New insights on the surgical management of ulcerative colitis in the 21st century.

Despite substantial advances in medical therapy since 2005 that have led to the approval and increased use of novel biological agents and small molecules, colectomy is still a therapeutic option for some patients with ulcerative colitis. In the biological era (ie, after the approval of biological agents for ulcerative colitis), improved control of disease activity has led to a trend of decreasing colectomy rates for refractory disease. Consequently, indications for colectomy for dysplasia and colorectal cancer seem to be increasing. Advances have not only been made in surgical techniques, but also in multidisciplinary approaches, the timing of surgery, and in medical management before and after surgery. This Review discusses surgical indications in patients with ulcerative colitis in relation to current medical therapy, management in the acute setting, indications for staged procedures, new techniques such as transanal surgery and robotics, and surgical alternatives to ileal pouch-anal anastomosis. A multidisciplinary approach including surgeons, gastroenterologists, pathologists, radiologists, and clinical nutritionists is essential to improving patient outcomes in different clinical scenarios of ulcerative colitis management in the 21st century.

Safety and efficacy of tofacitinib for treatment of ulcerative colitis: final analysis of OCTAVE Open, an open-label, long-term extension study with up to 7.0 years of treatment.

BACKGROUND: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We present final data from OCTAVE Open, an open-label, long-term extension study. AIMS: The primary objective of OCTAVE Open was to assess the safety and tolerability of long-term tofacitinib in patients with ulcerative colitis; evaluating efficacy was a secondary objective. METHODS: Eligible patients included OCTAVE Induction 1&2 non-responders and OCTAVE Sustain completers/treatment failures. Patients in remission at OCTAVE Open baseline received tofacitinib 5 mg b.d.; all others received 10 mg b.d. Incidence rates (unique patients with events/100 patient-years) for adverse events of special interest were calculated; ≤7.0 years of observation. Efficacy endpoints derived from Mayo score were reported ≤36 months (last scheduled endoscopy visit). RESULTS: In OCTAVE Open, 769 of 944 patients (81.5%) initially received tofacitinib 10 mg b.d. Among all patients (2440.8 patient-years of exposure), incidence rates (IRs; 95% confidence intervals) for deaths and adverse events of special interest were: deaths, 0.25 (0.09-0.54); serious infections, 1.61 (1.14-2.20); herpes zoster (non-serious and serious), 3.16 (2.47-3.97); opportunistic infections, 0.87 (0.54-1.33); major adverse cardiovascular events, 0.16 (0.04-0.42); malignancies (excluding non-melanoma skin cancer), 1.03 (0.67-1.52); non-melanoma skin cancer, 0.75 (0.45-1.19); deep vein thrombosis, 0.04 (0.00-0.23); pulmonary embolism, 0.21 (0.07-0.48). At Month 36, 66.9% and 40.3% showed clinical response, 64.6% and 37.1% had endoscopic improvement, and 58.9% and 33.7% maintained or achieved remission, with tofacitinib 5 and 10 mg b.d. respectively. CONCLUSION: Tofacitinib demonstrated consistent safety up to 7.0  years. Data collected up to Month 36 support long-term efficacy beyond the 52-week maintenance study.

Temporal trends in the epidemiology of inflammatory bowel diseases in the public healthcare system in Brazil: A large population-based study.

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.

HEALTH-RELATED QUALITY OF LIFE IN ADOLESCENTS AND YOUNG ADULTS WITH INFLAMMATORY BOWEL DISEASE IS ASSOCIATED WITH REDUCTION IN SCHOOL AND WORK PRODUCTIVITY RATHER THAN PHYSICAL IMPAIRMENT: A MULTIDISCIPLINARY STUDY.

