Female, Humans, Infliximab adverse effects, Infliximab therapeutic use, Male, Middle Aged, Retrospective Studies, Tumor Necrosis Factor Inhibitors therapeutic use, Colitis, Ulcerative chemically induced, Colitis, Ulcerative drug therapy
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Background: Anti-TNF therapy represented a landmark in medical treatment of ulcerative colitis (UC). There is lack of data on the efficacy and safety of these agents in Brazilian patients. The present study aimed to analyze rates of clinical and endoscopic remission comparatively, between adalimumab (ADA) and infliximab (IFX), in Brazilian patients with UC, and evaluate factors associated with clinical and endoscopic remission after 1 year of treatment., Methods: A national retrospective multicenter study (24 centers) was performed including patients with UC treated with anti-TNF therapy. Outcomes as clinical response and remission, endoscopic remission and secondary loss of response were measured in different time points of the follow-up. Baseline predictive factors of clinical and endoscopic remission at week 52 were evaluated using logistic regression model. Indirect comparisons among groups (ADA and IFX) were performed using Student's t, Pearson χ
2 or Fisher's exact test when appropriated, and Kaplan Meier analysis., Results: Overall, 393 patients were included (ADA, n = 111; IFX, n = 282). The mean age was 41.86 ± 13.60 years, 61.58% were female, most patients had extensive colitis (62.40%) and 19.39% had previous exposure to a biological agent. Overall, clinical remission rate was 66.78%, 71.62% and 82.82% at weeks 8, 26 and 52, respectively. Remission rates were higher in the IFX group at weeks 26 (75.12% vs. 62.65%, p < 0.0001) and 52 (65.24% vs. 51.35%, p < 0.0001) when compared to ADA. According to Kaplan-Meier survival curve loss of response was less frequent in the Infliximab compared to Adalimumab group (p = 0.001). Overall, endoscopic remission was observed in 50% of patients at week 26 and in 65.98% at week 52, with no difference between the groups (p = 0.114). Colectomy was performed in 23 patients (5.99%). Age, non-prior exposure to biological therapy, use of IFX and endoscopic remission at week 26 were associated with clinical remission after 52 weeks. Variables associated with endoscopic remission were non-prior exposure to biological therapy, and clinical and endoscopic remission at week 26., Conclusions: IFX was associated with higher rates of clinical remission after 1 year in comparison to ADA. Non-prior exposure to biological therapy and early response to anti-TNF treatment were associated with higher rates of clinical and endoscopic remission., (© 2022. The Author(s).)- Published
- 2022
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15. Evaluation of different tools for body composition assessment in colorectal cancer - a systematic review.
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Monaco-Ferreira DV, Magro DO, and Coy CSR
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- Body Composition, Cross-Sectional Studies, Humans, Prospective Studies, Retrospective Studies, Colorectal Neoplasms therapy, Hand Strength
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Background: The nutritional status of patients with colorectal cancer (CRC) impacts on treatment response and morbidity. An effective evaluation of the body composition includes the measurements of fat and visceral fat-free mass and is currently being used in the diagnosis of the nutritional status. The better understanding regarding nutritional tools for body composition evaluation in CRC patients may impact on the outcome., Methods: Systematic review conducted according to Preferred Items of Reports for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A literature search was performed using the BVS (LILACS), PubMed, Embase, Cochrane, Scopus, and Web of Science databases., Results: For the initial search, 97 studies were selected and 51 duplicate manuscripts were excluded. Thus, 46 were reviewed and seven studies included with a total of 4,549 patients. Among them were one clinical trial, one prospective study (cohort), two retrospective cohort and two cross-sectional studies. All studies included body composition evaluated by computed tomography, one with bioelectrical impedance, one with handgrip strength, and two employed mid-arm muscle circumference and body mass index., Conclusion: Current evidence suggests that computed tomography has better accuracy in the diagnosis of sarcopenia, visceral fat, and myopenia among individuals with CRC. Further studies are needed to identify cutoff points for these changes aggravated by CRC.
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- 2022
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16. Metagenomics analysis reveals universal signatures of the intestinal microbiota in colorectal cancer, regardless of regional differences.
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Berbert L, Santos A, Magro DO, Guadagnini D, Assalin HB, Lourenço LH, Martinez CAR, Saad MJA, and Coy CSR
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- Humans, Metagenome, Metagenomics, RNA, Ribosomal, 16S genetics, Colorectal Neoplasms pathology, Gastrointestinal Microbiome genetics
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The human gut microbiota is a complex and dynamic community of microorganisms living in our intestines and has emerged as an important factor for colorectal adenocarcinoma (CRC). The purpose of our study was to investigate the microbiota composition in Brazilian CRC patients compared with a local control population (CTL) to find out which changes could be considered universal or regional features in CRC microbiota. Fecal samples were obtained from 28 CRC and 23 CTL individuals. The 16S rRNA gene was used for metagenomic analysis. In addition to the anthropometric variables, the clinical stage (TNM 2018) was considered. Patients with CRC had a significant increase in alpha diversity and a higher percentage of genus Prevotella and a decreased proportion of Megamonas and Ruminococcus. Additionally, the proportion of Faecalibacterium prausnitzii was associated with a better prognosis in the first stages of CRC, and Fusobacterium nucleatum proved to be an important marker of colorectal carcinogenesis and tumor aggressiveness. Although regional differences influence the composition of the microbiota, in the case of CRC, the microhabitat created by the tumor seems to be a major factor. Our results contribute to a better understanding of the carcinogenic process, and even in different environments, some factors appear to be characteristic of the microbiota of patients with CRC.
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- 2022
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17. EXPRESSION OF E-CADHERIN AND CLAUDIN-3 IN THE COLONIC EPITHELIUM AFTER THE INFLIXIMAB THERAPY: EXPERIMENTAL MODEL OF DISUSE COLITIS.
