Efectos del ejercicio en enfermedades del tubo digestivo / The effects of excercise on gastrointestinal diseases

Actualmente, existe una mayor evidencia acerca de los efectos positivos de la actividad física, y en especial del ejercicio, sobre algunas enfermedades del sistema gastrointestinal, lo cual tiene relación principalmente con su rol antiinflamatorio a nivel sistémico. Sin embargo, es necesario considerar algunas variables del ejercicio, tales como el volumen e intensidad de éste. Específicamente, el realizar ejercicios de larga duración y alta intensidad, asociados a estados de deshidratación, postprandiales y con altas temperaturas ambientales, podría contribuir a la expresión fisiológica del síndrome gastrointestinal inducido por el ejercicio y a la aparición y/o empeoramiento de los síntomas en las enfermedades del tracto gastrointestinal. Si se controlan dichas variables, realizar ejercicio aeróbico de moderada intensidad y, adicionalmente, durante menos de 60 minutos, serían seguros para disminuir el riesgo y controlar de mejor manera los síntomas de algunas patologías gastrointestinales.

Currently, there is an increase evidence about the beneficial effects of physical activity, particularly of physical exercise in some diseases of the gastrointestinal system, related to its systemic anti-inflammatory role. However, it is necessary to consider some of the exercise variables such as volume and exercise intensity. Specifically, the execution of long duration and high intensity exercises, together with a state of dehydration, postprandial and high environmental temperature, could contribute to the physiological expression of the exercise-induced gastrointestinal syndrome and the expression and/or worsening of gastrointestinal diseases symptoms.

Tofacitinib en el tratamiento de la colitis ulcerosa: casos clínicos / Tofacitinib for the treatment of ulcerative colitis: report of two cases

Biological therapy dramatically changed the management of Ulcerative Colitis (UC). However, a significant number of these patients fail to respond or have secondary loss of response to this strategy. In this clinical situation, the options include intensification of anti-TNF therapy, the use of a second anti-TNF or being switched to another drug class. Among the later, tofacitinib, an oral small molecule directed against the JAK/STAT pathway, is safe and effective in inducing and maintaining remission in patients with moderate-severe UC. We report two patients with UC refractory to conventional treatment and biological therapy, who responded successfully to the use of tofacitinib.

Factores ambientales en el desarrollo y evolución de la enfermedad inflamatoria intestinal / Environmental risk factors in the development and evolution of inflammatory bowel disease

Environmental factors may influence the development of Inflammatory Bowel Disease and modify its natural history. The objective of this review is to evaluate current evidence about environmental factors associated with the disease. A better knowledge about the pathogenesis of the disease can lead to better treatment strategies and suggestions to prevent the disease.

Utilidad de la monitorización terapéutica de infliximab en el manejo de la enfermedad inflamatoria intestinal / Usefulness of therapeutic monitoring of infliximab in the treatment of inflammatory bowel disease

Background: Primary non-response and secondary loss of response (LOR) are significant problems of biological therapy for inflammatory bowel disease (IBD). Therapeutic drug monitoring (TDM) in IBD patients receiving these drugs can improve outcomes. Aim: To measure serum infliximab levels and anti-infliximab antibodies (ATI) in patients with IBD post-induction phase and during maintenance therapy assessing the clinical course of IBD. Patients and Methods: Prospective study of IBD patients receiving infliximab between July 2016-May 2017. Group-A included patients who received induction therapy while Group-B included patients who were in maintenance therapy. TDM was performed in serum samples collected at weeks-14 and 30 in Group-A and before the infliximab maintenance dose in Group-B. Clinical scores, fecal calprotectin and endoscopic score were also evaluated. Results: Of 14 patients in Group-A, 57% achieved endoscopic response. Median serum infliximab concentrations at week-14 and 30 were 2.65 AU/mL (0.23-32.58) and 2.3 AU/mL (0.3-16.8), respectively. Patients with mucosal healing had non-significantly higher median infliximab concentrations at week- 14, as compared to week 30 (median 3.2 vs 2.2 AU/ml, respectively, p 0.6). ATI >10 ug/mL were found in one and seven patients at week-14 and 30, respectively. At 52 weeks of follow-up, four patients (31%) had LOR. Group-B included 36 patients, 33% had LOR. Median serum concentrations of infliximab were 1.4 AU/mL (0.27-7.03). No significant differences in serum infliximab concentration were observed between patients in remission and those with inflammatory activity. Seventeen patients had ATI >10 ug/mL. Conclusions: Clinical algorithms using TDM might help to optimize the pharmacological therapy of IBD.

