Evaluation of oxidative stress in an experimental model of Crohn's disease treated with hyperbaric oxygen therapy.

INTRODUCTION: Treatments of Inflammatory Bowel Disease (IBD) are able to control symptoms in most cases, however, a fraction of patients do not improve or have a loss of response to treatments, making it important to explore new therapeutic strategies. Hyperbaric oxygen therapy (HBO) may represent one of them. The aim of this study was to evaluate the effects of HBO therapy in an experimental model of IBD. METHODS: Sixty male BALBc mice were divided into six groups. Group 1 was colitis-induced with trinitrobenzene sulfonic acid (TNBS) + ethanol, group 2 received TNBS + ethanol plus HBO, group 3 received only ethanol, group 4 received ethanol plus HBO, group 5 received saline solution, and group 6 received saline solution plus HBO. HBO was performed for four days, subsequently, the mice were evaluated daily. At the end of the study, samples from the intestine were collected for histological analysis as well as for measurement of antioxidant enzymes and cytokine levels. RESULTS: HBO significantly improved the clinical and histological status of the animals. Treatment with HBO increased the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) in all of the groups; moreover, the difference was only significant between the TNBS and TNBS + HBO groups and treatments promoted a reduction in the proinflammatory cytokines IFN-γ, IL-12, IL-17 and TNF-α and increased the anti-inflammatory cytokines IL-4 and IL-10, with no changes in IL-13. CONCLUSION: HBO effectively treats TNBS-induced colitis by increasing the activity of antioxidant enzymes and modulating cytokine profiles.

Efficacy of Early Optimization of Infliximab Guided by Therapeutic Drug Monitoring during Induction-A Prospective Trial.

Therapeutic drug monitoring (TDM) during induction therapy with anti-tumor necrosis factor drugs has emerged as a strategy to optimize response to these biologics and avoid undesired outcomes related to inadequate drug exposure. This study aimed to describe clinical, biological, and endoscopic remission rates at six months in Brazilian inflammatory bowel disease (IBD) patients following a proactive TDM algorithm guided by IFX trough levels (ITL) and antibodies to IFX (ATI) levels during induction, at week six. A total of 111 IBD patients were prospectively enrolled, excluding those previously exposed to the drug. ITL ≥ 10 µg/mL was considered optimal. Patients with suboptimal ITL (<10 µg/mL) were guided according to ATI levels. Those who presented ATI ≤ 200 ng/mL underwent dose intensification in the maintenance phase, and patients with ATI > 200 ng/mL discontinued IFX. In our study, proactive TDM was associated with persistence in the IFX rate at six months of 82.9%. At that time, rates of clinical, biological, and endoscopic remission in patients under IFX treatment were 80.2%, 73.9%, and 48.1%, respectively. Applying a simplified TDM-guided algorithm during induction seems feasible and can help improve patients' outcomes in clinical practice.

Evaluation of oxidative stress in an experimental model of Crohn's disease treated with hyperbaric oxygen therapy

Abstract Introduction: Treatments of Inflammatory Bowel Disease (IBD) are able to control symptoms in most cases, however, a fraction of patients do not improve or have a loss of response to treatments, making it important to explore new therapeutic strategies. Hyperbaric oxygen therapy (HBO) may represent one of them. The aim of this study was to evaluate the effects of HBO therapy in an experimental model of IBD. Methods: Sixty male BALBc mice were divided into six groups. Group 1 was colitis-induced with trinitrobenzene sulfonic acid (TNBS) + ethanol, group 2 received TNBS + ethanol plus HBO, group 3 received only ethanol, group 4 received ethanol plus HBO, group 5 received saline solution, and group 6 received saline solution plus HBO. HBO was performed for four days, subsequently, the mice were evaluated daily. At the end of the study, samples from the intestine were collected for histological analysis as well as for measurement of antioxidant enzymes and cytokine levels. Results: HBO significantly improved the clinical and histological status of the animals. Treatment with HBO increased the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) in all of the groups; moreover, the difference was only significant between the TNBS and TNBS + HBO groups and treatments promoted a reduction in the proinflammatory cytokines IFN-γ, IL-12, IL-17 and TNF-α and increased the anti-inflammatory cytokines IL-4 and IL-10, with no changes in IL-13. Conclusion: HBO effectively treats TNBS-induced colitis by increasing the activity of antioxidant enzymes and modulating cytokine profiles.

