Tuberculose pulmonar causada pelo uso de infliximab em paciente com Doença de Crohn / Pulmonary tuberculosis caused by the use of infliximab in a patient with Crohn's Disease

A doença de Crohn é uma patologia caracterizada pela inflamação transmural do trato gastrointestinal, compondo o espectro das doenças inflamatórias intestinais. Nos casos mais graves, dispõe de tratamento com uso de agentes biológicos e imunomoduladores que podem à reativação ou exacerbação de doenças infecciosas preexistentes. Este relato de caso trata de uma paciente do sexo feminino de 24 anos, diagnosticada com Doença de Crohn há 10 anos, evoluindo com necessidade de tratamento com infliximab e, após período de menos de 1 ano, apresentou odinofagia progressiva, dor abdominal e diarreia, além de perda ponderal, sudorese noturna e febre diária. Tomografia computadorizada de tórax evidenciou árvore em brotamento, sendo confirmado diagnóstico de tuberculose pulmonar pelo Teste Rápido Molecular no escarro e provável tuberculose laríngea e intestinal.

Crohn's disease is a pathology characterized by transmural inflammation of the gastrointestinal tract, comprising the spectrum of Inflammatory Bowel Diseases. In the most severe cases, treatment using biological agents and immunomodulators may be available, which can lead to the reactivation or exacerbation of preexisting infectious diseases. This case report is about a 24-year-old female patient, diagnosed with Crohn's disease 10 years ago, evolving in need of treatment with Infliximab and, after a period of less than 1 year, she presented progressive odynophagia, abdominal pain and diarrhea, in addition to weight loss, night sweats and daily fever. Chest computer tomography showed a tree in bud, and the diagnosis of pulmonary tuberculosis was confirmed by the Rapid Molecular Test in the sputum and probable laryngeal and intestinal tuberculosis.

Progress on clinical trials of common gastrointestinal cancer drugs in China from 2012 to 2021 / 中华肿瘤杂志

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.

Utilização da monitorização terapêutica com níveis séricos de infliximabe nas doenças inflamatórias intestinais: um algoritmo simplificado baseado em evidências / Induction therapeutic drug monitoring regimen with infliximab: a simplified evidence-based algorithm for inflammatory bowel disease

ABSTRACT Therapeutic drug monitoring (TDM) of infliximab (IFX) has been recognized as an important strategy in the management of secondary loss of response to this agent, guiding clinical decision-making in the management of inflammatory bowel diseases (IBD). Although most of the data on the application of TDM for IFX refer to the maintenance phase of treatment, many studies have associated higher drug concentrations, specially in the induction phase, with achievement of important treatment targets, such as clinical remission and mucosal healing. This brief communication aims to summarize the literature on the use of TDM during induction phase of IFX and propose application of a simplified approach which can be useful into clinical practice, aiming better outcomes to IBD patients.

RESUMO A monitorização terapêutica dos níveis séricos (Therapeutic drug monitoring - TDM) de infliximabe (IFX) é uma estratégia reconhecida na tomada de decisão clínica frente a perda de resposta secundária a esta droga no manejo das doenças inflamatórias intestinais (DII). Embora a maioria dos dados sobre a aplicação dessa estratégia para IFX se refira à fase de manutenção do tratamento, muitos estudos associaram concentrações mais altas de IFX, especialmente na fase de indução, com o alcance de importantes alvos de tratamento, como remissão clínica e cicatrização da mucosa. Este artigo visa resumir as evidências da literatura sobre o uso de níveis séricos durante a fase de indução do IFX e propor a aplicação de uma abordagem simplificada que pode ser extremamente útil na prática clínica, visando melhores resultados para os pacientes.

Fatores associados com a escolha da terapia nos pacientes com doença inflamatória intestinal no Brasil / Factors associated with patient´s preference in choosing their therapy for inflammatory bowel disease in brazil

BACKGROUND: Biological therapy and new drugs have revolutionized the treatment of inflammatory bowel disease. Ideally, the choice of medication should be a shared decision with the patient, aiming at greater satisfaction, compliance, and consequently, favorable clinical outcome. OBJECTIVE: This study aims to evaluate patient's preferences in the choice of their therapy and the factors that influence this choice. METHODS: This cross-sectional study enrolled 101 outpatients with Crohn's disease or ulcerative colitis. The inclusion criteria were age ≥18 years and no previous exposure to biological therapy. Patients' preferences were assessed through questions that addressed the preferred mode of administration (oral, subcutaneous, or intravenous) and the factors that determined the choice of medication (efficacy, medical indication, fear of medication, convenience, mode of application, and personal doctors' indication). RESULTS: The mean age was 43.6±13.5 years, 75.3% were female, and 81.2% were cases of ulcerative colitis. Regarding the mode of administration, the majority of patients preferred oral (87.1%), followed by intravenous (6.93%) and subcutaneous (5.94%) medications. The reasons were "I prefer to take it at home" (42.57%), "I have more freedom" (36.63%), "I don't like self-application" (29.70%), and "I believe it works better" (19.80%). Younger patients and patients in clinical disease activity preferred intravenous mode compared to the oral route (P<0.05). Doctor's opinion (98%) was an important factor associated with the medication choice. CONCLUSION: Oral route was the preferred mode of administration and most patients took their physician's opinion into account in their choice of medication.