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Alves AJT Jr, Goto EFK, Pereira JA, Domingues FA, Ávila MG, Coy CSR, and Martinez CAR
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- Animals, Cadherins, Claudin-3, Epithelium, Infliximab therapeutic use, Models, Theoretical, Rats, Rats, Wistar, Colitis chemically induced, Colitis drug therapy
- Abstract
Aim: The etiopathogenesis of disuse colitis (DC) has not yet been fully elucidated. The main theories consider that the disease may be related to an increase in anaerobic bacteria, the lack of short-chain fatty acid (SCFA) supply, and immunological disorders that develop in the colorectal segments devoid of fecal transit. The aim of this study was to verify whether the application of infliximab modifies the tissue content of E-cadherin and claudin-3 proteins in colonic epithelium of rats devoid of intestinal transit., Methods: A total of 22 rats underwent intestinal transit bypass using Hartmann's procedure. They remained with the shunt for 12 weeks to allow the development of DC. Later, they were divided into three experimental groups: six animals received 2.0 mL saline solution/week, eight received infliximab at a dose of 5 mg/kg/week, and eight received infliximab at a dose of 10 mg/kg/week for 5 consecutive weeks. At the end of this period, the animals were euthanized, and the colonic segments with and without intestinal transit were removed. DC was diagnosed based on the histological changes defined by a previously validated scale. The tissue expression of E-cadherin and claudin-3 was assessed by immunohistochemistry, and the tissue content of both proteins was quantified by computer-aided image analysis., Results: The colonic segments excluded from fecal transit showed a higher degree of inflammation than those exposed to fecal transit. The degree of inflammation was lower in animals treated with infliximab, regardless of the dose used. The levels of E-cadherin and claudin-3 were reduced in the excluded colon. Treating animals with infliximab increased the levels of both proteins in the colonic segments without intestinal transit, especially in animals receiving a dose of 10 mg/kg/week., Conclusion: Infliximab therapy reduces inflammation in the colonic segments excluded from intestinal transit and increases the tissue content of E-cadherin and claudin-3 proteins, especially when used at a concentration of 10 mg/kg/week.
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- 2022
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18. Myosteatosis Differentially Affects the Prognosis of Non-Metastatic Colon and Rectal Cancer Patients: An Exploratory Study.
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Pozzuto L, Silveira MN, Mendes MCS, Macedo LT, Costa FO, Martinez CAR, Coy CSR, da Cunha Júnior AD, and Carvalheira JBC
- Abstract
Body composition performed by computed tomography (CT) impacts on cancer patients' prognoses and responses to treatment. Myosteatosis has been related to overall survival (OS) and disease-specific survival in colorectal cancer (CRC); however, the independent impact of the association of myosteatosis with prognosis in colon cancer (CC) and rectal cancer (RC) is still unclear. CT was performed at the L3 level to assess body composition features in 227 patients with CRC. Clinical parameters were collected. Overall survival (OS) was the primary outcome, and the secondary outcome was disease-free survival (DFS). Skeletal muscle attenuation and intramuscular adipose tissue area were associated with DFS (p = 0.003 and p = 0.011, respectively) and OS (p < 0.001 and p < 0.001, respectively) in CC patients but not in RC patients. Only the skeletal muscle area was associated with better prognosis related to OS in RC patients (p = 0.009). When CC and RC were analyzed separately, myosteatosis influenced survival negatively in CC patients, worsening DFS survival (hazard ratio [HR], 2.70; 95% confidence interval [CI], 1.07-6.82; p = 0.035) and OS (HR, 5.76; 95% CI, 1.31-25.40; p = 0.021). By contrast, the presence of myosteatosis did not influence DFS (HR, 1.02; 95% CI, 0.52-2.03; p = 0.944) or OS (HR, 0.76; 95% CI, 0.33-1.77; p = 0.529) in RC patients. Our study revealed the interference of myosteatosis in the therapy and survival of patients with CC but not in those with RC, strengthening the value of grouping the two types of cancer in body composition analyses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pozzuto, Silveira, Mendes, Macedo, Costa, Martinez, Coy, da Cunha Júnior and Carvalheira.)
- Published
- 2021
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19. EPIDEMIOLOGICAL PROFILE AND CLINICAL CHARACTERISTICS OF INFLAMMATORY BOWEL DISEASES IN A BRAZILIAN REFERRAL CENTER.
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Fucilini LMP, Genaro LM, Sousa DCE, Coy CSR, Leal RF, and Ayrizono MLS
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- Adult, Brazil epidemiology, Female, Humans, Male, Referral and Consultation, Retrospective Studies, Colitis, Ulcerative epidemiology, Colitis, Ulcerative therapy, Inflammatory Bowel Diseases epidemiology, Inflammatory Bowel Diseases therapy
- Abstract
Background: The increase in the incidence and prevalence rates of inflammatory bowel disease (IBD) is evident in many newly industrialized countries in Asia, Africa, Eastern Europe, and the American continent. In Brazil, records are still scarce, and further studies on this topic are needed., Objective: To evaluate the epidemiological profile and clinical characteristics of patients with IBD who were followed up at a reference service in the state of São Paulo., Methods: We retrospectively analyzed the medical records of patients with IBD who were followed up in a Brazilian Referral Center., Results: A total of 625 patients was evaluated, 416 with Crohn's disease (CD), 190 with ulcerative colitis (UC), and 19 with indeterminate colitis. The average age of the patients was 31.6 years, with a homogeneous distribution between males and females patients. In patients with CD, the most predominant Montreal classification was A2, L3, and B1, with 44.8% of patients presenting with perianal disease; in UC, it was E2, and S0. The main extraintestinal manifestation was rheumatologic, followed by cutaneous and ophthalmic lesions. The majority of patients (85.4%) used some type of medication, the most frequent being aminosalicylates in patients with UC and biological therapy in patients with CD. Regarding surgeries, in CD, a significant percentage of patients underwent some type of surgical procedure, unlike the UC patients, including fistulotomies and placement of seton, derivative ostomies, enterectomy, ileocecectomy/right colectomy, total or partial colectomy, and strictureplasty. Only 195 (31.2%) patients lived in the city of Campinas, while 443 (70.9%) were from the 7th Regional Health Department (RHD), which corresponds to the macro-region of Campinas., Conclusion: In this study, most patients came from the 7th RHD of Campinas; the patients were young, with no predominance of either sex; there was a higher frequency of patients with CD (66.6%). Most of them (85.4%) were undergoing pharmacological treatment, and a significant percentage of CD patients had undergone surgery.