Metaboloma use in ophthalmology / Uso de metaboloma em oftalmologia: uma revisão narrativa

ABSTRACT It is part of the omic sciences to search for an understanding of how the cellular system of organisms works as well as studying their biological changes. As part of the omic sciences, we can highlight the genomics whose function is the study of genes, the transcriptomics that studies the changes in the transcripts, the proteomics responsible for understanding the changes that occur in proteins, and the metabolomics that studies all the metabolic changes that occur in a certain system when it is submitted to different types of stimuli. Metabolomics is the science that studies the endogenous and exogenous metabolites in biological systems, which aims to provide comparative quantitative or semi-quantitative information about all metabolites in the system. This review aims to describe the main applications of metabolomics science in ophthalmolog. We searched the literature on main applications of metabolomics science in ophthalmology, using the MEDLINE and LILACS databases, with the keywords "metabolomics" and "ophthalmology", from January 1, 2009, to April 5, 2021. We retrieved 216 references, of which 58 were considered eligible for intensive review and critical analysis. The study of the metabolome allows a better understanding of the metabolism of ocular tissues. The results are important to aid diagnosis and as predictors of the progression of many eye and systemic diseases.

RESUMO Faz parte das ciências ômicas buscar entender como funciona o sistema celular dos organismos e estudar suas alterações biológicas. Como parte das ciências ômicas, destacam-se a genômica, cuja função é o estudo dos genes; a transcriptômica, que estuda as mudanças nos transcritos; a proteômica, responsável por entender as mudanças que ocorrem nas proteínas, e a metabolômica, que estuda todo o metabolismo das alterações que ocorrem em um determinado sistema quando ele é submetido a diferentes tipos de estímulos. A metabolômica é a ciência que estuda os metabólitos endógenos e exógenos em sistemas biológicos, visando fornecer informações comparativas quantitativas ou semiquantitativas sobre todos os metabólitos do sistema. Esta revisão teve como objetivo descrever as principais aplicações da ciência metabolômica na oftalmologia. Trata-se de revisão narrativa desenvolvida por um grupo de pesquisa da Universidade Federal de São Paulo, em São Paulo (SP). Buscaram-se, na literatura, as principais aplicações da ciência metabolômica em oftalmologia, utilizando as bases de dados Medline® e Lilacs, com as palavras-chave "metabolomics" e "oftalmologia", de 1º de janeiro de 2009 a 5 de abril de 2021. Foram recuperadas 216 referências, das quais 58 foram consideradas elegíveis para revisão intensiva e análise crítica. O estudo do metaboloma permite um melhor entendimento do metabolismo dos tecidos oculares. Os resultados são importantes para auxiliar no diagnóstico e como preditores da progressão de muitas doenças oculares e sistêmicas.

Nutritional Global Status and Its Impact in Crohn's Disease.

BACKGROUND: Malnutrition among inflammatory bowel disease (IBD) subjects is well documented in literature and may emerge from factors including inadequate dietary intake, malabsorption and disease activity. The aim of this study was to complete a comprehensive nutrition assessment and explore what possibilities may help bring a better quality of life for IBD subjects. METHODS: Nutritional status based on biochemical tests, body composition and body mass index (BMI). Food intake was assessed by an alternate 3-day food record and the adequacy of intake was evaluated according to national and international references. Clinical disease activity was evaluated by the Harvey-Bradshaw index and CRP levels. RESULTS: The study included 217 patients and 65 controls, where 54.4% of these patients were classified as normal weight with a mean BMI lower than controls (23.8 ± 4.9 versus 26.9 ± 4.8 kg/m2, P = 0.02). Patients with disease activity showed more overweight and obesity than patients with controlled disease. Vitamin B12 deficiency was present in 19% of Crohn's disease (CD), mainly in patients with ileal commitment and small bowel resections. Anemia was present in 21.7% of patients, being more common in patients with active disease (25%) and bowel resection (23%). Regarding calorie intake (EI), CD group ingested more than controls (1986.3 ± 595.9 kcal versus 1701.8 ± 478.9 kcal; P = 0.003). CONCLUSIONS: CD patients presented micronutrient deficiency when compared with controls, explained for other reasons than intake restrictions. Also, fat excess might have contributed to disease burden as continuously reported in the literature.