RESUMO CONTEXTO: A terapia biológica e os novos medicamentos revolucionaram o tratamento da doença inflamatória intestinal. A escolha do medicamento deve ser compartilhada com o paciente, visando maior satisfação, adesão e, consequentemente, desfecho clínico favorável. OBJETIVO: Este estudo teve como objetivo avaliar as preferências do paciente na escolha de sua terapia e os fatores que influenciaram essa escolha. MÉTODOS: Este estudo transversal incluiu 101 pacientes ambulatoriais com doença de Crohn ou retocolite ulcerativa. Os critérios de inclusão foram idade ≥18 anos e nenhuma exposição prévia à terapia biológica. A preferência dos pacientes foi avaliada por meio de perguntas que abordaram o modo de administração preferido (oral, subcutâneo ou intravenoso) e os fatores que determinaram a escolha do medicamento (eficácia, indicação médica, medo da injeção, conveniência, modo de aplicação e opinião pessoal do médico). RESULTADOS: A idade média foi de 43,6±13,5 anos, 75,3% eram mulheres e 81,2% eram portadores de retocolite ulcerativa. Em relação ao modo de administração, a maioria dos pacientes preferiu os medicamentos orais (87,1%), seguidos dos endovenosos (6,93%) e subcutâneos (5,94%). Os motivos foram "prefiro aplicar em casa" (42,57%), "tenho mais liberdade com essa medicação" (36,63%), "não gosto de autoaplicação" (29,70%) e "acredito que funcione melhor" (19,80%). Pacientes jovens e pacientes em atividade clínica preferiram a via intravenosa em comparação com a via oral (P<0,05). A opinião do médico (98%) foi um fator importante associado à escolha do medicamento. CONCLUSÃO: A via oral foi preferida e a maioria dos pacientes levou em consideração a opinião do seu médico na escolha do medicamento.

Infliximab-induced remission improves physical activity in patients with active Crohn's disease

SUMMARY AIM: To compare the level of physical activity (PA), exercise capacity, and body composition before and after infliximab-induced clinical remission in patients with Crohn's disease (CD). METHODS: This prospective longitudinal study evaluated 44 adult outpatients with active CD before infliximab administration and 24 weeks after infliximab therapy. The patients were evaluated for PA in daily life, exercise capacity, muscle strength, and body composition. RESULTS: 38 (86.4%) patients achieved infliximab-induced remission at 24 weeks and presented an increment in the number of steps taken of 1092 (7440±2980 vs. 6348±3177, respectively; p=0.006). The inactive time was reduced when compared to the baseline value (454.2±106.3 vs. 427.9±97.8, respectively; p=0.033). There was no difference in the distance walked before and after infliximab therapy, while there was an increase in the fat mass index in responders to infliximab compared to the baseline (19.1±7.6 vs. 14.9±5.8; p=0.001). CONCLUSIONS: Infliximab-induced remission was shown to be effective for increasing physical activity by improving the number of steps and reducing inactive time. The maintenance of clinical remission associated with incentives to regular PA may contribute to making these patients reach an ideal level of PA.

RESUMO OBJETIVO: Comparar o nível de atividade física (AF), capacidade de exercício e composição corporal antes e após remissão clínica induzida por infliximabe em pacientes com doença de Crohn (DC). MÉTODOS: Neste estudo longitudinal prospectivo, foram envolvidos 44 pacientes ambulatoriais adultos com DC ativa avaliados antes e depois de 24 semanas de terapia com infliximabe. Os pacientes foram avaliados quanto à AF, capacidade de exercício, força muscular e composição corporal. RESULTADOS: 38(86,4%) pacientes alcançaram remissão induzida por infliximabe em 24 semanas e apresentaram aumento no número de passos de 1092 (7440±2980 vs. 6348±3177, respectivamente; p=0,006). O tempo de inatividade foi reduzido quando comparado ao basal (454,2±106,3 vs. 427,9±97,8, respectivamente; p=0,033). Não houve diferença na distância percorrida antes e após a terapia com infliximabe, enquanto houve aumento no índice de massa gorda nos respondedores ao infliximabe em comparação ao basal (19,1±7,6 vs. 14,9±5,8; p=0,001). CONCLUSÕES: A remissão induzida pelo infliximabe mostrou-se eficaz no aumento da atividade física, melhorando o número de passos e reduzindo o tempo inativo. A manutenção da remissão clínica associada a incentivos à AF regular pode contribuir para que esses pacientes atinjam um nível ideal de AF.

Type 2 myocardial infarction resulted from the left thoracic stomach

Abstract The universal definition of myocardial infarction (MI) provides five subtypes of acute myocardial infarction (AMI). We present an interesting case of a type 2 myocardial infarction caused by the dilation of the left thoracic stomach.