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- 2021
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20. BIOLOGICAL THERAPY PENETRATION FOR INFLAMMATORY BOWEL DISEASE IN LATIN AMERICA: CURRENT STATUS AND FUTURE CHALLENGES.
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Quaresma AB, Coy CSR, Damião AOMC, Kaplan GG, and Kotze PG
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- Biological Therapy, Colitis, Ulcerative drug therapy, Crohn Disease drug therapy, Humans, Latin America, Systematic Reviews as Topic, Inflammatory Bowel Diseases drug therapy, Tumor Necrosis Factor-alpha therapeutic use
- Abstract
Background: The introduction of anti-TNF agents represented a landmark in the management of both Crohn's disease (CD) and ulcerative colitis (UC), with improved efficacy and safety when compared with conventional treatment. However, significant challenges still exist in Latin America to facilitate the access of biological agents for physicians and patients., Objective: The aim of this review was to summarize current evidence on penetration of biological agents for CD and UC in Latin America., Methods: Data are derived from a previous complete systematic review that explored different characteristics of inflammatory bowel diseases (IBD) in Latin America. The studies fully included in this previous systematic review which contained detailed descriptions of the percentage of use of biological agents in different cohorts throughout Latin American and Caribbean countries were included, and descriptive findings were compiled, describing CD and UC penetration of these drugs in different patient cohorts from different countries., Results: From the 61 studies included in the original systematic review, only 19 included data of the percentage of patients treated with biological agents. Anti-TNF use in CD varied from 1.51% in Mexico up to 46.9% in Colombia, with most of the studies describing anti-TNF use in approximately 20%-40% of CD patients. On the other side, the frequency of the use of biologics was clearly lower in UC, varying from 0% in 2009 to up 16.2% in 2018, according to two different Mexican studies. Only two studies described the penetration of anti-TNF agents in IBD overall: 13.4% in a Colombian and 37.93% in a Brazilian study. No studies described percentage of use of new biologic agents (vedolizumab and ustekinumab)., Conclusion: Penetration of anti-TNF agents in Latin America is comparable to the rest of the world in CD, but lower in UC. With the increase in the incidence and prevalence of IBD, specific strategies to increase access to anti-TNF agents in UC and new biological agents overall are warranted.
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- 2019
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21. Remission in Crohn's disease is accompanied by alterations in the gut microbiota and mucins production.
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Magro DO, Santos A, Guadagnini D, de Godoy FM, Silva SHM, Lemos WJF, Vitulo N, Torriani S, Pinheiro LV, Martinez CAR, Saad MJA, and Coy CSR
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- Adult, Bacteria classification, Bacteria genetics, Case-Control Studies, Crohn Disease therapy, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Remission Induction, Young Adult, Bacteria isolation & purification, Crohn Disease microbiology, Dysbiosis prevention & control, Gastrointestinal Microbiome, Mucins metabolism
- Abstract
Previous studies have demonstrated that patients with Crohn's disease (CD) in remission do not exhibit an improvement in gut microbiota composition, which might trigger relapses. The present study investigated the dysbiosis and mucins production in CD patients during remission. We performed an analytical cross-sectional single center study, which recruited 18 CD patients and 18 healthy controls (CG) residing in the same home, meaning that all of the participants experienced the same environmental factors, with similar hygiene status, diet, pollution and other common lifestyle characteristics that may influence the composition of the gut microbiota. When compared to healthy controls, the CD patients exhibited lower microbial α-diversity (p = 0.047), a greater abundance of the Proteobacteria phylum (p = 0.037) and a reduction in the Deltaproteobacteria class (p = 0.0006). There was also a reduction in the Akkermansia (p = 0.002) and Oscillospira (p = 0.024) genera and in the proportion of the yeast Saccharomyces cerevisiae (p = 0.01). Additionally, CD patients in remission presented increased neutral (p = 0.001) and acid mucin (p = 0.002) concentrations. The reductions in the proportions of Oscollospira and Akkermansia genera, sulfate-reducing bacteria and Saccharomyces cerevisiae, observed in the CD group, may account for the increased mucins production observed in these patients.
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- 2019
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22. RELATIONSHIP AMONG PSYCHOLOGICAL WELL-BEING, RESILIENCE AND COPING WITH SOCIAL AND CLINICAL FEATURES IN CROHN'S DISEASE PATIENTS.
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Acciari AS, Leal RF, Coy CSR, Dias CC, and Ayrizono MLS
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- Adolescent, Adult, Female, Humans, Male, Middle Aged, Prospective Studies, Social Support, Socioeconomic Factors, Surveys and Questionnaires, Young Adult, Adaptation, Psychological, Crohn Disease psychology, Quality of Life psychology, Resilience, Psychological
- Abstract
Background: Crohn's disease is chronic, requires prolonged treatment, affects the physical and psychosocial health of patients and may alter their routine, quality of life and well-being. Recent studies recommend monitoring the health of these patients considering physical, psychological and psychosocial aspects, because they are directly related to the disease activity. These studies highlight the relevance of patients' emotional and behavioral conditions and suggest that the identification of the factors that influence the psychological well-being, resilience and Coping in these patients can favor the proper treatment., Objective: To relate psychological well-being, resilience and Coping with social and clinical features of Crohn's disease patients., Methods: Prospective study including 104 patients with Crohn's disease, both genders and mean age of 39 years. Standardized scales were used to assess and to relate psychological well-being, resilience and Coping with social and clinical variables. A questionnaire to characterize the sample and standardized scales in data collection (psychological well-being, resilience pillars and Coping strategies inventory - Folkman & Lazarus) were used. Descriptive analysis of data and statistics for comparison of results were performed., Results: There were significant differences (P<0.05) showing better psychological well-being for male patients, those who without children, were not religious, were employed and were doing complementary activities in addition to clinical treatment. More resilience for the male gender, those who without children, were not religious, divorced, separated or widowed, that received some monthly income; who did not undergo surgery, had the first symptoms after 30 years old and who had complementary activity. There were also significant differences in the use of Coping: usually, women used more developed escape and avoidance strategies; single, married or in stable-union patients used more self-control; not religious used positive revaluation strategy; the ones who were employed showed more self-control and positive reassessment; the ones who had lower family income indicated that they used less the self-control; the ones who had higher family income used more positive re-evaluation; patients who were diagnosed with Crohn's disease between the second decade of life showed to use mores more the positive reassessment strategy than those who were 20 years old or younger., Conclusion: Social aspects influenced psychological well-being, resilience and Coping in patients with Crohn's disease more strongly than clinical aspects. It was possible to identify the profiles with better and worse psychological well-being, resilience and Coping of those who need more support, as well as to know the most used Coping strategies in the studied group.