Recovery from COVID-19 Pneumonia in a Patient with Acute Severe Colitis.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has increased concern regarding SARS-CoV-2 infection in inflammatory bowel disease (IBD) patients, especially those on immunosuppressive therapies or with active disease. There are limited reports describing the clinical features of COVID-19 in an IBD population, and the impact of immunosuppression on the severity of the infection remains unclear. CASE REPORT: A 33-year-old female patient with a long history of ulcerative colitis, poorly controlled, was admitted with COVID-19 a few days after being discharged from the hospital for treatment of acute severe ulcerative colitis. High-risk factors for COVID-19 complications, i.e., high-dose steroids (40 mg prednisone) and severe active disease, were present at admission. Despite the development of extensive pulmonary involvement, the patient had a favorable outcome. DISCUSSION: Management of IBD patients during the COVID-19 pandemic has been challenging. Measures to minimize the potential risk of SARS-CoV-2 infection, including strict social distancing and self-isolation, in the IBD population have been recommended, especially for high-risk patients. Although steroid tapering and persistence of biologics are advised by professional groups, the best treatment strategy for IBD patients presenting a flare during the outbreak has yet to be defined.

Management of inflammatory bowel disease patients in the COVID-19 pandemic era: a Brazilian tertiary referral center guidance.

The world is fighting the COVID-19 outbreak and health workers, including inflammatory bowel diseases specialists, have been challenged to address the specific clinical issues of their patients. We hereby summarize the current literature in the management of inflammatory bowel disease (IBD) patients during the COVID-19 pandemic era that support the rearrangement of our IBD unit and the clinical advice provided to our patients.

Management of inflammatory bowel disease patients in the COVID-19 pandemic era: a Brazilian tertiary referral center guidance

The world is fighting the COVID-19 outbreak and health workers, including inflammatory bowel diseases specialists, have been challenged to address the specific clinical issues of their patients. We hereby summarize the current literature in the management of inflammatory bowel disease (IBD) patients during the COVID-19 pandemic era that support the rearrangement of our IBD unit and the clinical advice provided to our patients

Endoscopic activity, tissue factor and Crohn's disease: findings in clinical remission patients.

BACKGROUND: As Crohn's disease (CD) is associated with a high risk of thromboembolic events (TE), including patients with subclinical inflammation, we aim to evaluate the correlation between the impact of endoscopic activity (EA) in the coagulation profiling of CD patients while in clinical remission. METHODS: From 164 consecutive CD patients included in clinical remission [Crohn's disease activity index (CDAI) < 150], 75 were in the EA group [Simplified Endoscopic Score for CD (SES-CD) ⩾ 7], 89 were in the endoscopic remission (ER) group (SES-CD ⩽ 2), and 50 were included as healthy controls in the study. Blood samples were analyzed for tissue factor (TF), factor VIII (FVIII), thrombomodulin (TM), ADAMTS-13, von Willebrand factor (VWF), and endogenous thrombin potential (ETP), as well as collecting data regarding risk factors for TE and CD profile. RESULTS: Mean plasma TF activity showed significantly higher levels in the EA group when compared with the ER and control groups (127 pM versus 103 pM versus 84 pM; p = 0.001), although the VWF:Ag (160% versus 168% versus 110%; p = 0.001), VWF/ADAMTS-13 (191 versus 219 versus 138; p = 0.003), FVIII (150% versus 144% versus 90%; p = 0.001) and TM (5.13 ng/ml versus 4.91 ng/mL versus 3.81 ng/ml; p < 0.001) were only increased in CD regardless of EA status when compared with controls. Lastly, ETP with and without TM remained the same in all three groups. CONCLUSIONS: CD patients in clinical remission with EA present endothelial lesion inducing TF exposure and subsequent coagulation cascade activation. Recommended thromboprophylaxis for EA outpatient subgroups will require additional investigation in order to be validated.

Management of inflammatory bowel disease patients in the COVID-19 pandemic era: a Brazilian tertiary referral center guidance

The world is fighting the COVID-19 outbreak and health workers, including inflammatory bowel diseases specialists, have been challenged to address the specific clinical issues of their patients. We hereby summarize the current literature in the management of inflammatory bowel disease (IBD) patients during the COVID-19 pandemic era that support the rearrangement of our IBD unit and the clinical advice provided to our patients.

