After surgically induced remission, ileal and colonic mucosa-associated microbiota predicts Crohn's disease recurrence.

BACKGROUND AND AIMS: Investigating the tissue-associated microbiota after surgically induced remission may help to understand the mechanisms initiating intestinal inflammation in Crohn's disease. METHODS: Crohn's disease patients undergoing ileocolic resection were prospectively recruited in six academic centers. Biopsy samples from the neoterminal ileum, colon and rectosigmoid were obtained from colonoscopies performed after surgery. Microbial DNA was extracted for 16S rRNA gene sequencing. Microbial diversity and taxonomic differential relative abundance were analyzed. A random forest model was applied to analyze the performance of clinical and microbial features to predict recurrence. A Rutgeerts score ≥i2 was deemed as endoscopic recurrence. RESULTS: A total of 349 postoperative colonoscopies and 944 biopsy samples from 262 Crohn's disease patients were analyzed. Ileal inflammation accounted for most of the explained variance of the ileal and colonic mucosa-associated microbiota. Samples obtained from 97 patients who were in surgically induced remission at first postoperative colonoscopy who went on to develop endoscopic recurrence at second colonoscopy showed lower diversity and microbial deviations when compared to patients who remained in endoscopic remission. Depletion of genus Anaerostipes and increase of several genera from class Gammaproteobacteria at the three biopsy sites increase the risk of further recurrence. Gut microbiome was able to predict future recurrence better than clinical features. CONCLUSION: Ileal and colonic mucosa-associated microbiome deviations precede development of new onset ileal inflammation after surgically induced remission and show good predictive performance for future recurrence. These findings suggest that targeted microbial modulation is a plausible modality to prevent postoperative Crohn's disease recurrence.

Altered Gut Microbiome Composition and Function Are Associated With Gut Barrier Dysfunction in Healthy Relatives of Patients With Crohn's Disease.

BACKGROUND & AIMS: The gut microbiome has been suggested to play a role in gut barrier hemostasis, but data are scarce and limited to animal studies. We therefore aimed to assess whether alterations in gut microbial composition and functional pathways are associated with gut barrier function in a cohort of healthy first-degree relatives of patients with Crohn's disease. METHODS: We used the Crohn's and Colitis Canada Genetic Environmental Microbial (CCC-GEM) cohort of healthy first-degree relatives of patients with Crohn's disease. Gut barrier function was assessed using the urinary fractional excretion of lactulose-to-mannitol ratio (LMR). Microbiome composition was assessed by sequencing fecal 16S ribosomal RNA. The cohort was divided into a discovery cohort (n = 2472) and a validation cohort (n = 655). A regression model was used to assess microbial associations with the LMR. A random forest classifier algorithm was performed to assess microbial community contribution to barrier function. RESULTS: Individuals with impaired barrier function (LMR >0.025) had reduced alpha-diversity (Chao1 index, P = 4.0e-4) and altered beta-diversity (Bray-Curtis dissimilarity index, R2 = 0.001, P = 1.0e-3) compared with individuals with an LMR ≤0.025. When taxa were assessed individually, we identified 8 genera and 52 microbial pathways associated with an LMR >0.025 (q < 0.05). Four genera (decreased prevalence of Adlercreutzia, Clostridia UCG 014, and Clostridium sensu stricto 1 and increased abundance of Colidextribacter) and 8 pathways (including decreased biosynthesis of glutamate, tryptophan, and threonine) were replicated in the validation cohort. The random forest approach revealed that the bacterial community is associated with gut barrier function (area under the curve, 0.63; P = 1.4e-6). CONCLUSIONS: The gut microbiome community and pathways are associated with changes in gut barrier function. These findings may identify potential microbial targets to modulate gut barrier.

Genotype Prevalence of Lactose Deficiency, Vitamin D Deficiency, and the Vitamin D Receptor in a Chilean Inflammatory Bowel Disease Cohort: Insights from an Observational Study.