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- 2019
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23. Reduced Plasma Levels of Very-Long-Chain Dicarboxylic Acid 28:4 in Italian and Brazilian Colorectal Cancer Patient Cohorts.
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Wood PL, Donohue MM, Cebak JE, Beckmann TG, Messias MCF, Credidio L, Coy CSR, Carvalho PO, Crotti S, D'Aronco S, Urso EDL, and Agostini M
- Abstract
Background: There are currently no blood-based biomarkers for early diagnosis of colorectal cancer. Previous research has suggested that very-long-chain dicarboxylic acid (VLCDCA) 28:4 might be such a biomarker., Methods: Using high-resolution mass spectrometry, we analyzed VLCDCA 28:4 in the plasma of colorectal cancer patients in Italian [ n = 62] and Brazilian [ n = 52] cohorts. Additionally, we investigated individuals diagnosed with familial adenomatous polyposis (FAP; n = 27), one of the most important clinical forms of inherited susceptibility to colorectal cancer. Results: Decrements in plasma levels of VLCDCA 28:4 were monitored in colorectal cancer patients. These decreases were independent of the stage of tumor development and the individual's age. However, no decrements in VLCDCA 28:4 were monitored in FAP patients., Conclusions: The plasma levels of VLCDCA 28:4 represent a potential biomarker of sporadic colorectal cancer. In addition, it is possible that resupply of this anti-inflammatory lipid may represent a new therapeutic strategy for CRC and inflammatory disorders.
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- 2018
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24. A Retrospective Analysis of Colorectal Serrated Lesions from 2005 to 2014 in a Single Center: Importance of the Establishment of Diagnostic Patterns.
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Oliveira PSP, Carvalho RB, Magro DO, Camargo MG, Martinez CAR, and Coy CSR
- Abstract
Background: Serrated colorectal lesions are increasingly recognized as an important process in the development of colorectal cancer. Endoscopic and histological diagnosis may be difficult, and knowledge of the serrated lesions is important for the establishment of strategies for treating colorectal lesions. We aimed to analyze serrated lesions diagnosed at a single center and evaluate if there was an increase in their identification over the years., Design and Setting: A retrospective analysis of colonoscopy reports was performed at a specialized center from 2005 to 2014., Methods: Colonoscopy reports about any resected endoscopic lesions were reviewed and subjected to histological diagnosis from 2005 to 2014. Then, serrated lesions were evaluated based on morphological characterization, location, size, occurrence of synchronous lesions, and the patient's history of colorectal cancer and polyps., Results: A total of 2126 colonoscopy examination reports were reviewed, and 3494 lesions were analyzed. On histopathological examination, 1089 (31.2%) were classified as hyperplastic polyps, 22 (0.6%) as sessile serrated adenomas, and 21 (0.6%) as traditional serrated adenomas. There was an increase in the number of cases of sessile and traditional serrated adenomas diagnosed after 2010. Before 2010, two cases of sessile serrated adenomas and seven cases of traditional serrated adenomas were diagnosed; after 2010, 20 cases of sessile serrated adenoma and 14 cases of traditional serrated adenomas were diagnosed., Conclusion: There was an increase in the diagnosis of sessile serrated adenomas over the years, which can be attributed to better accuracy in colonoscopy and histological classification.
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- 2018
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25. Paraestomal hernia with gastric outlet obstruction: a case report and literature review.
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de Andrade VA, Coy CSR, Fagundes JJ, Soares PFDC, Setsuko Ayrizono ML, and Real Martinez CA
- Abstract
An 69-year-old obese woman was submitted to an abdominoperineal resection (APR) with left side end colostomy to treat a synchronic sigmoid and middle rectum cancer. Six months after APR, she develop a PH with a progressive increase of the size. The patient refused the surgical indication. Thirteen years after APR she presenting with abdominal pain, hematemesis, bilious vomiting and non-functioning of the stoma in the last 2 days. She had a distended and painful abdomen without signs of peritoneal irritation and a large incarcerated PH. CT showed a PH with incarcerated gastric herniation. Endoscopy showed a 4 cm ulcerated lesion in the lesser curvature of the stomach whose posteriorly histopathological study revealed that it was an ischemic ulcer. She was submitted a correction of PH using an onlay polypropylene mesh put around of the previous stoma. The patient has an uneventful recovery and was discharged 3 days later.
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- 2018
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26. Long Time from Diagnosis to Surgery May Increase Postoperative Complication Rates in Elective CD Intestinal Resections: An Observational Study.
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Kotze PG, Magro DO, Martinez CAR, Spinelli A, Yamamoto T, Warusavitarne J, and Coy CSR
- Abstract
Background: There is lack of data analyzing short-term postoperative complications and time from diagnosis to surgery in Crohn's disease (CD)., Aim: To compare complication rates after elective abdominal operations in CD patients with different durations of disease., Methods: Retrospective observational study with CD patients who submitted to elective intestinal resections. Patients were allocated in 2 groups according to time to surgery (TS) in less or more than 5 years. Short-term postoperative complications were analyzed and compared between the 2 groups, and binary logistic regression analysis was performed to check for significant variables., Results: 123 patients were finally included, 77 with TS > 5 years (62.6%) and 46 with TS < 5 years (37.4%). Patients with TS > 5 years had higher rates of overall surgical complications ( p = 0.011), reoperations ( p = 0.003), surgical site infections ( p = 0.014), anastomotic dehiscence ( p = 0.021), abdominal abscesses ( p = 0.021), and overall medical complications ( p = 0.019). On logistic regression, the single significant variable was the confection of stomas (OR: 3.203; 95% CI: 1.011-10.151; p = 0.048)., Conclusions: Patients with longer time to surgery showed a significant increase in overall medical and surgical postoperative early complications after elective intestinal resections.