BACKGROUND: Inflammatory bowel diseases (IBD), comprising Crohn's disease and ulcerative colitis, are chronic inflammatory diseases of the gastrointestinal tract that often have their onset among adolescents and young adults (AYA). IBD are characterized by episodes of active disease interspersed with periods of remission, and its activity is inversely correlated with health-related quality of life (HRQL). OBJECTIVE: This study aimed to determine whether AYA in remission or with low IBD activity would exhibit HRQL similar to that of age-matched healthy individuals, and whether demographic and disease factors could affect HRQL using a 'patient-reported outcome' instrument. METHODS: This study enrolled only AYA with IBD, with low activity. This research included five multidisciplinary clinics of two academic hospitals: Paediatric Gastroenterology, Gastroenterology, Coloproctology, Paediatric Rheumatology and Adolescent divisions, São Paulo, Brazil. A total of 59 AYA with IBD (age, 13-25 years) and 60 healthy AYA (age, 13-25 years) completed the Pediatric Quality of Life Inventory 4.0 and 36-Item Short-Form Health Survey questionnaires and the visual analogue scale (VAS) for pain. Demographic data, extra-intestinal manifestations, treatment, and outcomes regarding CD and UC were evaluated. RESULTS: AYA with IBD and healthy controls were similar with respect to median ages (18.63 [13.14-25.80] years vs 20.5 [13.68-25.84] years, P=0.598), proportion of female sex (42% vs 38%, P=0.654), and percentage of upper middle/middle Brazilian socioeconomic classes (94% vs 97%, P=0.596). The school/work score was significantly lower in AYA with IBD than in healthy controls (70 [10-100] vs 75 [5-100], P=0.037). The 'general health-perception' score was significantly lower in AYA with IBD than in healthy controls (50 [10-80] vs 0 [25-90], P=0.0002). The median VAS, FACES pain rating scale, and total VAS scores were similar between the two groups (2 [0-10] vs 3 [0-9], P=0.214). No association between HRQL and clinical and demographic parameters was identified among IBD patients. CONCLUSION: AYA with low IBD activity reported poor HRQL in school/work and general health perception domains, which highlights a disability criterion in this vulnerable population.

A qualidade de vida relacionada à saúde em adolescentes e adultos jovens com doença inflamatória intestinal está mais associada à redução na produtividade escolar e no trabalho do que ao comprometimento físico: um estudo multidisciplinar / Health-related quality of life in adolescents and young adults with inflammatory bowel disease is associated with reduction in school and work productivity rather than physical impairment: a multidisciplinary study

ABSTRACT BACKGROUND: Inflammatory bowel diseases (IBD), comprising Crohn's disease and ulcerative colitis, are chronic inflammatory diseases of the gastrointestinal tract that often have their onset among adolescents and young adults (AYA). IBD are characterized by episodes of active disease interspersed with periods of remission, and its activity is inversely correlated with health-related quality of life (HRQL). OBJECTIVE: This study aimed to determine whether AYA in remission or with low IBD activity would exhibit HRQL similar to that of age-matched healthy individuals, and whether demographic and disease factors could affect HRQL using a 'patient-reported outcome' instrument. METHODS: This study enrolled only AYA with IBD, with low activity. This research included five multidisciplinary clinics of two academic hospitals: Paediatric Gastroenterology, Gastroenterology, Coloproctology, Paediatric Rheumatology and Adolescent divisions, São Paulo, Brazil. A total of 59 AYA with IBD (age, 13-25 years) and 60 healthy AYA (age, 13-25 years) completed the Pediatric Quality of Life Inventory 4.0 and 36-Item Short-Form Health Survey questionnaires and the visual analogue scale (VAS) for pain. Demographic data, extra-intestinal manifestations, treatment, and outcomes regarding CD and UC were evaluated. RESULTS: AYA with IBD and healthy controls were similar with respect to median ages (18.63 [13.14-25.80] years vs 20.5 [13.68-25.84] years, P=0.598), proportion of female sex (42% vs 38%, P=0.654), and percentage of upper middle/middle Brazilian socioeconomic classes (94% vs 97%, P=0.596). The school/work score was significantly lower in AYA with IBD than in healthy controls (70 [10-100] vs 75 [5-100], P=0.037). The 'general health-perception' score was significantly lower in AYA with IBD than in healthy controls (50 [10-80] vs 0 [25-90], P=0.0002). The median VAS, FACES pain rating scale, and total VAS scores were similar between the two groups (2 [0-10] vs 3 [0-9], P=0.214). No association between HRQL and clinical and demographic parameters was identified among IBD patients. CONCLUSION: AYA with low IBD activity reported poor HRQL in school/work and general health perception domains, which highlights a disability criterion in this vulnerable population.

