¿Ha disminuido la colectomía por crisis de colitis ulcerosa?

Background: Treatment for moderate-severe active ulcerative colitis (UC) includes steroids, biologic therapy and total colectomy. Aim: To describe the features of patients with moderate to severe active UC, their hospital evolution and need for colectomy. Material and Methods: Non-concurrent cohort study of all patients admitted to our institution with a diagnosis of moderate or severe UC crisis between January 2008 and May 2019. Truelove Witts (TW) criteria were used to categorize disease severity. Twelve-month colectomy-free survival was estimated with Kaplan-Meier survival analysis. Results: One hundred-twenty patients aged 16 to 89 (median 35) years had 160 admissions for acute moderate to severe UC. Median admission per patient was 1 (1-3), and median hospital stay was six days (1-49). Cytomegalovirus and Clostridioides difficile were found in 17.5 and 14.2% of crises, respectively. Corticosteroids were used in all crises and biologic therapy in 6.9% of them. Emergency or elective colectomies were performed in 18.3 and 6.7% of patients, respectively. The need for emergency total colectomy decreased from 24.6 to 7.8% (Risk ratio 3.16, p < 0.01) between de first and second half of the study period. Kaplan-Meier analysis for long term colectomy-free survival in both periods confirmed this decrease (p < 0.01). Conclusions: Medical treatment for moderate to severe UC crises had a 86.3% success and a small percentage required emergency total colectomy. Emergency surgery decreased in the last decade.

Ethnicity influences phenotype and clinical outcomes: Comparing a South American with a North American inflammatory bowel disease cohort.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn disease (CD), has emerged as a global disease with an increasing incidence in developing and newly industrialized regions such as South America. This global rise offers the opportunity to explore the differences and similarities in disease presentation and outcomes across different genetic backgrounds and geographic locations. Our study includes 265 IBD patients. We performed an exploratory analysis of the databases of Chilean and North American IBD patients to compare the clinical phenotypes between the cohorts. We employed an unsupervised machine-learning approach using principal component analysis, uniform manifold approximation, and projection, among others, for each disease. Finally, we predicted the cohort (North American vs Chilean) using a random forest. Several unsupervised machine learning methods have separated the 2 main groups, supporting the differences between North American and Chilean patients with each disease. The variables that explained the loadings of the clinical metadata on the principal components were related to the therapies and disease extension/location at diagnosis. Our random forest models were trained for cohort classification based on clinical characteristics, obtaining high accuracy (0.86 = UC; 0.79 = CD). Similarly, variables related to therapy and disease extension/location had a high Gini index. Similarly, univariate analysis showed a later CD age at diagnosis in Chilean IBD patients (37 vs 24; P = .005). Our study suggests a clinical difference between North American and Chilean IBD patients: later CD age at diagnosis with a predominantly less aggressive phenotype (39% vs 54% B1) and more limited disease, despite fewer biological therapies being used in Chile for both diseases.

Targeting Sphingosine-1-Phosphate Signaling in Immune-Mediated Diseases: Beyond Multiple Sclerosis.

Sphingosine-1-phosphate (S1P) is a bioactive lipid metabolite that exerts its actions by engaging 5 G-protein-coupled receptors (S1PR1-S1PR5). S1P receptors are involved in several cellular and physiological events, including lymphocyte/hematopoietic cell trafficking. An S1P gradient (low in tissues, high in blood), maintained by synthetic and degradative enzymes, regulates lymphocyte trafficking. Because lymphocytes live long (which is critical for adaptive immunity) and recirculate thousands of times, the S1P-S1PR pathway is involved in the pathogenesis of immune-mediated diseases. The S1PR1 modulators lead to receptor internalization, subsequent ubiquitination, and proteasome degradation, which renders lymphocytes incapable of following the S1P gradient and prevents their access to inflammation sites. These drugs might also block lymphocyte egress from lymph nodes by inhibiting transendothelial migration. Targeting S1PRs as a therapeutic strategy was first employed for multiple sclerosis (MS), and four S1P modulators (fingolimod, siponimod, ozanimod, and ponesimod) are currently approved for its treatment. New S1PR modulators are under clinical development for MS, and their uses are being evaluated to treat other immune-mediated diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis. A clinical trial in patients with COVID-19 treated with ozanimod is ongoing. Ozanimod and etrasimod have shown promising results in IBD; while in phase 2 clinical trials, ponesimod has shown improvement in 77% of the patients with psoriasis. Cenerimod and amiselimod have been tested in SLE patients. Fingolimod, etrasimod, and IMMH001 have shown efficacy in RA preclinical studies. Concerns relating to S1PR modulators are leukopenia, anemia, transaminase elevation, macular edema, teratogenicity, pulmonary disorders, infections, and cardiovascular events. Furthermore, S1PR modulators exhibit different pharmacokinetics; a well-established first-dose event associated with S1PR modulators can be mitigated by gradual up-titration. In conclusion, S1P modulators represent a novel and promising therapeutic strategy for immune-mediated diseases.