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- 2018
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27. VISCERAL FAT IS INCREASED IN INDIVIDUALS WITH CROHN'S DISEASE: A COMPARATIVE ANALYSIS WITH HEALTHY CONTROLS.
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Magro DO, Barreto MRL, Cazzo E, Camargo MG, Kotze PG, and Coy CSR
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- Adolescent, Adult, Body Mass Index, Case-Control Studies, Cross-Sectional Studies, Female, Humans, Male, Obesity physiopathology, Young Adult, Body Composition physiology, Crohn Disease complications, Intra-Abdominal Fat, Nutritional Status physiology, Obesity etiology
- Abstract
Background: It is known that obesity is associated with a chronic inflammatory state, but few studies have evaluated visceral fat (VF) content and its role in individuals with Crohn's disease (CD)., Objetive: To compare the nutritional status, body composition and proportion of VF between CD individuals and healthy volunteers., Methods: Cross-sectional study that enrolled individuals with Crohn's disease and healthy controls. The stratification according to nutritional status was carried out by means of BMI. The percentage of body fat percentage (%BF) and VF were estimated by means of DEXA. VF proportion was evaluated by means of the VF/BMI and VF/%BF ratios., Results: A total of 78 individuals were included. The control group was comprised of 28 healthy subjects aged 35.39±10 years old (60.7% women); mean BMI=23.94±3.34 kg/m2; mean VF=511.82±448.68 g; mean CRP=0.81±1.78 ng/mL. The CD group was comprised of 50 patients; 11 (22%) were underweight (BMI=18.20±1.97 kg/ m2; %BF=24.46±10.01; VF=217.18±218.95 g; CRP=4.12±4.84 ng/mL); 18 (36%) presented normal weight (BMI=22.43±1.48 kg/m2; %BF=30.92±6.63; VF=542.00±425.47 g and CRP=4.40±1.78 ng/mL); 21 (42%) were overweight or obese (BMI=29.48±3.78 kg/m2; %BF=39.91±7.33; VF=1525.23±672.7 g and CRP=1.33±2.06 ng/mL). The VF/BMI ratio was higher in the CD group when compared to controls (32.41±24.63 vs 20.01±16.23 g per BMI point; P=0.02). Likewise, the VF/%BF was also higher in the CD group (35.21±23.33 vs 15.60±12.55 g per percentage point; P<0.001)., Conclusion: Among individuals with Crohn's disease, BMI presents a direct correlation with visceral fat content. These results indicate the presence of an adiposopathy in Crohn's disease subjects, which is evidenced by a higher visceral fat.
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- 2018
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28. SERUM INFLIXIMAB MEASUREMENT IN INFLAMMATORY BOWEL DISEASE PATIENTS IN REMISSION: A COMPARATIVE ANALYSIS OF TWO DIFFERENT METHODS IN A MULTICENTRIC BRAZILIAN COHORT.
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Teixeira FV, Sassaki LY, Saad-Hossne R, Baima JP, Magro DO, Coy CSR, and Kotze PG
- Subjects
- Adult, Age of Onset, Antibodies blood, Biomarkers blood, Cohort Studies, Cross-Sectional Studies, Drug Monitoring, Female, Humans, Male, Middle Aged, ROC Curve, Tumor Necrosis Factor-alpha antagonists & inhibitors, Young Adult, Colitis, Ulcerative blood, Crohn Disease blood, Enzyme-Linked Immunosorbent Assay, Gastrointestinal Agents blood, Infliximab blood
- Abstract
Background: Infliximab (IFX) therapeutic drug monitoring is an important tool to guide therapeutic decision in inflammatory bowel disease patients. Currently, there are two methods to measure trough levels of IFX, ELISA assays or rapid tests. Despite that the ELISA assay is the most used method in therapeutic drug monitoring, the results take long to be available for clinical use, and it needs to be performed by trained personnel. In contrary, the results of a rapid test take 20 to 30 minutes to be available and can be performed by non-trained lab personnel., Objective: The aim of the study was to compare a rapid test (QB-IFX) for quantitative determination of IFX level to one ELISA assay in a cohort of inflammatory bowel disease patients., Methods: Cross-sectional multicentric study with 49 inflammatory bowel disease patients on maintenance therapy with IFX. Blood samples for IFX serum levels were collected immediately before infusion. IFX serum levels were classified as undetectable, low (<3.0 μg/mL), adequate (3.1-7.0 μg/mL) or high (>7.1 μg/mL). A sensitivity and specificity of each test and a comparison between tests was based on ROC curves., Results: Thirty-four Crohn's disease patients and 15 ulcerative colitis patients in clinical remission were evaluated. The majority of patients had low or adequate serum levels of IFX. In relation to the serum levels proportions with the two methods, there was no significant difference (P=0.84). The ROC analysis identified a concentration threshold >2.9 μg/mL with the QB-IFX test (area under the ROC, 0.82; P<0.0001, sensitivity, 100%; specificity, 61.9%), and >3.83 μg/mL using the ELISA assay (area under the ROC, 0.96; P<0.0001, sensitivity, 100%; specificity, 92.9%)., Conclusion: QB-IFX and ELISA assays to measure IFX levels were comparable. Both methods had accurate sensitivity and specificity to detect undetectable, low and adequate levels, but had showed low specificity for supra therapeutic levels of IFX.
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- 2018
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29. Ileal pouch of ulcerative colitis and familial adenomatous polyposis patients exhibit modulation of autophagy markers.