Experiencia del trasplante de microbiota fecal a través de colonoscopía en el tratamiento de la infección por Clostridium difficile recurrente / Fecal microbiota transplantation through colonoscopy for Clostridium difficile recurrent infection: report of eight cases

Background: Most cases of Clostridium difficile infection (CDI) respond to a standard course of antibiotics, however recurrent CDI is becoming common and alternative therapeutic strategies are needed. In this scenario, fecal microbiota transplantation (FMT) has been suggested. Aim: To describe the efficacy and safety of FMT for the treatment of recurrent CDI. Patients and Methods: Review of medical records of all patients with recurrent CDI treated with FMT between April 2013 and April 2017. Demographic and clinical data were abstracted including details of treatment prior to FMT, rate of FMT treatment success and clinical course during follow-up period. Telephone surveys were conducted to determine patient satisfaction. Results: Eight patients aged 19 to 82 years (six women) underwent FMT. They experienced a median of four previous episodes of CDI (range 3-8). The mean duration of CDI was 18 days (range 3-36) before FMT. All procedures were performed by colonoscopy. Effectiveness with one session of FMT was 100%. During the follow-up period (median 24 months, range 7-55), two patients developed CDI, one of them after using antibiotics. Adverse events were reported in three patients. Two had bloating and one patient with Crohn's disease and a history of bacteremia had an episode of Escherichia coli bacteremia. All patients would use FMT again if necessary. Conclusions: FMT through colonoscopy appears to be a safe, effective and long-lasting therapy in cases of recurrent CDI.

Terapia de inducción acelerada con infliximab en paciente con colitis ulcerosa grave refractaria a corticoides: caso clínico / Acute severe ulcerative colitis treated with accelerated infliximab induction: case report

Acute severe ulcerative colitis (ASUC) is a potentially life-threatening condition that requires early recognition, hospitalization and adequate treatment. Currently, the use of infliximab in ulcerative colitis (UC) is recommended in the case of severe disease refractory to corticosteroids, once that superimposed bacterial or viral infections (such as cytomegalovirus or Clostridium difficile) have been excluded. However, conventional weight-based regimens of infliximab might be insufficient for patients with ASUC. Accelerated infliximab induction regimen may increase its serum concentration levels and efficacy by reducing early colectomy rates in these patients. We report a 34 year old female presenting with an ASUC. She was initially treated with hydrocortisone 300 mg/day and mesalazine enemas 4 g/day with an unfavorable clinical response. At the fifth day of therapy, an accelerated induction therapy with infliximab was started in doses of 10 mg/kg at weeks 0, 1 and 4. After the second dose, there was a favorable response with reduction of abdominal pain, stool frequency and hematochezia. She was discharged with prednisone and azathioprine. After a year of starting infliximab, the patient remains in clinical remission.

Experiencia local con natalizumab en pacientes con enfermedad de Crohn refractaria a anti-TNF: casos clínicos / Natalizumab for the treatment of Crohns disease: report of three cases

Anti-tumor necrosis factor-α (TNF) agents have dramatically changed the management of Crohn’s Disease (CD). However, a significant number of these patients do not respond at all or cease to respond to antibodies against TNF. In this clinical situation, the options include intensification of anti-TNF therapy by either increasing the dose or by shortening the administration interval, the use of a second anti-TNF or medications with a different mechanism of action. Among the later, Natalizumab, a humanized IgG4 monoclonal antibody against α4β1 and α4β7 integrins, is safe and effective in inducing and maintaining remission in active CD patient’s refractory to anti-TNF. In spite of this, Natalizumab use has been limited because of an increased risk of progressive multifocal leukoencephalophaty which results from reactivation of the John Cunningham (JC) virus. However, the presence of antibodies against JC virus in serum can be used to reduce the risk for this complication. We report three patients with Crohn’s disease refractory to treatment with infliximab, who responded successfully to the use of Natalizumab.

Diagnóstico y manejo de colitis ulcerosa grave: una mirada actualizada / Management of severe ulcerative colitis: an up-to-date

Ulcerative Colitis (UC) is a chronic inflammatory disease involving the colon, with alternating periods of remission and activity. Exacerbations can be severe and associated with complications and mortality. Diagnosis of severe UC is based on clinical, biochemical and endoscopic variables. Patients with severe UC must be hospitalized. First line therapy is the use of intravenous corticoids which achieve clinical remission in most patients. However, 25% of patients will be refractory to corticoids, situation that should be evaluated at the third day of therapy. In patients without response, cytomegalovirus infection must be quickly ruled out to escalate to second line therapy with biological drugs or cyclosporine. Total colectomy must not be delayed if there is no response to second line therapy, if there is a contraindication for second line therapies or there are complications such as: megacolon, perforation or massive bleeding. An active management with quick escalation on therapy allows to decrease the prolonged exposure to corticoids, reduce colectomy rates and its perioperative complications.