Mucosal Exposure to Cigarette Components Induces Intestinal Inflammation and Alters Antimicrobial Response in Mice.

The main environmental risk factor associated with the development of Crohn's disease (CD) is cigarette smoking. Although the mechanism is still unknown, some studies have shown that cigarette exposure affects the intestinal barrier of the small bowel. Among the factors that may be involved in this process are Paneth cells. These specialized epithelial cells are located into the small intestine, and they are able to secrete antimicrobial peptides, having an essential role in the control of the growth of microorganisms. Alterations in its function are associated with inflammatory processes, such as CD. To study how cigarette components impact ileum homeostasis and Paneth cells integrity, we used intragastric administration of cigarette smoke condensate (CSC) in mice. Our results showed that inflammation was triggered after mucosal exposure of CSC, which induced particular alterations in Paneth cells granules, antimicrobial peptide production, and a reduction of bactericidal capacity. In fact, exposure to CSC generated an imbalance in the fecal bacterial population and increased the susceptibility of mice to develop ileal damage in response to bacterial infection. Moreover, our results obtained in mice unable to produce interleukin 10 (IL-10-/- mice) suggest that CSC treatment can induce a symptomatic enterocolitis with a pathological inflammation in genetically susceptible individuals.

Experiencia de educación continua en línea en gastroenterología para médicos no especialistas / Experience of continuing online education in gastroenterology for non specialist medical doctors

Background: Continuing education is essential for health professions and online courses can be a good way for professional development. Aim: To describe the experience with online courses for continuing education in hepatology and gastroenterology and to analyze their educational impact. Material and Methods: A three years' experience in courses on liver diseases and digestive tract is described. Their curricular design, methodology, and the educational impact was analyzed using the four levels of the Kirkpatrick's model. Results: On average, there were 321 students per course (2015-2017). 94% were Chilean and 6% from abroad (20 countries). In the educational impact analysis, in level 1 "reaction": 93% said that the course fulfilled their expectations and 92% would recommend it. In level 2 "learning": 42% approved the courses. Level 3 "behavior" was not evaluated and level 4 "organizational change" highlighted that the traditional face-to-face continuing education model of Chilean Gastroenterology Society (SChG) changed to full distance model in these three courses, with 1284 students from South America, Asia and Europe, in a 3-years-period. Additionally, these programs were included in the Medical Society of Santiago (SMS) continuing education agenda. Conclusions: The alliance between the SMS and the SChG generated on line courses that meet the educational needs of physicians and medical students, with excellent results and student perception.

Heme Oxygenase-1 as a Modulator of Intestinal Inflammation Development and Progression.

Heme Oxygenase 1 (HMOX1) is an enzyme that catalyzes the reaction that degrades the heme group contained in several important proteins, such as hemoglobin, myoglobin, and cytochrome p450. The enzymatic reaction catalyzed by HMOX1 generates Fe2+, biliverdin and CO. It has been shown that HMOX1 activity and the by-product CO can downmodulate the damaging immune response in several models of intestinal inflammation as a result of pharmacological induction of HMOX1 expression and the administration of non-toxic amounts of CO. Inflammatory Bowel Diseases, which includes Crohn's Disease (CD) and Ulcerative Colitis (UC), are one of the most studied ailments associated to HMOX1 effects. However, microbiota imbalances and infections are also important factors influencing the occurrence of acute and chronic intestinal inflammation, where HMOX1 activity may play a major role. As part of this article we discuss the immune modulatory capacity of HMOX1 during IBD, as well during the infections and interactions with the microbiota that contribute to this inflammatory disease.

[Outcome of surgery for Crohn's colitis. Review of 28 cases]. / Colitis de Crohn: resultados del tratamiento quirúrgico y evolución alejada.