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Paiva NM, Pascoal LB, Negreiros LMV, Portovedo M, Coope A, Ayrizono MLS, Coy CSR, Milanski M, and Leal RF
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- Adult, Aged, Autophagy-Related Protein 5 metabolism, Biomarkers metabolism, Colonic Pouches pathology, Female, Humans, Male, Microtubule-Associated Proteins metabolism, Middle Aged, Proctocolectomy, Restorative adverse effects, Proctocolectomy, Restorative methods, RNA-Binding Proteins metabolism, Adenomatous Polyposis Coli metabolism, Autophagy, Colitis, Ulcerative metabolism, Intestinal Mucosa metabolism, Pouchitis metabolism
- Abstract
Total retocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgery of choice for patients with ulcerative colitis (UC) that are refractory to clinical treatment. Pouchitis is one of the most common complications after this procedure. Defects in autophagy have been reported in inflammatory bowel diseases. However, there are no studies on the IP. Therefore, we studied markers for autophagy in the IP mucosa of UC and FAP patients comparing them to controls with a normal distal ileum. Sixteen patients with IP in "J" shape, asymptomatic and with endoscopically normal IP were evaluated. The control group consisted of eight patients with normal colonoscopy. There was a significant decrease in the transcriptional levels of ATG5, MAP1LC3A and BAX in the FAP group. There was also a decrease in the protein level of Beclin-1 in the UC and FAP compared to the control group. Although the LC3II levels by immunoblot were higher in the UC group, LC3/p62 co-localization were lower in the immunofluorescence analysis in the UC and FAP compared to the control group. Corroborating these results, there was an increase of p62 by immunoblot in the UC group. These findings indicated a modulation of macroautophagy markers in the IP, which may explain the mucosa inflammation predisposition.
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- 2018
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30. Glucose Metabolism Parameters and Post-Prandial GLP-1 and GLP-2 Release Largely Vary in Several Distinct Situations: a Controlled Comparison Among Individuals with Crohn's Disease and Individuals with Obesity Before and After Bariatric Surgery.
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Magro DO, Cazzo E, Kotze PG, Vasques ACJ, Martinez CAR, Chaim EA, Geloneze B, Pareja JC, and Coy CSR
- Subjects
- Adult, Case-Control Studies, Crohn Disease blood, Cross-Sectional Studies, Female, Glucose Tolerance Test, Humans, Insulin metabolism, Male, Middle Aged, Obesity, Morbid blood, Postoperative Period, Postprandial Period physiology, Preoperative Period, Young Adult, Bariatric Surgery, Blood Glucose metabolism, Crohn Disease metabolism, Glucagon-Like Peptide 1 metabolism, Glucagon-Like Peptide 2 metabolism, Obesity, Morbid metabolism, Obesity, Morbid surgery
- Abstract
Background: This study aims to compare the post-prandial curves of glucose, insulin, GLP-1, and GLP-2 among individuals with Crohn's disease (CD), obese individuals before and after bariatric surgery, and healthy controls., Methods: This an exploratory cross-sectional study that involved five groups of patients (two groups of individuals with CD-active and inactive), bariatric patients (pre- and post-surgery, who were their own controls), and a distinct separated control group of healthy volunteers. C-reactive protein (CRP) levels and the post-prandial curves of glucose, insulin, GLP-1, and GLP-2 curves were assessed and compared., Results: The pre-RYGB group presented significantly higher levels of CRP than the post-RYGB (p = 0.001) and the control group (p = 0.001). The inactive CD group presented a higher post-prandial GLP-1 area under the curve (AUC) than the pre-RYGB group (p = 0.009). The post-RYGB group presented significantly higher AUCs of GLP-2 than the pre-RYGB group (p < 0.0001), both inactive and active CD groups (p < 0.0001 in both situations), and the control group (p = 0.002). The pre-RYGB group presented a significantly higher AUC of glucose than the post-RYGB (p = 0.02) and both active and inactive CD groups (p = 0.019 and p = 0.046, respectively). The pre-RYGB group presented a significantly higher AUC of insulin than the control (p = 0.005) and both CD groups (p < 0.0001)., Conclusions: Obesity is associated with an inflammatory state comparable to the one observed in CD; inflammation may also be enrolled in the blockade of GLP-2. CD individuals present a more incretin-driven pattern of glucose metabolism, as a way to prevent hypoglycemia and compensate the carbohydrate malabsorption and GLP-2 blockade.
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- 2018
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31. Glucagon-Like Peptides 1 and 2 Are Involved in Satiety Modulation After Modified Biliopancreatic Diversion: Results of a Pilot Study.
- Author
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Cazzo E, Pareja JC, Chaim EA, Coy CSR, and Magro DO
- Subjects
- Adult, Appetite Regulation physiology, Biliopancreatic Diversion adverse effects, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 complications, Female, Follow-Up Studies, Glucagon-Like Peptide 1 physiology, Glucagon-Like Peptide 2 physiology, Humans, Male, Middle Aged, Obesity, Morbid blood, Obesity, Morbid complications, Pilot Projects, Postoperative Period, Postprandial Period physiology, Biliopancreatic Diversion methods, Diabetes Mellitus, Type 2 surgery, Glucagon-Like Peptide 1 blood, Glucagon-Like Peptide 2 blood, Obesity, Morbid surgery, Satiation physiology
- Abstract
Background: This paper aimed to evaluate the influence of modified biliopancreatic diversion (BPD) on the levels of GLP-1 and GLP-2 and correlate them with satiety regulation., Methods: This is a pilot prospective cohort study that evaluated six mildly obese individuals with type 2 diabetes mellitus, which underwent modified BPD and were followed-up for 12 months. Levels of GLP-1 and GLP-2 after a standard meal tolerance test were determined and correlated with satiety scores obtained by means of a visual analogue scale (VAS)., Results: There were significant changes in BMI (33 ± 2.2 versus 26.3 ± 2.2 kg/m
2 ; p < 0.001), HbA1c (7.9 ± 1.6 versus 5.8 ± 1.2%; p = 0.026), total cholesterol (172.3 ± 11.1 versus 134.7 ± 16.1 mg/dL; p < 0.001), LDL-c (103.3 ± 13 versus 64.6 ± 12.2 mg/dL; p < 0.001), and postprandial GLP-2 (972.7 ± 326.2 versus 1993.2 ± 1024.7; p = 0. 044). None of the scores obtained in the VAS significantly changed after surgery. After surgery, there were significant correlations of VAS scores and GLP-1 levels in question 01 ("how hungry do you feel?"; R = -0.928; p = .008) and GLP-2 levels in questions 02 ("how full do you feel?" R = 0.943; p = 0.005) and 04 ("how much do you think you can eat now? R = -0.829; p = 0.042)., Conclusions: Modified BPD does not lead to significant changes in satiety evaluated by the VAS; different aspects of satiety regulation are correlated with the postprandial levels of GLP-1 (hunger feeling) and GLP-2 (satiation feeling and desire to eat) 1 year after modified BPD, signaling a specific postoperative gut hormone-related modulation of appetite.- Published
- 2018
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32. COMPARISON OF THE LEVELS OF C-REACTIVE PROTEIN, GLP-1 AND GLP-2 AMONG INDIVIDUALS WITH DIABETES, MORBID OBESITY AND HEALTHY CONTROLS: AN EXPLORATORY STUDY.