RESUMO CONTEXTO: As doenças inflamatórias intestinais (DII), que englobam a doença de Crohn e a colite ulcerativa, são doenças inflamatórias crônicas do trato gastrointestinal que frequentemente se manifestam em adolescentes e adultos jovens (AAJ). As DII são caracterizadas por episódios de doença ativa intercalados com períodos de remissão, e sua atividade se correlaciona inversamente com a qualidade de vida relacionada à saúde (QVRS). OBJETIVO: Este estudo teve como objetivo determinar se AAJ em remissão ou com baixa atividade de DII exibiria QVRS semelhante à de indivíduos saudáveis pareados por idade, e se fatores demográficos da doença poderiam afetar a QVRS usando um instrumento de medidas de desfecho relatadas pelo paciente. MÉTODOS: Este estudo envolveu apenas AAJ com DII, com baixa atividade. Esta pesquisa incluiu cinco clínicas multidisciplinares de dois Hospitais Universitários: Divisões de Gastroenterologia Pediátrica, Gastroenterologia, Coloproctologia, Reumatologia Pediátrica e Adolescentes, São Paulo, Brasil. Um total de 59 AAJ com DII (13-25 anos de idade) e 60 AAJ controle saudáveis (13-25 anos de idade) responderam os questionários Pediatric Quality of Life Inventory 4.0 e 36-Item Short-Form Health Survey e as escalas visuais de dor. Dados demográficos, manifestações extra intestinais, tratamentos e desfechos da doença de Crohn e a colite ulcerativa foram avaliados. RESULTADOS: AAJ com DII e os controles saudáveis foram grupos semelhantes com relação à média de idade (18,63 [13,14-25,80] vs 20,5 [13,68-25,84] anos, P=0,598), quanto à proporção de pacientes do sexo feminino (42% vs 38%, P=0,654), e quanto à porcentagem da classe socioeconômica brasileira média elevada/ média (94% vs 97%, P=0,596). Os escores escola/trabalho foram significativamente mais baixos nos AAJ com DII do que nos controles saudáveis (70 [10-100] vs 75 [5-100], P=0,037). O escore 'percepção geral de saúde' foi significativamente mais baixo nos AAJ com DII do que no agrupamento controle saudável (50 [10-80] vs 0 [25-90], P=0,0002). As escalas de avaliação visual de dor foram semelhantes entre os dois grupos (2 [0-10] vs 3 [0-9], P=0,214). Nenhuma associação entre QVRS e parâmetros clínicos e demográficos foi identificada entre os pacientes com DII. CONCLUSÃO: AAJ com baixa atividade das DII relataram baixa QVRS nos domínios da escola/trabalho e percepção geral da saúde, o que destaca um critério de incapacidade nesta vulnerável população.

Risk of thrombosis and mortality in inflammatory bowel disease.

OBJECTIVES: Patients with inflammatory bowel disease have a higher risk of thrombosis, which is associated with a higher morbidity and mortality. Most data about VTE are related to hospitalized patients with active disease, but several cases happen in the outpatient setting, and are not covered by current prophylaxis recommendation. As the knowledge of VTE in outpatients is still poor, the aim of this study is to evaluate the risk, clinical data and mortality of thrombosis in patients followed in our center, comparing our findings with the current prophylaxis recommendation. METHODS: The medical electronic chart of 1093 inflammatory bowel disease patients and their image exams were actively searched for words related to thrombosis, followed by charts reviewed to collect information about the event and data regarding clinical settings and thrombosis profile. RESULTS: Overall, 654 Crohn's and 439 Colitis patients were included. Thrombosis prevalence was 5.1%,and mortality rate was higher in patients who had suffered thrombosis (10.71% vs. 1.45%, OR 8.0). Half of them developed thrombosis in the outpatient setting, 52% of these had disease activity, 17% had recent hospitalization, and 10% had previous thrombosis. In 27% of cases, diagnosis was done by routine image exams, with no clinical symptoms or previous history of thrombosis. None of them had used thromboprophylaxis. However, a great majority of patients who had thrombosis during hospitalization used heparin prophylaxis. CONCLUSION: Inflammatory bowel disease patients who develop thrombosis have an increased mortality risk. A significant proportion of the events happened in patients without a clear thromboprophylaxis recommendation or in those receiving heparin prophylaxis.