BACKGROUND: Exclusive involvement of the colon or rectum in Crohn's disease, called Crohn's colitis, (CC) occurs in about 25% of these patients. AIM: To analyze early surgical results and long-term outcomes of patients undergoing surgery for CC. MATERIAL AND METHODS: Review of a prospective database, identifying patients with Crohn's disease operated between 2003 and 2015 and excluding those with ileocecal disease. We analyzed demographic data, pre and postoperative pharmacological treatment, operations, morbidity and the need for a second bowel resection at follow-up. RESULTS: We reviewed data from 28 patients aged 17 to 72 years (15 men). Twenty-seven (96.4%) had previous pharmacological treatment, 11 received monoclonal antibodies. The most common indications for surgical treatment were failure of medical treatment in 15 cases, acute severe colitis in 12 and anemia/malnutrition in eight. Total colectomy was performed in 17 (61%) patients, proctocolectomy in 8 (29%) and segmental colectomies in 3 (11%). Sixteen (57%) were operated laparoscopically. Major postoperative complications were observed in 5 (18%). Four needed a reintervention. There was no operative mortality. During a 55 months median follow-up of 27 patients, seven (26%) required a second bowel resection, one of them for recurrence. Nineteen (70%) patients had an ostomy, which was permanent in 11. Fifteen patients are without medical treatment. CONCLUSIONS: Most of the reviewed patients required total colectomy for the control of the disease with a low surgical morbidity. Two-thirds required an ileostomy, which became permanent in half of them.

Impact of Cigarette Smoking on the Gastrointestinal Tract Inflammation: Opposing Effects in Crohn's Disease and Ulcerative Colitis.

Cigarette smoking is a major risk factor for gastrointestinal disorders, such as peptic ulcer, Crohn's disease (CD), and several cancers. The mechanisms proposed to explain the role of smoking in these disorders include mucosal damage, changes in gut irrigation, and impaired mucosal immune response. Paradoxically, cigarette smoking is a protective factor for the development and progression of ulcerative colitis (UC). UC and CD represent the two most important conditions of inflammatory bowel diseases, and share several clinical features. The opposite effects of smoking on these two conditions have been a topic of great interest in the last 30 years, and has not yet been clarified. In this review, we summarize the most important and well-understood effects of smoking in the gastrointestinal tract; and particularly, in intestinal inflammation, discussing available studies that have addressed the causes that would explain the opposite effects of smoking in CD and UC.

Colitis de Crohn: resultados del tratamiento quirúrgico y evolución alejada / Outcome of surgery for Crohn's colitis: review of 28 cases

Background: Exclusive involvement of the colon or rectum in Crohn's disease, called Crohn's colitis, (CC) occurs in about 25% of these patients. Aim: To analyze early surgical results and long-term outcomes of patients undergoing surgery for CC. Material and Methods: Review of a prospective database, identifying patients with Crohn's disease operated between 2003 and 2015 and excluding those with ileocecal disease. We analyzed demographic data, pre and postoperative pharmacological treatment, operations, morbidity and the need for a second bowel resection at follow-up. Results: We reviewed data from 28 patients aged 17 to 72 years (15 men). Twenty-seven (96.4%) had previous pharmacological treatment, 11 received monoclonal antibodies. The most common indications for surgical treatment were failure of medical treatment in 15 cases, acute severe colitis in 12 and anemia/malnutrition in eight. Total colectomy was performed in 17 (61%) patients, proctocolectomy in 8 (29%) and segmental colectomies in 3 (11%). Sixteen (57%) were operated laparoscopically. Major postoperative complications were observed in 5 (18%). Four needed a reintervention. There was no operative mortality. During a 55 months median follow-up of 27 patients, seven (26%) required a second bowel resection, one of them for recurrence. Nineteen (70%) patients had an ostomy, which was permanent in 11. Fifteen patients are without medical treatment. Conclusions: Most of the reviewed patients required total colectomy for the control of the disease with a low surgical morbidity. Two-thirds required an ileostomy, which became permanent in half of them.

[Practical clues for a fecal microbiota transplantation by colonoscopy for recurrent Clostridium difficile infection. Experience in a University center]. / Claves prácticas para un trasplante de microbiota fecal por colonoscopía en infección por Clostridium difficile recurrente. Experiencia en un centro universitario.

Fecal microbiota transplantation (FMT) is a highly effective therapy in recurrent Clostridium difficile. The best route to administrate the fecal matter has not been established yet. However, the lower gastrointestinal route by colonoscopy is effective and safe, presenting a higher acceptance by patients. In addition, this route allows an evaluation of colonic mucosa seeking for differential diagnostics. We present a case series of FMT performed in our institution by colonoscopy, highlighting outcomes and practical aspects for its implementation.