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Cazzo E, Pareja JC, Chaim EA, Coy CSR, and Magro DO
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- Adolescent, Adult, Aged, Body Mass Index, Case-Control Studies, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Postprandial Period, Young Adult, Blood Glucose analysis, C-Reactive Protein analysis, Diabetes Mellitus, Type 2 blood, Glucagon-Like Peptide 1 blood, Glucagon-Like Peptide 2 blood, Insulin blood, Obesity, Morbid blood
- Abstract
Background: The glucagon-like peptides 1 and 2 (GLP-1/GLP-2) are gut hormones that may directly affect the glucose homeostasis and their activity seems to be significantly affected by chronic inflammation., Objective: To evaluate the postprandial levels of glucagon-like peptides 1 and 2 (GLP-1/GLP-2), C-reactive protein (CRP), and the postprandial glucose and insulin levels among individuals with obesity, type 2 diabetes, and healthy controls., Methods: An exploratory cross-sectional study, which involved individuals awaiting for bariatric/metabolic surgery and healthy controls. Postprandial levels of GLP-1, GLP-2, glucose, and insulin were obtained after a standard meal tolerance test. Inflammation was assessed by means of CRP., Results: There were 30 individuals enrolled in the study, divided into three groups: non-diabetic with morbid obesity (NDO; n=11 individuals), diabetic with mild obesity (T2D; n=12 individuals), and healthy controls (C; n=7 individuals). The mean CRP levels were significantly higher in the NDO group (6.6±4.7 mg/dL) than in the T2D (3.3±2.2 mg/dL) and C groups (2.5±3.2 mg/dL) (P=0.038). The GLP-1 levels following standard meal tolerance test and the area under the curve of GLP-1 did not differ among the three groups. The GLP-2 levels were significantly lower in the NDO and T2D than in the C group following standard meal tolerance test at all the times evaluated. The area under the curve of the GLP-2 was significantly lower in the NDO and T2D groups than in the C group (P=0.05 and P=0.01, respectively)., Conclusion: GLP-2 levels were impaired in the individuals with obesity and diabetes. This mechanism seems to be enrolled in preventing the worsening of the glucose homeostasis in these individuals.
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- 2018
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33. Comparison of time until elective intestinal resection regarding previous anti-tumor necrosis factor exposure: a Brazilian study on patients with Crohn's disease.
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Kotze PG, Magro DO, Saab B, Saab MP, Pinheiro LV, Olandoski M, Ayrizono MLS, Martinez CAR, and Coy CSR
- Abstract
Background/aims: The use of anti-tumor necrosis factor (anti-TNF) agents seems to reduce surgical rates and delay surgical procedures in prospective trials and population-based studies in the management of Crohn's disease (CD). This study aimed to identify whether preoperative anti-TNF agents influence the time from diagnosis to surgery., Methods: An observational retrospective cohort study was conducted on patients with CD submitted to intestinal resections due to complications or medical therapy failure in a period of 7 years. The patients were allocated into 2 groups according to their previous exposure to anti-TNF agents in the preoperative period. Epidemiological aspects regarding age at diagnosis, smoking, perianal disease, and preoperative conventional therapy were considered. A Kaplan-Meier survival analysis was used to outline possible differences between the groups regarding the time to surgery., Results: A total of 123 patients were included (71 and 52 with and without previous exposure to biologics, respectively). The overall time to surgery was 108±6.9 months (maximum, 276 months). The survival estimation revealed no difference in the mean time to intestinal resection between the groups (99.78±10.62 months in the patients without and 114.01±9.07 months in those with previous anti-TNF use) (log-rank P =0.35). There was no significant difference in the time to surgery regarding perianal CD ( P =0.49), smoking ( P =0.63), preoperative azathioprine ( P =0.073) and steroid use ( P =0.58)., Conclusions: The time from diagnosis to surgery was not influenced by the preoperative use of anti-TNF therapy in this cohort of patients., Competing Interests: CONFLICT OF INTEREST: P.G.K. is a speaker and consultant for Abbvie, Ferring, Janssen, Pfizer and Takeda. All other authors have no financial disclosure.
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- 2018
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34. Usefulness of Transcriptional Blood Biomarkers as a Non-invasive Surrogate Marker of Mucosal Healing and Endoscopic Response in Ulcerative Colitis.
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Planell N, Masamunt MC, Leal RF, Rodríguez L, Esteller M, Lozano JJ, Ramírez A, Ayrizono MLS, Coy CSR, Alfaro I, Ordás I, Visvanathan S, Ricart E, Guardiola J, Panés J, and Salas A
- Subjects
- Adult, Biomarkers blood, Colitis, Ulcerative diagnosis, Colitis, Ulcerative pathology, Colon pathology, Colonoscopy, Female, Humans, Intestinal Mucosa pathology, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Real-Time Polymerase Chain Reaction, Treatment Outcome, Colitis, Ulcerative blood
- Abstract
Background and Aims: Ulcerative colitis [UC] is a chronic inflammatory disease of the colon. Colonoscopy remains the gold standard for evaluating disease activity, as clinical symptoms are not sufficiently accurate. The aim of this study is to identify new accurate non-invasive biomarkers based on whole-blood transcriptomics that can predict mucosal lesions and response to treatment in UC patients., Methods: Whole-blood samples were collected for a total of 152 UC patients at endoscopy. Blood RNA from 25 UC individuals and 20 controls was analysed using microarrays. Genes that correlated with endoscopic activity were validated using real-time polymerase chain reaction in an independent group of 111 UC patients, and a prediction model for mucosal lesions was evaluated. Responsiveness to treatment was assessed in a longitudinal cohort of 16 UC patients who started anti-tumour necrosis factor [TNF] therapy and were followed up for 14 weeks., Results: Microarray analysis identified 122 genes significantly altered in the blood of endoscopically active UC patients. A significant correlation with the degree of endoscopic activity was observed in several genes, including HP, CD177, GPR84, and S100A12. Using HP as a predictor of endoscopic disease activity, an accuracy of 67.3% was observed, compared with 52.4%, 45.2%, and 30.3% for C-reactive protein, erythrocyte sedimentation rate, and platelet count, respectively. Finally, at 14 weeks of treatment, response to anti-TNF therapy induced alterations in blood HP, CD177, GPR84, and S100A12 transcripts that correlated with changes in endoscopic activity., Conclusions: Transcriptional changes in UC patients are sensitive to endoscopic improvement and appear to be an effective tool to monitor patients over time., (© European Crohn’s and Colitis Organisation (ECCO) 2017.)