Octreótido de liberación prolongada para el tratamiento de hemorragia digestiva alta en Pediatría / Long-acting Release Octreotide for Pediatric Upper Gastrointestinal Bleeding

Resumen: Introducción: La hemorragia digestiva por hipertensión portal, sin alternativa de tratamiento endos- cópico o quirúrgico por localizaciones ectópicas, no identificadas del sitio de sangrado o caracterís ticas anatómicas, constituye un desafío terapéutico en Pediatría. El tratamiento habitual incluye la infusión de octreótido endovenoso. En los últimos años, la presentación de octreótido de liberación prolongada (OCT-LAR) para administración mensual intramuscular, resulta una alternativa tera péutica atractiva. Objetivo: Reportar el caso de un lactante con hemorragia digestiva por hiperten sión portal que recibió tratamiento exitoso con OCT-LAR. Caso Clínico: Paciente de 8 meses de vida, con malformación de vena porta extrahepática y episodios reiterados de sangrados digestivos con re querimientos transfusionales e infusiones de octréotido, sin posibilidad de tratamiento endoscópico o quirúrgico. Indicamos OCT-LAR intramuscular mensualmente. Después de diez meses de iniciado el tratamiento, el paciente no repitió sangrados digestivos y no presentó efectos adversos relacionados a la medicación. Conclusión: Consideramos que el reporte de este caso puede resultar de utilidad al presentar una nueva alternativa para el tratamiento de pacientes pediátricos con sangrado digestivo por hipertensión portal sin posibilidades terapéuticas convencionales.

Abstract: Introduction: Upper gastrointestinal bleeding (UGIB) secondary to portal hypertension (PHT), without endoscopic or surgical treatment options due to an ectopic or unidentified bleeding site or the patient's anatomic characteristics, is challenging in pediatric hepatology. The usual treatment in these cases includes intravenous Octreotide. Recently, the availability of long-acting release Octreo tide (OCT-LAR) for monthly intramuscular administration has become an interesting therapeutic alternative. Objective: To report the case of an infant with UGIB due to PHT who was successfully treated with OCT-LAR. Clinical Case: Eight-month-old patient with repeated episodes of UGIB due to extrahepatic portal vein malformation, requiring blood transfusions, and intravenous octreotide infusions. As neither endoscopic nor surgical treatment were feasible, we decided to start IM OCT- LAR monthly. After ten months of treatment, the patient did not present bleeding episodes. No medication-related events were observed. Conclusion: We consider that this report could help in the management of similar pediatric patients with UGIB due to PHT without conventional therapeutic possibilities.

Pérdida de respuesta a terapia anti-TNF en enfermedad inflamatoria intestinal: experiencia en un hospital de referencia en Lima - Perú / Loss of response to anti-TNF therapy in inflammatory bowel disease: experience in a reference hospital in Lima - Peru

RESUMEN Objetivo: Evaluar la respuesta al tratamiento con anti-TNFs en pacientes con enfermedad inflamatoria intestinal. Materiales y métodos: Estudio prospectivo observacional realizado en el Servicio de Gastroenterología del Hospital Nacional Guillermo Almenara, de enero 2015 a agosto 2018. Resultados: Se evaluó 31 pacientes con enfermedad inflamatoria intestinal que recibían terapia de mantenimiento con Infliximab. Doce (38,7%) pacientes (3 con colitis ulcerativa y 9 con enfermedad de Crohn) presentaron pérdida de respuesta a partir de los 6 meses del inicio de la fase de mantenimiento: 2 entre 6-12 meses, 4 entre 12-18 meses y 6 entre 18-24 meses. Como primera medida se duplicó la dosis (10 mg/kg) a los 12 pacientes, obteniendo respuesta en 6 (50%) luego de 12 semanas. De los 6 pacientes restantes, 4 cambiaron a Adalimumab, 1 paciente presentó cáncer de colon y 1 paciente presentó anafilaxia y sarcoidosis. De los pacientes que recibieron Adalimumab, 3 presentaron recidiva endoscópica (75%) a partir de los 6 meses y 1 no respondió a la terapia de inducción y fue sometido a colectomía (25%). Conclusiones: Aproximadamente un tercio de nuestros pacientes presentó pérdida de respuesta a terapia de mantenimiento con Infliximab. El escalamiento de dosis como rescate tuvo éxito en la mitad de los pacientes. El cambio a Adalimumab en pacientes con pérdida de respuesta a un primer fármaco anti-TNF no parece ser efectivo.

ABSTRACT Objective: To evaluate the response to treatment with anti-TNFs in patients with inflammatory bowel disease. Materials and methods: Prospective observational study conducted in the Gastroenterology service of the Guillermo Almenara National Hospital, from January 2015 to August 2018. Results: 31 patients with inflammatory bowel disease who received maintenance therapy with Infliximab were evaluated. Twelve (38.7%) patients (3 with ulcerative colitis and 9 with Crohn's disease) presented loss of response after 6 months of the beginning of the maintenance phase: 2 between 6-12 months, 4 between 12-18 months and 6 between 1824 months. As a first step, the dose was doubled (10 mg/kg) to the 12 patients, obtaining a response in 6 (50%) after 12 weeks. Of the remaining 6 patients, 4 switched to Adalimumab, 1 patient presented colon cancer and 1 patient presented anaphylaxis and sarcoidosis. Of the patients who received Adalimumab, 3 had endoscopic recurrence (75%) after 6 months and 1 did not respond to induction therapy and was subjected to colectomy (25%). Conclusions: Approximately one third of our patients presented loss of response to maintenance therapy with Infliximab. The dose escalation as a rescue therapy was successful in half of the patients. The change to Adalimumab in patients with loss of response to a first anti-TNF drug does not seem to be effective.