Claves prácticas para un trasplante de microbiota fecal por colonoscopía en infección por Clostridium difficile recurrente. Experiencia en un centro universitario / Practical clues for a fecal microbiota transplantation by colonoscopy for recurrent Clostridium difficile infection. Experience in a University center

Resumen El trasplante de microbiota fecal (TMF) constituye una terapia altamente eficaz en la infección por Clostridium difficile (ICD) recurrente. La mejor vía de administración del material fecal aún no ha sido establecida; sin embargo, la vía baja a través de colonoscopía resulta eficaz, segura y de mayor aceptación por los pacientes, permitiendo además el examen de la mucosa del colon en busca de diagnósticos diferenciales. Presentamos una serie de casos de TMF realizados en nuestra institución a través de colonoscopía, destacando los resultados y aspectos prácticos para su implementación.

Fecal microbiota transplantation (FMT) is a highly effective therapy in recurrent Clostridium difficile. The best route to administrate the fecal matter has not been established yet. However, the lower gastrointestinal route by colonoscopy is effective and safe, presenting a higher acceptance by patients. In addition, this route allows an evaluation of colonic mucosa seeking for differential diagnostics. We present a case series of FMT performed in our institution by colonoscopy, highlighting outcomes and practical aspects for its implementation.

Solar radiation is inversely associated with inflammatory bowel disease admissions.

OBJECTIVE: To explore the associations between latitude and solar radiation with inflammatory bowel disease admission rates in Chile, the country with the largest variation in solar radiation in the world. PATIENTS AND METHODS: This is an ecological study, which included data on all hospital-admitted population for inflammatory bowel disease between 2001 and 2012, according to different latitudes and solar radiation exposures in Chile. The data were acquired from the national hospital discharge database from the Department of Health Statistics and Information of the Chilean Ministry of Health. RESULTS: Between 2001 and 2012 there were 12,869 admissions due to inflammatory bowel disease (69% ulcerative colitis, 31% Crohn's disease). Median age was 36 years (IQR: 25-51); 57% were female. The national inflammatory bowel disease admission rate was 6.52 (95% CI: 6.40-6.63) per 100,000 inhabitants with increasing rates over the 12-year period. In terms of latitude, the highest admission rates for pediatric ulcerative colitis and Crohn's disease, as well as adult ulcerative colitis, were observed in the southernmost region with lowest annual solar radiation. Linear regression analysis showed that regional solar radiation was inversely associated with inflammatory bowel disease admissions in Chile (ß: -.44, p = .03). CONCLUSIONS: Regional solar radiation was inversely associated with inflammatory bowel disease admission rates in Chile; inflammatory bowel disease admissions were highest in the southernmost region with lowest solar radiation. Our results support the potential role of vitamin D deficiency on inflammatory bowel disease flares.

A Potential Role of Salmonella Infection in the Onset of Inflammatory Bowel Diseases.

Inflammatory bowel disease (IBD) includes a set of pathologies that result from a deregulated immune response that may affect any portion of the gastrointestinal tract. The most prevalent and defined forms of IBD are Crohn's disease and ulcerative colitis. Although the etiology of IBD is not well defined, it has been suggested that environmental and genetic factors contribute to disease development and that the interaction between these two factors can trigger the pathology. Diet, medication use, vitamin D status, smoking, and bacterial infections have been proposed to influence or contribute to the onset or development of the disease in susceptible individuals. The infection with pathogenic bacteria is a key factor that can influence the development and severity of this disease. Here, we present a comprehensive review of studies performed in human and mice susceptible to IBD, which supports the notion that infection with bacterial pathogens, such as Salmonella, could promote the onset of IBD due to permanent changes in the intestinal microbiota, disruption of the epithelial barrier and alterations of the intestinal immune response after infection.

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.