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- 2017
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35. Adalimumab and postoperative complications of elective intestinal resections in Crohn's disease: a propensity score case-matched study.
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Kotze PG, Magro DO, Martinez CAR, Saab B, Saab MP, Pinheiro LV, Olandoski M, Yamamoto T, and Coy CSR
- Abstract
Background: data are scarce regarding the effect of preoperative Adalimumab (ADA) in postoperative complications in Crohn's disease (CD) patients., Aim: to compare the rates of postoperative complications after intestinal resections in CD, with and without previous exposure to ADA., Method: case-matched retrospective observational study of patients submitted to intestinal resections for CD. The patients were allocated to 2 groups, according to their previous exposure to ADA before surgery. The patients under ADA therapy were matched with controls (patients without previous biologics) with the propensity score method (PSM), according to age at surgery, CD location (Montreal L) and phenotype (Montreal B). Medical and surgical complications were compared., Results: 123 patients were initially considered, 71 with previous biologics (32 under ADA therapy) and 52 without. The PSM selected 25 ADA patients to be matched with 25 controls from the non-biologics group. There was no difference regarding overall surgical complications (40% in the control vs 36% in the ADA group; p = 1.0000) or medical complications (36% vs 12% in the control and ADA groups, respectively; p = 0.095). In univariate analysis, previous ADA was not considered a risk factor for higher postoperative complication rates. Stomas were considered a risk factor for surgical complications, and previous steroids were associated to higher medical complication rates., Conclusions: preoperative ADA did not influence the rates of medical and surgical complications after elective intestinal resections for CD. This was the first study to include exclusively patients under ADA therapy. This article is protected by copyright. All rights reserved., (This article is protected by copyright. All rights reserved.)
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- 2017
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36. Changes in serum levels of lipopolysaccharides and CD26 in patients with Crohn's disease.
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Magro DO, Kotze PG, Martinez CAR, Camargo MG, Guadagnini D, Calixto AR, Vasques ACJ, Ayrizono MLS, Geloneze B, Pareja JC, Saad MJ, and Coy CSR
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Background/aims: Lipopolysaccharide (LPS) is a molecule formed by lipids and polysaccharides and is the major cell wall component of gram-negative bacteria. High LPS levels are known to block CD26 expression by activating Toll-like receptor 4. The aim of this study was to correlate the serum levels of LPS and CD26 in Crohn's disease (CD) patients with serum levels of C-reactive protein (CRP), interleukins, CD activity index, and tumor necrosis factor-α (TNF-α)., Methods: Serum samples were collected from 27 individuals (10 with active CD, 10 with inactive CD, and 7 controls) and the levels of LPS, CD26, TNF-α, interleukin-1β (IL-1β), IL-6, IL-17, and CRP were determined by enzyme-linked immunosorbent assay. The levels of LPS and CD26 were then tested for correlation with TNF-α, IL-1β, IL-6, IL-17, and CRP., Results: Serum levels of LPS were significantly elevated in the active CD group ( P =0.003). Levels of IL-1β ( P =0.002), IL-6 ( P =0.003), and IL-17 ( P <0.001) were lower in the CD groups. Serum TNF-α levels were increased in the active CD group. The CRP levels were elevated in the CD groups when compared to controls ( P <0.001). The CD26 levels were lower in the CD groups than in the control group ( P <0.001). Among the variables analyzed, there was a correlation between LPS and CRP (r=-0.53, P =0.016) in the CD groups., Conclusions: Individuals with CD exhibited higher serum levels of LPS varying from a 2- to 6-fold increase depending on disease activity, when compared with healthy controls. CD26 levels were lower in the CD groups. Both LPS and CD26 correlated with disease severity and serve as potential CD biomarkers., Competing Interests: Conflict of interest: Paulo Gustavo Kotze is a speaker and consultant for Abbvie, Ferring, Janssen, and Takeda.
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- 2017
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37. TISSUE EXPRESION OF THE GENES MUTYH AND OGG1 IN PATIENTS WITH SPORADIC COLORECTAL CANCER.
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Nascimento EFR, Ribeiro ML, Magro DO, Carvalho J, Kanno DT, Martinez CAR, and Coy CSR
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- Adult, Aged, Female, Humans, Male, Middle Aged, Prospective Studies, Adenocarcinoma genetics, Colorectal Neoplasms genetics, DNA Glycosylases genetics, Gene Expression Regulation, Neoplastic
- Abstract
Background: MTUYH and OGG1 genes have importance in the base excision repair systems of oxidized DNA bases. Modification of the tissue expression of these genes is related to the increased risk of developing colorectal cancer., Aim: To evaluate the tissue expression of MUTYH and OGG1 comparing normal and neoplastic tissues of patients with sporadic colorectal cancer and to correlate it with clinical and histopathological variables., Method: MUTYH and OGG1 tissue expression was quantified by RT-PCR in patients with colorectal cancer and the values were compared in normal and neoplastic tissues. MUTYH and OGG1 expression was measured and normalized to the constitutive 18S gene. The level of expression of both genes was correlated with the variables: age, gender, tumor location, size of the tumor, histological type, degree of cell differentiation, invasion depth in the intestinal wall, angiolymphatic infiltration, lymph node involvement and TNM staging., Results: Was found downregulation of both genes in neoplastic when compared to normal tissue. There was downregulation of the MUTYH in larger tumors and in patients with angiolymphatic invasion. Tumors with more advanced TNM stages (III and IV) presented downregulation of both genes when compared to those with earlier stages (I and II)., Conclusion: The MUTYH and OGG1 genes present downregulation in the more advanced stages of colorectal cancer.
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- 2017
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