Aspectos clínicos relacionados con el Síndrome Respiratorio Agudo Severo (SARS-CoV-2) / Clinical aspects related to the Severe acute respiratory syndrome (SARS-CoV-2)

Introducción: El nuevo coronavirus 2019 (2019nCoV) puede causar enfermedades tanto en animales como en humanos. Objetivo: Describir algunas características del comportamiento clínico del COVID-19 en personas afectadas por esta enfermedad. Material y Métodos: Se realizó una búsqueda de literatura relevante sobre el tema en el primer trimestre de 2020. Se utilizaron como buscadores de información científica a Pubmed, Google y Google Académico. Como criterios de elegibilidad, se evaluaron artículos de revisión, investigación y páginas Web que, en general, tenían menos de 5 años de publicados. Esto permitió el estudio de 60 artículos, de los cuales 43 fueron referenciados. Desarrollo: La COVID-19 es una enfermedad zoonótica ocasionada por un nuevo β-coronavirus y su evolución en forma de una pandemia, afecta más al sexo masculino y a personas con ciertas comorbilidades. La mayoría de los casos ocurre aproximadamente entre 3 a 7 días después de la exposición, aunque en algunas personas puede tardar hasta 14 días para que aparezcan los síntomas. Puede incluir fiebre, secreción nasal, dolor de garganta, tos, fatiga, dolores musculares, dificultad respiratoria, expectoración, hemoptisis, y diarrea. La enfermedad, se puede expresar con un cuadro clínico de manifestaciones muy leves a extremadamente graves, que incluso puede causar la muerte. Conclusiones: La COVID-19 ha sido responsable de una importante morbilidad y mortalidad en todo el mundo, sobre todo en los adultos y su comportamiento clínico incluye síntomas y signos respiratorios, generales y digestivos. El desenlace fatal es más común en personas que tienen otros problemas de salud(AU)

Introduction: The 2019 novel coronavirus (2019-nCoV) can cause diseases in both animals and humans. Objective: To describe some characteristics of the clinical behavior of COVID-19 in people affected by this disease. Material and Methods: A search for relevant literature on the subject was carried out in the first quarter of 2020. Pubmed, Google and Google Scholar were used as search engines to locate scientific information. As eligibility criteria, review articles, research articles and web pages that, in general, were less than 5 years old, were evaluated. This allowed the study of 60 articles, of which 43 were referenced. Development: COVID-19 is a zoonotic disease caused by a new β-coronavirus and its evolution in the form of a pandemic, affects more males and people with certain comorbidities. Most cases occur approximately from 3 to 7 days after exposure, although in some people it can take up to 14 days for symptoms to appear. The symptoms can include fever, runny nose, sore throat, cough, fatigue, muscle aches, shortness of breath, expectoration, hemoptysis, and diarrhea. The disease can be expressed with a clinical picture from very mild to extremely serious manifestations, which can even cause death. Conclusions: COVID-19 has been responsible for significant morbidity and mortality worldwide, especially in adults. Its clinical behavior includes respiratory, general, and digestive symptoms and signs. The fatal outcome is more common in people who have other health problems(AU)

The impact of small intestinal bacterial overgrowth on the growth of children and adolescents / Impacto do sobrecrescimento bacteriano no intestino delgado sobre o peso e a estatura de crianças e adolescentes

ABSTRACT Objective: To evaluate the association between small intestinal bacterial overgrowth (SIBO) and weight and height impairment in children and adolescents with gastroenterology diseases. Methods: Observational and retrospective study. All 162 patients aged less than 19 years old who underwent breath test in search of SIBO between 2011 and 2016 were studied. Breath test was collected after the intake of 10 grams of lactulose. The concentration of hydrogen and methane was measured for 180 minutes after the beginning of the test by 12i QuinTronMicroLyzer device. Results: SIBO was identified in 51 (31.5%) patients. There was no difference between the age of those with (mean=8.7y.o; 25th and 75th percentile: 4.6 and 11.3) and without (mean=7.9y.o 25th and 75th percentile: 4.8 and 12.2) SIBO (p=0.910). There was no association between gender and SIBO (male 26.3% vs. female 36.3%, p=1.00). A lower median of height-for-age Z score (mean=-1.32; 25th and 75th percentile: -2.12 and -0.08 vs. mean=-0.59; 25th and 75th percentile: -1.57 and 0.22; p=0.04) was demonstrated in children with SIBO when compared with children without it. There was no difference between the BMI-for-age Z score of patients with (mean=-0.48) and without SIBO (mean=-0.06) (p=0.106). The BMI of patients with SIBO (median=15.39) was lower than of those without it (median=16.06); however, the statistical analysis was not significant (p=0.052). The weight-for-age Z score was lower in patients with SIBO (mean=-0.96) than in those without SIBO (mean=-0.22) (p=0.02) Conclusions: Children and adolescents with SBIO associated with diseases of the gastrointestinal tract have lower weight and height values.