Postoperative Approach for Crohn's Disease: The Right Therapy to the Right Patient.

BACKGROUND: Recurrence is a common event after surgical resections secondary to Crohn's disease (CD). Endoscopic signs of inflammation, defined as postoperative endoscopic recurrence (PER) occur in up to 90% of the patients after one year. PER precedes clinical recurrence and further need for reoperations due to consequent bowel damage. Therefore, controlling inflammation after surgery in a preventive way is essential for disease control. OBJECTIVE: to review data regarding PER in CD, and demonstrate algorithms for its management after surgery. RESULTS: There is no fixed strategy to prevent recurrence after surgery in CD. There are several risk factors that must be taken into consideration to guide physicians to choose the best therapeutic agents and strategies in this scenario. In this review, the authors describe in details the stratification based on risk factors, the therapeutic agents mostly used to prevent recurrence and discuss the several options for the postoperative management in CD. CONCLUSIONS: No fixed strategy is recommended after surgical resections in CD. Thus, the need for a personalized approach for each patient is emphasized, in accordance with several conditions and variables.

Prevalence of celiac disease among blood donors in São Paulo: the most populated city in Brazil.

OBJECTIVE: Celiac disease is a permanent enteropathy caused by the ingestion of gluten, which leads to an immunemediated inflammation of the small intestine mucosa. The prevalence of celiac disease varies among different nations and ethnic backgrounds, and its diversity is determined by genetic and environmental factors. São Paulo city is one of the largest cities in the world, with a vast population and an important history of internal migratory flow from other Brazilian regions, as well as immigration from other, primarily European, countries, resulting in significant miscegenation. The aim of the present study was to estimate the prevalence of adults with undiagnosed celiac disease among blood donors of São Paulo by collecting information on the ancestry of the population studied. METHODS: The prevalence of celiac disease was assessed by screening for positive IgA transglutaminase and IgA endomysium antibodies in 4,000 donors (volunteers) in the Fundação Pró-Sangue Blood Center of São Paulo, São Paulo, Brazil. The antibody-positive subjects were asked to undergo a small bowel biopsy. RESULTS: Of the 4,000 subjects, twenty-four had positive tests, although both antibody tests were not always concordant. For example, ten subjects were positive for IgA tissue transglutaminase only. In twenty-one positive patients, duodenal biopsies were performed, and the diagnosis of celiac disease was confirmed in fourteen patients (Marsh criteria modified by Oberhuber). In this group, 67% claimed to have European ancestry, mainly from Italy, Portugal and Spain. CONCLUSION: The prevalence of celiac disease is at least 1:286 among supposedly healthy blood bank volunteers in São Paulo, Brazil.

Prevalence of celiac disease among blood donors in São Paulo: the most populated city in Brazil

OBJECTIVE: Celiac disease is a permanent enteropathy caused by the ingestion of gluten, which leads to an immunemediated inflammation of the small intestine mucosa. The prevalence of celiac disease varies among different nations and ethnic backgrounds, and its diversity is determined by genetic and environmental factors. São Paulo city is one of the largest cities in the world, with a vast population and an important history of internal migratory flow from other Brazilian regions, as well as immigration from other, primarily European, countries, resulting in significant miscegenation. The aim of the present study was to estimate the prevalence of adults with undiagnosed celiac disease among blood donors of São Paulo by collecting information on the ancestry of the population studied. METHODS: The prevalence of celiac disease was assessed by screening for positive IgA transglutaminase and IgA endomysium antibodies in 4,000 donors (volunteers) in the Fundação Pró-Sangue Blood Center of São Paulo, São Paulo, Brazil. The antibody-positive subjects were asked to undergo a small bowel biopsy. RESULTS: Of the 4,000 subjects, twenty-four had positive tests, although both antibody tests were not always concordant. For example, ten subjects were positive for IgA tissue transglutaminase only. In twenty-one positive patients, duodenal biopsies were performed, and the diagnosis of celiac disease was confirmed in fourteen patients (Marsh criteria modified by Oberhuber). In this group, 67% claimed to have European ancestry, mainly from Italy, Portugal and Spain. CONCLUSION: The prevalence of celiac disease is at least 1:286 among supposedly healthy blood bank volunteers in São Paulo, Brazil.