Mesotelioma benigno como causa de dolor abdominal inespecífico en un paciente con Enfermedad de Crohn / Benign multicystic peritoneal mesothelioma in a patient with Crohn disease

Benign multicystic peritoneal mesothelioma is an uncommon lesion arising from the peritoneal mesothelium. It is asymptomatic or presents with unspecific symptoms. Imaging techniques may reveal it, however the final diagnosis can only be made by histopathology. Surgery is the only effective treatment considering its high recurrence rate. We report a 19 years old male with Crohn’s disease. Due to persistent abdominal pain, an abdominal magnetic resonance imaging was performed, showing a complex cystic mass in the lower abdomen. The patient underwent surgery and the lesion was completely resected. The pathological study reported a benign multicystic peritoneal mesothelioma.

Consenso chileno de prevención, diagnóstico y tratamiento de la diarrea asociada a Clostridium difficile / Chilean consensus of prevention, diagnosis and treatment of Clostridium difficile-associated diarrhea

Background: Clostridium dijfficile-associated diarrhea (CDAD) has become very important due to the increase in its incidence, severity, recurrence and the associated economic burden. Having a national consensus guideline is essential to improve its management. Objective: To build a multidisciplinary and evidence-based consensus in prevention, diagnosis and treatment of CDAD. Methods: We convened a panel of experts in the field of infectious diseases, gastroenterology, evidence-based medicine and consensus methodology. The panel conducted a structured review of published literature in CDAD evaluating evidence levels and recommendation degree according to the methodology proposed by the GRADE working-group. A modified three-round Delphi technique was used to reach a consensus among the experts. Results: A group of 16 experts was established, 12 of them answered 18 clinically relevant questions. The levels of agreement achieved by the panel of 16 experts were 79% in the first round and 100% in the second and third round. The main consensus recommendations in prevention are: restricting the use of proton-pump inhibitors, primary prophylaxis with probiotics in antibiotics users, education of health personnel, isolation for patients hospitalized with CDAD, and cleaning the rooms exposed to C. difficile with products based in chlorine or hydrogen peroxide. In the diagnosis: use of biology molecular-based techniques is preferred and if not available, glutamate dehydrogenase-based algorithms may be recommended. With regard to treatment: the use of oral metronidazole in mild-moderate CDAD and oral vancomycin in severe CDAD are recommended. Treat the first recurrence with the same antibiotics according to severity. In the case of second and subsequent recurrences consider prolonged therapy with vancomycin, rifaximin or fecal microbiota transplant. Conclusion: The first Chilean consensus on prevention, diagnosis and treatment of CDAD is presented, which is a major step in improving national standards in the management of this disease.

Introducción: La diarrea asociada a Clostridium difficile (DACD) ha adquirido gran relevancia debido al aumento en su incidencia, gravedad, capacidad de recurrencia y carga económica asociada. Contar con una guía de consenso local es fundamental para mejorar su manejo. Objetivo: Elaborar un consenso multidisciplinara y basado en la evidencia en la prevención, diagnóstico y tratamiento de la DACD. Métodos: Se convocó a un panel de expertos en el área de enfermedades infecciosas, gastroenterología, medicina basada en la evidencia y metodología de consenso. El panel realizó una revisión estructurada de la literatura científica publicada en DACD evaluando el nivel de la evidencia y recomendación utilizando el sistema GRADE. Una técnica de Delfi modificada de tres rondas fue utilizada para alcanzar un consenso entre los expertos. Resultados: Se estableció un grupo de 16 expertos, 12 de ellos respondieron 18 preguntas de relevancia clínica. Los niveles de acuerdo alcanzados por el panel de 16 expertos fueron de 79% en la primera ronda y 100% en la segunda y tercera ronda. Las principales recomendaciones en prevención son: restricción del uso de inhibidores de la bomba de protones, profilaxis primaria con probióticos en usuarios de antimicrobianos de corto plazo, educación del personal de salud, aislamiento de contacto en pacientes hospitalizados con DACD y aseo de las habitaciones expuestas a C. difficile con productos en base a cloro o peróxido de hidrógeno. En el diagnóstico se recomienda: el uso de técnicas basadas en biología molecular y como alternativa algoritmos en base a glutamato deshidrogenasa. Con respecto al tratamiento, se recomienda el uso de metronidazol oral en DACD leve-moderada y vancomicina oral en DACD grave. El tratamiento de la primera recurrencia es con los mismos antimicrobianos de acuerdo a la gravedad, considerando en la segunda recurrencia y posteriores terapia prolongada con vancomicina, rifaximina o trasplante de microbiota fecal. Conclusión: Se presenta el primer consenso chileno en prevención, diagnóstico y tratamiento de DACD, paso trascendental en mejorar los estándares locales en el manejo de esta enfermedad.