RESUMO Objetivo: Avaliar a existência de associação entre sobrecrescimento bacteriano no intestino delgado (SBID) e comprometimento de peso e estatura em crianças e adolescentes com doenças do aparelho digestivo. Métodos: Estudo observacional e retrospectivo em ambulatório de gastroenterologia pediátrica. Foram incluídos todos os 162 pacientes com idade inferior a 19 anos que realizaram teste respiratório para pesquisa de SBID entre 2011 e 2016. O teste respiratório foi realizado após ingestão de dez gramas de lactulose. Foram determinadas as concentrações de hidrogênio e metano em aparelho 12i QuinTron MicroLyzer até 180 minutos após o início do teste respiratório. Resultados: SBID foi caracterizado em 51 (31,5%) dos 162 pacientes. Não houve diferença na idade das crianças com (mediana=8,7 anos; percentil 25-75: 4,6-11,3) e sem (mediana=7,9 anos; percentil 25-75: 4,8-12,2) SBID (p=0,910). Não se observou associação entre SBID e sexo (masculino 27,4% e feminino 36,6%; p=0,283). O escore Z da estatura-idade nos pacientes com SBID (mediana=-1,32; percentil 25-75: -2,12—0,08) foi menor (p=0,040) do que naqueles sem SBID (mediana=-0,59; percentil 25-75: -1,57-0,22). Na comparação do escore Z de índice de massa corpórea-idade não foi observada diferença entre os grupos com (média=-0,489±1,528) e sem (média=-0,067±1,532) SBID (p=0,106). Nos pacientes com menos de 10 anos de idade, o escore Z de peso-idade foi menor nos pacientes com SBID (média=-0,968±1,359) do que nos sem SBID (média=-0,223±1,584) (p=0,026). Conclusões: Crianças e adolescentes com SBID associado a doenças do trato gastrintestinal apresentam menores valores de peso e estatura.

Neutrophil-lymphocyte ratio at 14th week predicts loss of response to 52-week infliximab therapy in patients with Crohn's disease / 南方医科大学学报

OBJECTIVE@#Loss of response (LOR) has become an important clinical problem in patients with Crohn's disease receiving infliximab (IFX) treatment. Neutrophil-lymphocyte ratio (NLR) has been shown to correlate with the activity of inflammatory bowel disease (IBD), and NLR at the 14th week of IFX therapy potentially allows the prediction of sustained response to IFX in Crohn's patients. The aim of this study was to explore whether NLR at the 14th week of IFX therapy could predict the occurrence of LOR to IFX in Crohn's patients.@*METHODS@#Between January, 2012 and December, 2016, 54 patients with Crohn's disease underwent a 52-week treatment with IFX and successfully achieved response to the induction treatment in Zhongnan Hospital. We retrospectively examined their medical records and assessed the association between NLR at 14 weeks and LOR during IFX therapy.@*RESULTS@#Of the 54 patients, 15 (27.8%) showed LOR to IFX during the follow-up. We noted a significant increase in NLR at 14 weeks in the patients with LOR as compared with the patients with sustained response to IFX[3.51 (2.9-6.25) 1.77 (1.23-2.56), =0.00]. Receiver-operating characteristic analysis showed that at the cut-off value of 2.75, NLR at 14 weeks was predictive of LOR within 52 weeks of IFX therapy with a sensitivity of 93.33% and a specificity of 84.62%, and the area under curve (AUC) of NLR was 0.903 (0.731-0.959). Univariate analysis revealed a significant correlation between relapse-free survival and the NLR at 14 weeks (=0.00). Multivariate analysis identified NLR at 14 weeks as an independent prognostic factor for LOR with a hazard ratio of 1.851 (95% :1.096-3.026, =0.021).@*CONCLUSIONS@#NLR at the 14th week during IFX therapy is a useful predictor for LOR in patients with Crohn's disease.

Effects of anti-TNF-α in experimental diversion colitis

Abstract Purpose: To evaluate the effects of infliximab on the inflammation of the colonic mucosa devoid from fecal stream. Methods: Twenty-four rats were submitted to a Hartmann's procedure. They remained for 12 weeks with the fecal derivation to development of diversion colitis on excluded colorectal stump. After this period, they were divided into 3 groups: one group received intervention with saline (2.0 mL / week), other group infliximab at doses of 5 mg/kg/week and the other 10 mg/kg/week for five consecutively weeks. Concluded the intervention period, the animals were euthanized to remove colon segments with and without fecal stream. Colitis was diagnosed by histological analysis and the degree of inflammation by validated score. The neutrophilic infiltrate was evaluated by tissue expression of myeloperoxidase identified by immunohistochemical. The tissue content of myeloperoxidase was measured by computer-assisted image analysis. Results: The inflammatory score was high in colonic segments without fecal stream. The intervention with infliximab reduced the inflammatory score in excluded colonic segments. The content of myeloperoxidase was reduced in colonic segments of animals treated with infliximab mainly in high concentrations. Conclusion: Intervention with infliximab reduced the inflammation and the neutrophil infiltrate in colonic segments devoid of the fecal stream.