Lactose intolerance (LI) and vitamin D deficiency (VDD) have been linked to inflammatory bowel disease (IBD). We conducted an observational study in 192 Chilean IBD patients to investigate the prevalence of a specific gene variant (LCT-13910 CC genotype) associated with LI and the prevalence of VDD/Vitamin D Receptor (VDR) gene variants. Blood samples were analyzed using Illumina's Infinium Global Screening Array. The LCT-13910 CC genotype was found in 61% of IBD patients, similar to Chilean Hispanic controls and lower than Chilean Amerindian controls. The frequency of the LCT-13910-C allele in Chilean IBD patients (0.79) was comparable to the general population and higher than Europeans (0.49). Regarding VDR and VDD variants, in our study, the rs12785878-GG variant was associated with an increased risk of IBD (OR = 2.64, CI = 1.61-4.32; p-value = 0.001). Sixty-one percent of the Chilean IBD cohort have a genetic predisposition to lactose malabsorption, and a significant proportion exhibit genetic variants associated with VDD/VDR. Screening for LI and VDD is crucial in this Latin American IBD population.

Association of leisure time and occupational physical activity with obesity and cardiovascular risk factors in Chile.

The aim of this study was to investigate the association between physical activity (PA), both occupational (OPA) and during leisure time (LTPA), with obesity and cardiovascular risk factors in Chilean adults. 5,157 participants from the Chilean National Health Survey 2009-2010 were included in this study. OPA and LTPA levels were assessed using the Global Physical Activity Questionnaire. The association between both PA with obesity and cardiovascular risk factors was determined using logistic regression. Our findings showed a significant trend between higher LTPA and lower odds for obesity (OR 0.64 [95% CI: 0.53; 0.76], central obesity 0.52 [0.44; 0.61]) and other cardiovascular risk factors including diabetes (OR: 0.72 [0.55; 0.94]), hypertension (OR: 0.59 [0.50; 0.71]) and metabolic syndrome (OR: 0.62 [0.50; 0.78]). In contrast, OPA was only associated with lower odds of diabetes (OR: 0.79 [0.65; 0.98]) and hypertension (0.85 [0.74; 0.98]). In conclusion, LTPA was associated with a lower risk of all major cardiovascular risk factors, whereas OPA was only associated with a lower risk of diabetes and hypertension.

[Association between adiposity and asthma]. / ¿Existe asociación entre asma y adiposidad en la población adulta chilena?

BACKGROUND: In people with asthma, adiposity is associated with more symptoms and less control of the disease whereas on those without asthma adiposity is associated with a higher risk of developing the disease. AIM: To investigate the association between asthma and adiposity markers in Chilean adults. MATERIAL AND METHODS: Data from 5,499 adults older than 15-years-old from the Chilean National Health Survey 20162017 were analyzed. Quintiles of body-mass index (BMI) and waist circumference (WC) were used as a proxy of adiposity. The association between asthma and quintiles of BMI and WC was determined by logistic regression. RESULTS: A higher BMI and WC was associated with a higher odds for asthma. This trend remained significant even after adjusting the models for socio-demographic factors, physical activity and smoking (Odds Ratio [OR] BMI: 1.13 [95% confidence intervals (CI): 1.04; 1.22], p < 0.01 and OR WC: 1.15 [95% IC: 1.06; 1.25], p < 0.01). CONCLUSIONS: A higher BMI and WC were positively associated with asthma.

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

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.

Hand grip strength and maximum peak expiratory flow: determinants of bone mineral density of adolescent students.