Pancreatic endosonographic findings and clinical correlation in Crohn's disease.

OBJECTIVES: We aimed to evaluate the incidence of pancreatic alterations in Crohn's disease using endoscopic ultrasound (EUS) and to correlate the number of alterations with current clinical data. METHODS: Patients diagnosed with Crohn's disease (n=51) were examined using EUS, and 11 variables were analyzed. A control group consisted of patients with no history of pancreatic disease or Crohn's disease. Patients presenting with three or more alterations underwent magnetic resonance imaging (MRI). Pancreatic function was determined using a fecal elastase assay. RESULTS: Two of the 51 patients (3.9%) presented with four EUS alterations, 3 (5.9%) presented with three, 11 (21.5%) presented with two, and 13 (25.5%) presented with one; in the control group, only 16% presented with one EUS alteration (p<0.001). Parenchymal abnormalities accounted for 39 of the EUS findings, and ductal abnormalities accounted for 11. Pancreatic lesions were not detected by MRI. Low fecal elastase levels were observed in 4 patients, none of whom presented with significant pancreatic alterations after undergoing EUS. Ileal involvement was predictive of the number of EUS alterations. CONCLUSION: A higher incidence of pancreatic abnormalities was found in patients with Crohn's disease than in individuals in the control group. The majority of these abnormalities are related to parenchymal alterations. In this group of patients, future studies should be conducted to determine whether such morphological abnormalities could evolve to induce exocrine or endocrine pancreatic insufficiency and, if so, identify the risk factors and determine which patients should undergo EUS.

Pancreatic endosonographic findings and clinical correlation in Crohn's disease

OBJECTIVES: We aimed to evaluate the incidence of pancreatic alterations in Crohn's disease using endoscopic ultrasound (EUS) and to correlate the number of alterations with current clinical data. METHODS: Patients diagnosed with Crohn's disease (n=51) were examined using EUS, and 11 variables were analyzed. A control group consisted of patients with no history of pancreatic disease or Crohn's disease. Patients presenting with three or more alterations underwent magnetic resonance imaging (MRI). Pancreatic function was determined using a fecal elastase assay. RESULTS: Two of the 51 patients (3.9%) presented with four EUS alterations, 3 (5.9%) presented with three, 11 (21.5%) presented with two, and 13 (25.5%) presented with one; in the control group, only 16% presented with one EUS alteration (p<0.001). Parenchymal abnormalities accounted for 39 of the EUS findings, and ductal abnormalities accounted for 11. Pancreatic lesions were not detected by MRI. Low fecal elastase levels were observed in 4 patients, none of whom presented with significant pancreatic alterations after undergoing EUS. Ileal involvement was predictive of the number of EUS alterations. CONCLUSION: A higher incidence of pancreatic abnormalities was found in patients with Crohn's disease than in individuals in the control group. The majority of these abnormalities are related to parenchymal alterations. In this group of patients, future studies should be conducted to determine whether such morphological abnormalities could evolve to induce exocrine or endocrine pancreatic insufficiency and, if so, identify the risk factors and determine which patients should undergo EUS.

Helminths as an alternative therapy for intestinal diseases.

Animal models and clinical studies have shown that helminth infections exert immunomodulatory activity, altering intestinal permeability and providing a potential beneficial action on autoimmune and inflammatory disorders in human beings, such as inflammatory bowel disease (IBD) and celiac disease. This is consistent with the theory that intestinal microbiota is responsible for shaping human immunological responses. With the arrival of the immunobiologic era and the use of antibodies, we propose a distinctive pathway for treating patients with IBD and celiac disease. We have some evidence about the safety and tolerability of helminth use, but evidence about their impact on disease activity is lacking. Using worms to treat diseases could be a possible way to lower treatment costs, since the era of immunobiologic agents is responsible for a significant rise in expenses. Some questions remain to be investigated regarding the use of helminths in intestinal disease, such as the importance of the specific species of helminths used, appropriate dosing regimens, optimal timing of treatment, the role of host genetics, diet, environment, and the elucidation of the exact mechanisms of action. One promising approach is the use of helminth-derived anti-inflammatory molecules as drugs. Yet there are still many challenges with this method, especially with regard to safety. Studies on intestinal permeability point to Strongyloides stercoralis as a useful nematode for these purposes.