Sarcopenia e gravidade da doença hepática gordurosa não-alcoólica / Sarcopenia and severity of non-alcoholic fatty liver disease

ABSTRACT BACKGROUND: Non-alcoholic fatty liver disease is characterized by deposition of lipids in the hepatic parenchyma exceeding 5% of liver weight in the absence of other conditions, such as viral or alcoholic hepatitis and metabolic disease. Non-alcoholic fatty liver disease is the most common form of chronic liver disease in several countries. In addition to liver complications, recent studies have shown a relation between liver fat and sarcopenia. OBJECTIVE: Determine the association between sarcopenia and the severity of non-alcoholic hepatic steatosis diagnosed by abdominal ultrasonography. METHODS: A clinical, cross-sectional study was conducted with a sample of male and female adults (18 to 70 years of age) submitted to ultrasonography for the investigation of non-alcoholic hepatic steatosis. Evaluations were also performed for the determination of upper and lower limb muscle strength. Data analysis was performed with the aid of the SPSS 22.0 program and involved ANCOVA and the Bonferroni post hoc test, with P-value <0.05 considered indicative of statistical significance. RESULTS: One hundred two patients were submitted to abdominal ultrasonography, 57.8% of whom presented some degree of non-alcoholic hepatic steatosis. The presence and degree of fatty liver infiltration were significantly associated with the sarcopenic index, determined by the ratio between upper and lower limb strength and BMI (P=0.009 and post-test P=0.028 for upper limbs; P=0.006 and post-test P=0.013 for lower limbs). CONCLUSION: In the present study, an association was found between the sarcopenic index and non-alcoholic hepatic steatosis, with an inversely proportional relation between this index and the severity of fatty infiltration. This finding offers further evidence of the metabolic interaction of the liver, adipose tissue and muscle.

RESUMO CONTEXTO: A doença hepática gordura não-alcoólica caracteriza-se pela deposição de lipídios no parênquima hepático, excedendo 5% do peso do fígado na ausência de outras afecções como hepatites virais, alcoólicas ou doenças metabólicas. A doença hepática gordura não-alcoólica tem sido observada como a forma mais comum de doença hepática crônica em diversos países. Além das complicações hepáticas, estudos recentes têm demonstrado a relação entre a presença de gordura hepática e a sarcopenia. OBJETIVO: Determinar a associação entre a sarcopenia e a gravidade da esteatose hepática não-alcoólica diagnosticada pela ultrassonografia abdominal. MÉTODOS: Estudo clínico e transversal com amostra de pacientes de ambos os sexos, de 18 a 70 anos de idade, diagnosticados como portadores ou não de esteatose hepática não-alcoólica pela ultrassonografia e submetidos à avaliação da força muscular dos membros superiores e inferiores. Os dados foram inseridos no programa estatístico SPSS 22.0, analisados através do teste ANCOVA e pós-teste de Bonferroni, sendo considerado significante P<0,05. RESULTADOS: Foram avaliados pela ultrassonografia abdominal 102 pacientes e destes, 57,8% apresentaram algum grau de esteatose hepática não-alcoólica. A presença e os graus da infiltração gordurosa no fígado tiveram associação estatisticamente significativa com o índice sarcopênico, determinado pela razão entre força muscular dos membros superiores e inferiores e o IMC (P=0,009 e pós-teste P=0,028 MMSS; P=0,006 e pós-teste P=0,013 MMII). CONCLUSÃO: Observou-se associação entre o índice sarcopênico e a presença de esteatose hepática não-alcoólica, com relação inversamente proporcional entre esse índice e a gravidade da infiltração gordurosa, reforçando a interação do eixo metabólico entre fígado, tecido adiposo e músculo.

Atividade física de vida diária, capacidade de exercício e qualidade de vida de pacientes com doença de Crohn em remissão induzida por infliximabe: um estudo preliminar / Physical activity in daily life, exercise capacity and quality of life in patients with crohn's disease on infliximab-induced remission: a preliminary study

ABSTRACT BACKGROUND: Physical activity in daily life and exercise capacity have not been assessed in patients with Crohn's disease to date. OBJECTIVE: To evaluate the physical activity in daily life, exercise capacity, quality of life, and prevalence of mood disorders in patients with moderate-to-severe Crohn's disease on infliximab-induced remission and the possible associations among variables. METHODS: A cross-sectional preliminary study was conducted. Twenty-six patients with Crohn's disease and 20 controls were selected. Participants underwent evaluation of physical activity in daily life (triaxial accelerometer), exercise capacity (shuttle walk test), handgrip strength, quality of life, and presence of mood disorders. RESULTS: The number of steps taken (7446±3081 vs 7898±2487), active time (80.6±42 vs 89.7±24.3min), shuttle walk test distance [665 (405) vs 710 (409) m] and handgrip strength [31 (15) vs 29 (20) kgf did not show any difference between the patients with Crohn's disease and the controls. The time spent lying down [95.8 (68.8) vs 60.9 (74.7) min] was greater and some domains of the quality of life were superior in the patients with Crohn's disease. No correlation was observed between the physical activity in daily life and quality of life or presence of mood disorders in patients with Crohn's disease. CONCLUSION: Patients with Crohn's disease on infliximab-induced remission, despite to more time spent lying down, they have the same level of physical activity in daily life and exercise capacity min compared with the controls.