BACKGROUND: Maintaining and building healthy bones during the lifetime requires a complicated interaction between a number of physiological and lifestyle factors. Our goal of this study was to analyze the association between hand grip strength and the maximum peak expiratory flow with bone mineral density and content in adolescent students. METHODS: The research team studied 1427 adolescent students of both sexes (750 males and 677 females) between the ages of 11.0 and 18.9 years in the Maule Region of Talca (Chile). Weight, standing height, sitting height, hand grip strength (HGS), and maximum peak expiratory flow (PEF) were measured. Furthermore, bone mineral density (BMD) and total body bone mineral content (BMC) were determined by using the Dual-Energy X-Ray Absorptiometry (DXA). Hand grip strength and PEF were categorized in tertiles (lowest, middle, and highest). Linear regression was performed in steps to analyze the relationship between the variables. Differences between categories were determined through ANOVA. RESULTS: In males, the hand grip strength explained 18-19% of the BMD and 20-23% of the BMC. For the females, the percentage of variation occurred between 12 and 13% of the BMD and 17-18% of the BMC. The variation of PEF for the males was observed as 33% of the BMD and 36% of the BMC. For the females, both the BMD and BMC showed a variation of 19%. The HGS and PEF were divided into three categories (lowest, middle, and highest). In both cases, significant differences occurred in bone density health between the three categories. CONCLUSIONS: In conclusion, the HGS and the PEF related positively to the bone density health of both sexes of adolescent students. The adolescents with poor values for hand grip strength and expiratory flow showed reduced values of BMD and BMC for the total body. Furthermore, the PEF had a greater influence on bone density health with respect to the HGS of the adolescents of both sexes.

Secular trends of physical growth and abdominal adiposity of school children and adolescents living at a moderate altitude in Peru.

OBJECTIVE: Identify changes in physical growth and abdominal adiposity at an interval of 14 years in children and adolescents living at a moderate altitude in Peru. MATERIALS AND METHODS: The data comes from two cross-sectional studies carried out in the city of Arequipa, Peru, located at a moderate altitude of 2,320 meters. In 2001, 473 males and 482 females were assessed, and in 2015, 432 males and 403 females between 6.0 and 12.9 years old were evaluated. Data were collected in public state schools and measured using the anthropometric variables for weight, height, and waist circumference. Body mass index (BMI) was calculated according to age and sex. RESULTS: Positive trends for weight were identified for both males and females at all ages (p < .001). For height, significant increases were observed in males for all ages. No significant increases (p > .05) occurred in height for females between the ages of 6 and 8 years. However, commencing at age 9 until 12 years, females showed positive and significant increases (p < .001) in height. In 2015, BMI and waist circumference increased significantly for both sexes at all ages. DISCUSSION: Between 2001 and 2015, positive trends in physical growth and abdominal adiposity were identified for children and adolescents living in Arequipa, Peru. These changes may be associated with the rapid economic development in the country.

Validation of the Simplified Criteria for the Diagnosis of Autoimmune Hepatitis in Chilean-Hispanic Patients.

INTRODUCTION AND AIM: In 2008 the International autoimmune hepatitis (AIH) Group proposed the simplified diagnostic criteria for this disease. The original cohort study was performed in 11 international centers, but validation studies are scarce in Latin-America. The aim of this study is validate these criteria in Hispanic patients. MATERIAL AND METHODS: A retrospective cohort of patients undergoing percutaneous liver biopsy and follow-up of at least 12 months was recruited from a Chilean University hospital. Patients with previous immunosuppressive therapy and liver transplant recipients were excluded. The diagnostic accuracy was analyzed using as gold standard the clinical course during long-term follow-up. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) and area under the ROC curve (AUROC) were calculated. RESULTS: Four hundred eighty one patients were evaluated, 294 were included. 218 (74.15%) were female, mean age 48.5 (± 12.3) years, mean follow-up 34 (± 18) months. 66 patients had AIH or overlap syndrome (22.45%), 96 (32.65%) non-alcoholic steatohepatitis, 40 (13.61%) primary biliary cholangitis, 31 (10.54%) hepatitis C, 8 (2.72%) hepatitis B, 53 (18.02%) other etiologies. The AUROC for AIH simplified criteria was 0.976. Using a cutoff ≥ 6 and ≥ 7 points, the sensitivity was 86.4% and 54.6%; specificity, 98.7% and 99.6%; PPV, 95% and 97.3%; and NPV, 96.2% and 88.6%, respectively. CONCLUSION: Simplified criteria for the diagnosis of AIH have a high accuracy in our Chilean-Hispanic cohort. The female gender is strongly associated to AIH and could help in difficult cases. Further studies with a prospective design are necessary to confirm these observations.