Inter- and intraobserver agreement in computed tomography enterography in inflammatory bowel disease.

AIM: To evaluate intra- and interobserver agreement in imaging features in inflammatory bowel disease and comparison with fecal calprotectin (FC) levels. METHODS: Our institutional computed tomography enterography (CTE) database was retrospectively queried to identify patients who underwent CTE from January 2014 to June 2015. Patient inclusion criteria were confirmed inflammatory bowel disease (IBD) and FC collected < 4 mo after CTE without any change in clinical treatment or surgical treatment during this interval. The exclusion criterion was poor image quality. Two blinded abdominal radiologists, with 12 and 3 years of experience analyzed the CTE regarding localization (small bowel, colonic, both, or no disease detected); type of IBD (inflammatory, stenosing, fistulizing, > 1 pattern, or normal); and signs of active disease (present or absent). In 42 of 44 patients evaluated, routine CTE reports were made by one of the readers who re-evaluated the CTEs ≥ 6 mo later, to determine the intraobserver agreement. FC was considered a sign of disease activity when it was higher than 250 µg/g. RESULTS: Forty-four patients with IBD (38 with Crohn's disease and 6 with ulcerative colitis) were included. There was a moderate interobserver agreement regarding localization of IBD (κ = 0.540), type of disease (κ = 0.410) and the presence of active signs in CTE (κ = 0.419). There was almost perfect intraobserver agreement regarding localization, type and signs of active disease in IBD. The κ values were 0.902, 0.937 and 0.830, respectively. After a consensus between both radiologists regarding inflammatory activity in CTE, we found that 24 (85.7%) of 28 patients who were classified with active disease had elevated FC, and six (37.5%) of 16 patients without inflammatory activity in CTE had elevated FC (P = 0.003). The correlation between elevated FC and the presence of active disease in CTE was significant (κ = 0.495, P = 0.001). CONCLUSION: We found almost perfect intraobserver and moderate interobserver agreement in the signs of active disease in CTE with concurrence of high FC levels.

Tripla infecção com HTLV-1, leishmaniose visceral e estrongiloidíase complicada por pancreatite aguda / Triple infection with HTLV-1, visceral leishmaniasis and strongyloidiasis complicated by acute pancreatitis

lntrodução: a estrongiloidíase tem grande importância médica devido à capacidade de o Strongyloides stercoralis completar seu ciclo de vida no homem e gerar a síndrome de hiperinfecção principalmente em imunocomprometidos. Devido à dificuldade em estruturar a resposta Th2, os pacientes infectados com o Vírus Linfotrópico de Células T Humanas Tipo 1 (HTLV-1) têm maior tendência a apresentar infecção maciça. A leishmaniose visceral, doença relevante em países em desenvolvimento, causa alterações imunológicas semelhantes, porém há poucos relatos de suscetibilidade específica ao Strongyloides stercoralis nos infectados por Leishmania sp. O presente trabalho tem objetivo de relatar um caso de coinfecção HTLV e calazar, que apresentou-se como pancreatite aguda e enteropatia perdedora de proteínas secundárias à estrongiloidíase maciça. Relato de caso: trata-se de um paciente de 34 anos com história de leishmaniose prévia que deu entrada no nosso Serviço com pancreatite aguda idiopática leve, além de história de diarreia crônica há um ano com anasarca e hipoalbuminemia associadas. Apresentou endoscopia digestiva alta com atrofia duodenal importante, tendo sido identificados Strongyloides stercoralis em biópsia, além de sorologia para HTLV positiva. Apresentou translocação bacteriana com sepse grave de foco abdominal, após início do tratamento com ivermectina, tendo posteriormente evoluído com melhora clínica importante e remissão dos sintomas. Fez investigação com punção de medula óssea, em que foram identificadas as formas amastigotas da leishmania. Discussão e conclusão: a presença de HLTV é um fator de risco para a síndrome de hiperinfecção por Strongyloides stercoralis, tendo predisposto o paciente às manifestações graves e raras descritas. A identificação de leishmania na medula óssea, entretanto, é um fator de risco ainda pouco conhecido para estrongiloidíase disseminada, porém com plausibilidade biológica por afetar o sistema imunológico do hospedeiro.(AU)