RESUMO CONTEXTO: A atividade física na vida diária e a capacidade de exercício não tem sido avaliada em pacientes com doença de Crohn. OBJETIVO: Avaliar a atividade física na vida diária, capacidade de exercício, qualidade de vida e distúrbios de humor em pacientes com doença de Crohn moderada-grave em remissão induzida pelo infliximabe, e as possíveis associações entre essas variáveis. MÉTODOS: Este foi um estudo preliminar transversal, envolvendo 26 pacientes com doença de Crohn e 20 controles. Os participantes realizaram as seguintes avaliações: atividade física na vida diária por meio de um acelerômetro triaxial, capacidade de exercício (teste de Shuttle), força de preensão palmar, qualidade de vida e distúrbios do humor. RESULTADOS: O número de passos registrados (7446±3081 vs 7898±2487), o tempo ativo (80,6±42,0 vs 89,7±24,3min), a distância caminhada no teste de Shuttle 665 (405) vs 710 (409) m, e a força de preensão manual 31(15) vs 29 (20) kgf não mostraram diferenças entre os pacientes com doença de Crohn e os controles, respectivamente. O tempo gasto na posição deitada 95.8 (68.8) vs 60.9 (74.7) min, e alguns domínios da qualidade de vida foram maiores nos pacientes com doença de Crohn. Nenhuma correlação foi observada entre a atividade física na vida diária e a qualidade de vida ou distúrbios do humor nos pacientes com doença de Crohn. CONCLUSÃO: Pacientes com doença de Crohn em remissão induzida por infliximabe, apesar de passarem mais tempo deitados, apresentam mesmo nível de atividade física e capacidade de exercício quando comparados aos controles.

Vedolizumabe no manejo das doenças inflamatórias intestinais: um estudo multicentrico observacional brasileiro / Vedolizumab in the management of inflammatory bowel diseases: a brazilian observational multicentric study

ABSTRACT BACKGROUND: There is scarce data regarding efficacy and safety of vedolizumab in inflammatory bowel diseases in Latin America. OBJECTIVE: To describe the first observational real-world experience with vedolizumab in Latin American inflammatory bowel diseases patients. METHODS: Retrospective observational multicentric study of patients with Crohn's disease (CD) and ulcerative colitis (UC) who used vedolizumab at any phase of their treatment. Clinical remission and response (according to Harvey-Bradshaw index for CD and Mayo score for UC), mucosal healing, need for surgery and adverse events were evaluated. RESULTS: A total of 90 patients were included (52 with CD and 38 with UC), the majority with previous exposure to anti-TNF agents (88.46% in CD and 76.31% in UC). In CD (as observed analysis) remission rates at weeks 12, 26 and 52 were 42.89% (21/49), 61.9% (26/42) and 46.15% (12/26), respectively. In UC, remission rates at weeks 12, 26 and 52 were 28.94% (11/38), 36.66% (11/30) and 41.17% (7/17). Mucosal healing rates were 36.11% in CD and 43.4% in UC. During the study period, 7/52 CD patients underwent major abdominal surgery and 4/38 UC patients needed colectomy. CONCLUSION: Vedolizumab was effective in induction and maintenance of clinical response and remission in CD and UC, with no new safety signs.

RESUMO CONTEXTO: Há escassez de dados sobre a eficácia e segurança do vedolizumabe nas doenças inflamatórias intestinais na América Latina. OBJETIVO: Descrever a primeira experiência observacional de mundo real com vedolizumabe em pacientes latino-americanos com doenças inflamatórias intestinais. MÉTODOS: Estudo retrospectivo multicêntrico observacional de pacientes com doença de Crohn (DC) e retocolite ulcerativa inespecífica (RCUI) que utilizaram vedolizumabe em qualquer fase de seu tratamento. Foram avaliadas a remissão e resposta clínicas (de acordo com o índice de Harvey-Bradshaw para DC e escore de Mayo para RCUI), cicatrização da mucosa, necessidade de cirurgia e eventos adversos. RESULTADOS: Foram incluídos 90 pacientes (52 com DC e 38 com RCUI), a maioria com exposição prévia a agentes anti-TNF (88,46% na DC e 76,31% na RCUI). Na DC (em análise conforme observado), as taxas de remissão nas semanas 12, 26 e 52 foram 42,89% (21/49), 61,9% (26/42) e 46,15% (12/26), respectivamente. Na RCUI, as taxas de remissão nas semanas 12, 26 e 52 foram de 28,94% (11/38), 36,66% (11/30) e 41,17% (7/17). As taxas de cicatrização da mucosa foram 36,11% na DC e 43,4% na RCUI. Durante o período do estudo, 7/52 pacientes com DC foram submetidos a cirurgia abdominal maior e 4/38 pacientes com RCUI necessitaram de colectomia. CONCLUSÃO: O vedolizumabe foi eficaz na indução e manutenção da resposta e remissão clínicas em população refratária na DC e RCUI, com perfil de segurança favorável.