Esporas de Clostridium difficile y su relevancia en la persistencia y transmisión de la infección / Clostridium difficile spores and its relevance in the persistence and transmission of the infection

C. difficile is an anaerobic spore former pathogen and the most important etiologic agent of nosocomial and community acquired antibiotics associated diarrheas. C. difficile infections (CDI) are responsible for an elevated rate of morbidity in developed and developing countries. Although the major virulence factors responsible for clinical symptoms of CDI are the two toxins TcdA and TcdB, C. difficile spores are the main vehicle of infection, persistence and transmission of CDI. Recent work has unrevealed unique properties of C. difficile spores that make them remarkable morphotypes of persistence and transmission in the host, including their resistance to antibiotics, the host immune response and disinfectants. The present review summarizes relevant aspects of C. difficile spore biology that have major implications from a clinical and medical perspective.

Clostridium difficile es un patógeno anaerobio, formador de esporas y el agente etiológico más importante de las diarreas asociadas a antimicrobianos, tanto nosocomiales como adquiridas en la comunidad. Las infecciones asociadas a C. difficile poseen una elevada tasa de morbilidad en países desarrollados y en vías de desarrollo. Los dos factores de virulencia principales son TcdA y TcdB, toxinas que causan la remodelación del citoesqueleto lo cual desencadena los síntomas clínicos asociados a esta enfermedad infecciosa. A pesar que las esporas de C. difficile son el principal vehículo de infección, persistencia en el hospedero y de transmisión, pocos estudios se han enfocado sobre este clave aspecto. Es altamente probable que la espora juegue roles esenciales en los episodios de recurrencia y de transmisión horizontal de la infección por este microorganismo. Estudios recientes han revelado características únicas de las esporas de C. difficile que las hacen capaces de ser altamente transmisibles y persistir dentro del hospedero. Más aún, algunas de estas propiedades están relacionadas con la resistencia de sus esporas a los desinfectantes más comúnmente usados en los recintos hospitalarios. La presente revisión resume los conocimientos más relevantes en la biología de las esporas de C. difficile, con un énfasis en aquellos aspectos con implicancias clínicas, incluido el control de infecciones en el ambiente hospitalario.

Genotipo y fenotipo de la enzima tiopurina metiltransferasa en población chilena / Phenotype and genotype of thiopurine methyltransferase in Chilean individuals

Background: Thiopurines (azathioprine and 6-mercaptopurine) are highly effective medications but with potential adverse effects. Thiopurine methyltransferase (TMPT) is the key enzyme in their pharmacokinetics and is genetically regulated. A low activity of TPMT is associated with myelotoxicity. The genotype and enzyme activity can vary by ethnicity. Aim: To study the activity and genotype of TPMT in a group of Chilean subjects. Material and Methods: In 200 healthy adult blood donors, TPMT activity was determined by high performance liquid chromatography (HPLC). Deficient, low, normal or high levels were defined when enzymatic activity was < 5, 6-24,25-55 and > 56 nmol/grHb/h, respectively. Genotyping of TPMT (*1, *2, *3A, *3B, *3C) was performed by PCR. Results: Seventy seven women (38.5%) and 123 men (61.5%), with an average age of 34.9 years were studied. Eighteen subjects (9%) had a low enzymatic activity, 178 (89%) had normal activity, 4 (2%) had high activity and no genotype deficient subjects were identified. The wild type genotype (*1) was found in 184 (92%) individuals and 16 (8%) were heterozygous for the variants: *2 (n = 2), *3A (n = 13) and *3C (n = 1). No homozygous subjects for these variants were identified. Wild type genotype had an increased enzymatic activity (40.8 ± 7.2 nmol/gHb/h) compared to heterozygous group (21.2 ± 3 nmol/ gHb/h; p < 0.001). Conclusions: Less than 10% of a Chilean population sample has a low enzymatic activity or allelic variants in the TPMT gene, supporting the use of thiopurines according to international recommendations.

Utilidad de la cápsula endoscópica como método diagnóstico en el estudio de patología de intestino delgado / Experience with capsule endoscopy diagnostic tool for the small intestine

Background: Wireless capsule endoscopy (CE) is a relatively new method to evaluate the small intestine. Aim: To evaluate the indications of CE in our center and assess whether specific indications are associated with best results during CE studies. Material and Methods: Retrospective analysis of 69 patients aged 9 to 85 years (36 males) subjected to a CE at our institution between April 2004 and October 2007. Results: The most common indications for CE were overt gastrointestinal bleeding in 43.5 percent of patients, iron deficiency anemia in 39.1 percent, suspicion of a small bowel tumor in 4.3 percent, chronic diarrhea in 4.3 percent and abdominalpain in 2.9 percent. CE was normal in 23.2 percent and was able to find lesions in 76.8 percent of the studies. Gastrointestinal bleeding, followed by iron deficiency anemia were the indications associated with the higher rates of positive findings during CE. Conclusions: Gastrointestinal bleeding and iron deficiency anemia were the indications that obtained the best diagnostic y ield for CE.