Introduction: strongyloidiasis has great medical importance because of the ability of the Strongyloides stercoralis to complete its life cycle in man and cause hyperinfection syndrome especially in immunocompromised hosts. Because of the difficulty in triggering The response, Human T-cell lymphotropic virus type 1 (HTLV-1) infected patients has susceptibility for massive infection. Visceral leishmaniasis, a relevant disease in developing countries, causes similar immunological changes, but there are few reports of specific susceptibility to Strongyloides stercoralis on infected by Leishmania sp. This study aimed to report a case of HTLV and kala azar coinfection, presenting as acute pancreatitis and protein losing enteropathy secondary to massive strongyloidiasis. Case report: a 34-year-old patient previously treated for leishmaniasis has presented at our service with idiopathic acute pancreatitis and chronic diarrhea for one year with anasarca and hypoalbuminemia. Upper endoscopy revealed duodenal atrophy in which biopsy identified Strongyloides stercoralis, and HLTV serology was positive. He presented with bacterial translocation and severe sepsis after first dose of ivermectin, but has clinical improvement and remission of symptoms afterwards. Bone marrow aspiration identified amastigote forms of Leishmania. Discussion and Conclusion: the presence of HLTV is a risk factor for Strongyloides stercoralis hyperinfection, and predisposed this patient to the serious and rare events described. The identification of Leishmania in bone marrow, however, is an poorly known risk factor for disseminated strongyloidiasis, but with biological plausibility because it affects the immune system of the host.(AU)

Ophthalmologic manifestations of celiac disease.

Celiac disease is an autoimmune disorder that affects the small intestine of genetically predisposed individuals. Ophthalmic manifestations are within the extra-intestinal manifestations, and can be divided into those of autoimmune disorders or those due to absorptive disabilities. This article reviewed the ophthalmologic manifestation of celiac disease. Ophthalmic symptoms are rare, but should be investigated in patients with celiac disease and taken into consideration as the first systemic manifestation.

A snapshot of the nutritional status of Crohn's disease among adolescents in Brazil: a prospective cross-sectional study.

BACKGROUND: The relationship between nutrition and Crohn's disease (CD) is complex and involves several therapeutic possibilities including: nutrition treatment for malnourished patients, optimization of growth and development, prevention of osteoporosis, first-line therapy for active disease, and maintenance of disease remission. In children and adolescents with CD, malnutrition is a common problem that adversely affects the prognosis. In at-risk adolescent CD patients, it is important to assess body composition, food intake, energy expenditure, nutrient balance and serum levels of nutrients before planning interventions for this population. The aim of this study was to provide a snapshot of the nutritional status of adolescents with CD in Brazil. METHODS: We prospectively selected 22 patients with mildly to moderately active CD, 29 patients with inactive CD and 35 controls (first-degree relatives of and in the same age bracket as the CD patients). The age range of participants was between 13.2 and 19.4 years old. We collected anthropometric data including weight, height, and body mass index (BMI), which were expressed as Z scores: weight-for-age, height-for-age and BMI-for-age, respectively, as well as using bioimpedance to determine body composition and assessing the Tanner stage. We also assessed macronutrients and micronutrients (serum levels and dietary intake of both). We used the chi-square test to determine whether any of the studied variables were associated with inactive or active CD. The level of significance was set at 5 % (p < 0.05). We have written informed parental consent for participation for any minors and written informed consent for any participants that were adults. RESULTS: The mean values for lean body mass, Tanner stage, height-for-age Z score and BMI-for-age Z score were lower in the active CD group than in the inactive CD and control groups (p < 0.05 for both). Compared with the controls, the CD patients showed significant differences in terms of the quality of dietary intake (particularly in caloric intake, dietary protein intake, dietary fiber intake, and micronutrient intake), which were reflected in the serum levels of nutrients, mainly vitamins A and E (p < 0.05). CONCLUSIONS: Adolescents with CD (including those with mildly to moderately active or inactive disease) have a nutritional risk, which makes it important to conduct nutritional assessments in such patients.