Terapia biológica na doença de Crohn: quando iniciar? / Biologic therapy for Crohn's disease: when to initiate?

A doença de Crohn se caracteriza como uma doença inflamatória, que acomete qualquer porção do trato gastrintestinal, resultante da desrregulação imunológica, gerenciada por fatores endógenos e exógenos. As formas de abordagem terapêutica da doença variam conforme sua apresentação clínica e gravidade, bem como o impacto na qualidade de vida do portador. A terapia biológica vem se tornando uma das principais classes utilizadas no contexto desta enfermidade, mas não está claro quando deve ser iniciada ou em que momento a própria doença deve ser considerada moderada ou grave. Sua forma de apresentação multiforme dificulta a classificação dos pacientes nestes grupos. Neste trabalho, foi realizada revisão de literatura sobre a introdução de terapia biológica como tratamento da doença inflamatória intestinal em curso. (AU)

Crohn's Disease (CD) is an inflammatory disease that can affect any portion of the gastrointestinal tract, caused by immune dysregulation, managed by endogenous and exogenous factors. The forms of therapeutic approach of the disease vary significantly according to its clinical presentation and severity, as well as to the impact on patient's quality of life. Biologic therapy has become one of the main classes used in the context of this disease; however, when it should be initiated or at what time the disease itself should be considered moderate or severe is not clear. Its multiform presentation makes it difficult to classify patients in these groups. In this work, a literature review was carried out about the introduction of the biologic therapy as a treatment of the ongoing inflammatory bowel disease. (AU)

Complicaciones de la colonoscopia en pacientes de la tercera edad / Complications of colonoscopy in elderly patients

Antecedentes: la OMS define a todo individuo mayor de 60 años como persona de la tercera edad. Existen 3 grupos: edad avanzada (60-74 años), ancianos o viejos (75-90 años) y grandes ancianos o longevos (mayor de 90 años). Se señala un riesgo mayor en mayores de 80 años cuando se realiza una colonoscopia como método para diagnóstico o seguimiento del cáncer colorrectal. Objetivo: analizar la morbilidad según la edad de pacientes sometidos a colonoscopias. Material y métodos: se registraron todas las complicaciones a 30 días de realizada la endoscopia. Las complicaciones fueron eventos digestivos (perforación, sangrado, transfusiones, distensión, náuseas, vómitos, dolor abdominal) y no digestivos (deshidratación, infarto, ángor, otros). Se usó prueba de relaciones y proporciones y exacta de Fisher con corrección de Yates y chi cuadrado según el tipo de variable, considerando significativo p<0,05. Resultados: se registraron 11 746 colonoscopias y analizaron 11 042 (pérdida seguimiento de 704). Hubo 239 pacientes mayores de 80 años, 4070 entre 60 y 80 y 7437 menores de 60. El 57,8% fueron diagnósticas (6800), 2222 en mayores de 60 con un 99% de procedimientos ambulatorios. Se interrumpieron 15 procedimientos por intolerancia a la anestesia. Se registró una fibrilación auricular sin traducción clínica con reversión posterior. No hubo evento clínico mayor. Se registraron 14 complicaciones (0,12%), 6 en procedimientos terapéuticos (0,05%). No hubo morbimortalidad de relevancia asociada. Conclusiones: las complicaciones luego de una colonoscopia son escasas. Los estudios que hablan de un mayor riesgo en mayores de 60 años son discutibles. La prevención mediante colonoscopia es primordial y no tiene más complicaciones que en la población general en mayores de 60 años y es muy segura en mayores de 80 años en nuestra experiencia.

Background: For the World Health organization, elderly persons are those > 60 years, and classifies this age group in three sub-groups: the elderly (60-74 years), the old (75-90 years) and the long-lived (> 90 years). Patients > 80 years undergoing a colonoscopy for diagnosis or follow-up of colorectal cancer are believed to be at higher risk of complications. Objective: The aim of this study is to analyze the incidence of complications of colonoscopy by age. Material and methods: We conducted a retrospective analysis of a consecutive series of adult patients undergoing colonoscopy in three institutions between January 2005 and June 2017. All the complications occurring within 30 days of the procedure were recorded. Gastrointestinal complications included perforation, bleeding, transfusions, bloating, nausea, vomiting and abdominal pain. Dehydration, myocardial infarction and angina were non-gastrointestinal complications. The variables were compared using the Fisher's exact test with Yates correction or the chi square test, as applicable. A p 80 years, 4070 between 60 and 80 years and 7437 60 years and 99% were outpatient procedures. Fifteen procedures were cancelled due to intolerance to anesthesia. One patient presented atrial fibrillation with no clinical relevance. There were no major adverse events. Complications occurred in 14 patients (0.12%), 6 in therapeutic procedure (0.05%), There were significant morbidity or mortality associated. Conclusions: Complications after colonoscopy are rare. The higher risk reported in > 60 years is controversial. Screening for colorectal cancer is essential and the incidence of colonoscopy-related complications in > 60 years is similar to that of the general population. Colonoscopy is a safe procedure in patients > 80 years.