Prevalence of celiac disease in an urban area of Brazil with predominantly European ancestry.

AIM: To determine the prevalence of celiac disease in a group of volunteer blood donors at a blood bank in the city of Curitiba, Brazil through detection of the serum marker immunoglobulin A (IgA) antitransglutaminase antibody. METHODS: Blood samples collected from 2086 healthy subjects at the Paraná State Center for Hematology and Hemotherapy in Curitiba were submitted to ELISA testing for the IgA antitransglutaminase antibody. Positive samples received IgA antiendomysium antibody test through indirect immunofluorescence using human umbilical cord as substrate. Subsequently, patients who were positive on both tests underwent small bowel (distal duodenum) biopsy. RESULTS: Six subjects, four males and two females, tested positive for the two serum markers. Five of the six were submitted to intestinal biopsy (one declined the procedure). Biopsy results revealed changes in the distal duodenum mucosa (three classified as Marsh IIIb lesions and two as Marsh II lesions). Most donors diagnosed having celiac disease presented multiple symptoms (gastrointestinal tract complaints). One donor reported having a family history of celiac disease (in a niece). CONCLUSION: Among apparently healthy blood donors, the prevalence of biopsy-confirmed celiac disease was approximately 1:417, similar to that seen in European countries.

Ursodeoxycholic acid ameliorates experimental ileitis counteracting intestinal barrier dysfunction and oxidative stress.

The aim of this study was to evaluate the effect of ursodeoxycholic acid (UDCA) on intestinal permeability (IP) and reactive oxygen species (ROS) generation in indomethacin-induced enteropathy, a well-known experimental model of Crohn's disease. Seventy-eight male Wistar rats were randomly assigned to receive indomethacin, indomethacin + UDCA, or vehicles. Indomethacin induced a significant increase in the fraction of urinary excretion of 51Cr-EDTA following oral administration (7.9 +/- 1.3 vs 2.3 +/- 0.2%; P < 0.05) and lucigenin-amplified chemiluminescence in intestinal fragments ex vivo (10.1 +/- 1.9 vs 2.6 +/- 0.4 cpm x 10(3)/mg; P < 0.05) compared to controls. UDCA significantly reversed these effects (P < 0.05), without being incorporated in biliary bile acid composition (HPLC analysis). These findings support a local protective effect of UDCA in experimental ileitis by the modulation of intestinal barrier dysfunction and oxidative stress. In short, they provide insights into mechanisms of action of UDCA in intestinal inflammation and a new perspective on the treatment of Crohn's disease.

Celiac disease in Brazilian adults.

UNLABELLED: Forty-eight adult patients with celiac disease between 15 and 68 years of age (mean, 41 years) were studied. Sixty-seven percent were female and 33% were male patients. Most of the patients were white (98%). The main clinical features were diarrhea (90%), weight loss (70%), and abdominal pain (56%). On physical examination, the main findings were pallor (40%), aphthous stomatitis (31%), and arthralgia (23%). Associated disorders included diabetes mellitus type I, osteoporosis, and atopy (6% each); dermatitis herpetiformis and depression (4% each); and hypothyroidism, hyperthyroidism, duodenal carcinoma, and Gilbert syndrome (2% each). The histologic results according to Marsh criteria (modified by Rostami) are as follows: type I, 10%; type II, 21%; type IIIa, 19%; type IIIb, 17%; and type IIIc, 33%. The sensitivity and specificity for the antiendomysium antibody-immunoglobulin A test were 92% and 100%, respectively, when considering the whole group of patients; however, the sensitivity (but not the specificity) decreased to 86% when taking into account only the group of patients with mild histologic alterations (Marsh type I, II, and IIIa). CONCLUSION: In general, the authors' results are similar to those described in developing countries, indicating that celiac disease might have the same spectrum of presentation regardless of the region studied.

Doença celíaca no adulto / Coeliac disease in adults

The coeliac disease is characterized by lesions of variable degrees in the mucosa of proximal smalll bowel. This lesions are caused by gluten ingestion in people thar have genetic prodisponition for this disease with emphasis on diagnosis, the assocation with another disordes and treatment, wich is based in a gluten-free diet (au)