Impacto del cigarrillo en el tracto gastrointestinal: efecto diferencial en enfermedad de Crohn y colitis ulcerosa / Impact of the cigarette on the gastrointestinal tract: differential effect in Crohn's disease and ulcerative colitis

El impacto del consumo de cigarrillo a nivel respiratorio y cardiovascular ha sido extensamente investigado, sin embargo, aún queda mucho por estudiar sobre su impacto en el tracto gastrointestinal. Está demostrado que el tabaquismo es un importante factor de riesgo para desórdenes gastrointestinales, incluyendo úlceras pépticas, Enfermedad de Crohn y distintos tipos de cáncer. Los mecanismos propuestos incluyen daños a nivel de la mucosa, alteraciones en la irrigación del tejido y cambios en la respuesta inmune. Paradojalmente, el consumo de cigarrillo constituye un factor protector para el desarrollo y la progresión de la Colitis Ulcerosa. Esta patología, junto a la Enfermedad de Crohn, conforman las dos entidades más importantes dentro de las Enfermedades Inflamatorias Intestinales y comparten diversas características. El impacto diferencial del consumo de cigarrillo entre ambas ha sido un tema de gran interés en los últimos treinta años, y aún no ha logrado ser esclarecido. En esta revisión describiremos los efectos conocidos del tabaquismo sobre el tracto gastrointestinal, y particularmente que intentan explicar el efecto opuesto del cigarrillo en la Enfermedad de Crohn y la Colitis Ulcerosa.(AU)

The impact of cigarette smoking on respiratory and cardiovascular diseases has been extensively researched, although further investigation is required to elucidate its impact on the gastrointestinal tract. It has been demonstrated that smoking is a major risk factor for gastrointestinal disorders, including peptic ulcers, Crohn's disease and various cancers. Proposed mechanisms include mucosal damage, changes in gut irrigation and changes in the mucosal immune response. Paradoxically, cigarette smoking is a protective factor for the development and progression of Ulcerative Colitis. Both Ulcerative colitis and Crohn's disease represent the two most important entities in Inflammatory Bowel Diseases and share several characteristics. The differential impact of smoking between these two disorders has been a topic of great interest in the last thirty years, and has yet to be clarified. In this review we describe the known effects of smoking on the gastrointestinal tract, and particularly in the intestinal inflammation, delving into the available studies that attempt to explain the opposite effect of smoking in Crohn's disease and Ulcerative colitis.(AU)

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.

Controversias en el manejo de la de colitis ulcerosa grave en Chile / Controversies in the management of severe ulcerative colitis in Chile

Ulcerative colitis is a chronic inflammation in the mucosa layer of the colon characterized by activity and remitting episodes of varying severity and extension. Most of the flares are mild to moderate. They require outpatient treatment and have a good prognosis. The severe crises can have a high mortality if not treated on time. The success of the therapy depends on a multidisciplinary team.

La colitis ulcerosa en una inflamación crónica de la mucosa del intestino grueso que se caracteriza por episodios de actividad y remisiones de gravedad y extensión variable. La mayoría de las crisis son leves a moderadas, requieren tratamiento ambulatorio y son de buen pronóstico. Las crisis graves pueden llegar a tener una alta mortalidad si no son tratadas a tiempo. El éxito de la terapia depende de un equipo multidisciplinario.

Interleukin-10 plays a key role in the modulation of neutrophils recruitment and lung inflammation during infection by Streptococcus pneumoniae.

Streptococcus pneumoniae is a major aetiological agent of pneumonia worldwide, as well as otitis media, sinusitis, meningitis and sepsis. Recent reports have suggested that inflammation of lungs due to S. pneumoniae infection promotes bacterial dissemination and severe disease. However, the contribution of anti-inflammatory molecules to the pathogenesis of S. pneumoniae remains unknown. To elucidate whether the production of the anti-inflammatory cytokine interleukin-10 (IL-10) is beneficial or detrimental for the host during pneumococcal pneumonia, we performed S. pneumoniae infections in mice lacking IL-10 (IL-10(-/-) mice). The IL-10(-/-) mice showed increased mortality, higher expression of pro-inflammatory cytokines, and an exacerbated recruitment of neutrophils into the lungs after S. pneumoniae infection. However, IL-10(-/-) mice showed significantly lower bacterial loads in lungs, spleen, brain and blood, when compared with mice that produced this cytokine. Our results support the notion that production of IL-10 during S. pneumoniae infection modulates the expression of pro-inflammatory cytokines and the infiltration of neutrophils into the lungs. This feature of IL-10 is important to avoid excessive inflammation of tissues and to improve host survival, even though bacterial dissemination is less efficient in the absence of this cytokine.

Achieving the best bowel preparation for colonoscopy.

Bowel preparation is a core issue in colonoscopy, as it is closely related to the quality of the procedure. Patients often find that bowel preparation is the most unpleasant part of the examination. It is widely accepted that the quality of cleansing must be excellent to facilitate detecting neoplastic lesions. In spite of its importance and potential implications, until recently, bowel preparation has not been the subject of much study. The most commonly used agents are high-volume polyethylene glycol (PEG) electrolyte solution and sodium phosphate. There has been some confusion, even in published meta-analyses, regarding which of the two agents provides better cleansing. It is clear now that both PEG and sodium phosphate are effective when administered with proper timing. Consequently, the timing of administration is recognized as one of the central factors to the quality of cleansing. The bowel preparation agent should be administered, at least in part, a few hours in advance of the colonoscopy. Several low volume agents are available, and either new or modified schedules with PEG that usually improve tolerance. Certain adjuvants can also be used to reduce the volume of PEG, or to improve the efficacy of other agents. Other factors apart from the choice of agent can improve the quality of bowel cleansing. For instance, the effect of diet before colonoscopy has not been completely clarified, but an exclusively liquid diet is probably not required, and a low-fiber diet may be preferable because it improves patient satisfaction and the quality of the procedure. Some patients, such as diabetics and persons with heart or kidney disease, require modified procedures and certain precautions. Bowel preparation for pediatric patients is also reviewed here. In such cases, PEG remains the most commonly used agent. As detecting neoplasia is not the main objective with these patients, less intensive preparation may suffice. Special considerations must be made for patients with inflammatory bowel disease, including safety and diagnostic issues, so that the most adequate agent is chosen. Identifying neoplasia is one of the main objectives of colonoscopy with these patients, and the target lesions are often almost invisible with white light endoscopy. Therefore excellent quality preparation is required to find these lesions and to apply advanced methods such as chromoendoscopy. Bowel preparation for patients with lower gastrointestinal bleeding represents a challenge, and the strategies available are also reviewed here.

Rendimiento de índices pronósticos en infección asociada a Clostridium difficile grave: Análisis retrospectivo en un hospital universitario / Performance of prognostic index in severe Clostridium difficile-associated infection: Retrospective analysis in a university hospital

Introduction: By consensus severe, Clostridium difficile-associated infection (CDAI) is one that results in hospitalization in ICU, colectomy or death within 30 days. Multiple prognostic indices (IP) attempt to predict these adverse events. Objective: To evaluate the performance of 4 PI in predicting severe CDI. Methods: Hospitalized patients ≥ 18 years old with ICD were retrospectively evaluated. Patients with recurrent infection or hematological cancer were excluded. Four PI were evaluated: UPMC version 1, Calgary version 1, Hines VA and Calgary version 2. Results: Seven of 81 patients (8.1%) met the definition of severe CDI. Positive predicted value (PPV) and negative predicted value (NPV) of PI ranged from 20-75% and 91.3-95.7%, respectively. Only Hines VA index had a satisfactory Kappa index (0.74; 95% CI 0.41-1) with a PPV of 75% and NPV of 95,7%. However, because of the variables included, this PI could be calculated only in 32.6% of patients. Conclusion: Hines VA index has the best predicted value and agreement to rule out a severe CDI. Like others PI it has the limitation of including difficult variables to assess in all patients and tends to overestimate an unfavorable course.

Introducción: Por consenso, la infección asociada a Clostridium difficile (IACD) grave es aquella que resulta en hospitalización en unidad de cuidados intensivos, colectomía o muerte dentro de 30 días. Múltiples índices pronósticos (IP) intentan predecir estos eventos adversos. Objetivo: evaluar el rendimiento de cuatro IP en la predicción de IACD grave. Metodología: pacientes hospitalizados ≥ 18 años con IACD fueron evaluados retrospectivamente. Se excluyeron pacientes con infección recurrente o cáncer hematológico. Se evaluaron cuatro IP: UPMC versión 1, Calgary versión 1, Hines VA y Calgary versión 2. Resultados: Siete de 81 pacientes (8,1%) presentaron una IACD grave. El valor predictor positivo (VPP) y valor predictor negativo (VPN) de los IP varió entre 20-75% y 91,3-95,7%, respectivamente. Sólo el índice de Hines VA tuvo un índice Kappa satisfactorio (0,74;IC 95% 0,46-1) con un VPP de 75% y un VPN de 95,7%. Sin embargo, por las variables incluidas en este IP, sólo pudo ser calculado en 32,6% de los pacientes. Conclusión: El índice de Hines VA presenta el mejor valor predictor y concordancia para descartar una IACD grave. Como otros IP, tiene la limitación de incluir variables difícilmente evaluables en todos los pacientes y tiende a sobreestimar un curso desfavorable.