Serum cytokeratin-18 fragment levels as noninvasive marker of nonalcoholic steatohepatitis in the chilean population. / Fragmento sérico de citoqueratina-18 como marcador no invasivo de esteatohepatitis no alcohólica en población chilena.

Nonalcoholic steatohepatitis (NASH) is the most aggressive form of nonalcoholic fatty liver disease (NAFLD) and involves the risk of progression to more advanced stages of liver disease. Non-invasive methods are needed to identify patients with NASH. OBJECTIVE: To evaluate the diagnostic performance of the determination of serum levels of cytokeratin-18 (CK-18) as a non-invasive marker of NASH in the Chilean population. METHODS: Serum CK-18 levels were determined in a group of 41 patients with biopsy-proven NAFLD. NASH diagnosis was based on Brunt's criteria (histological parameters and ballooning), and the NAFLD activity score (NAS) and the presence of fibrosis were determined. The correlation between the NAFLD activity score (NAS) and CK-18 was evaluated with Spearman's rank correlation coefficient. A ROC curve was produced to assess the diagnostic value of CK-18 for NASH. The NAFLD fibrosis score (NFS) (to predict fibrosis and NASH) was compared to CK-18 with simple linear regression. Data were expressed in median [25th-75th percentile] and evaluated with the Wilcoxon rank test. RESULTS: The mean age of the study group (23% male) was 50.4±11.1 years. 34.2% were diagnosed with NASH (NAS≥5). CK-18 levels were significantly higher in patients with NASH versus those without NASH (183.6 IU/l [97.4 to 734.4] vs. 117.2 IU/l [83.8 to 954.8], p= 0.016). CK-18 levels were a good predictor of NASH on biopsy with an area under the curve (AUC) of 0.732 (95% CI, 0.572 to 0.897). A CK-18 cut-off of 130.5 IU/l had a sensitivity of 92.9%, specificity of 63%, positive predictive value of 56.5% and negative predictive value of 94.4%, and was able to correctly classify 73.2% of patients with NASH. NFS identified advanced liver fibrosis (AUC 0.739, 95% CI, 0.56-0.91), but was of limited value to identify NASH (AUC 0.413, 95% CI, 0.21-0.61). CONCLUSION: CK-18 is a good non-invasive marker for NASH. Although NFS was found to be an accurate marker of advanced liver fibrosis, it was not of value to identify NASH. In patients with NAFLD, CK-18 and NFS could be useful in predicting NASH and liver fibrosis, respectively.

[Management of severe ulcerative colitis: An up-to-date]. / Diagnóstico y manejo de colitis ulcerosa grave: Una mirada actualizada.

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.

[Physical activity patterns of school adolescents: Validity, reliability and percentiles proposal for their evaluation]. / Patrones de actividad física de adolescentes escolares: validez, confiabilidad y propuesta de percentiles para su evaluación.

Regular physical activity (PA) during childhood and adolescence is important for the prevention of non-communicable diseases and their risk factors. OBJECTIVES: To validate a questionnaire for measuring patterns of PA, verify the reliability, comparing the levels of PA aligned with chronological and biological age, and to develop percentile curves to assess PA levels depending on biological maturation. SUBJECTS AND METHOD: Descriptive cross-sectional study was performed on a sample non-probabilistic quota of 3,176 Chilean adolescents (1685 males and 1491 females), with a mean age range from 10.0 to 18.9 years. An analysis was performed on, weight, standing and sitting height. The biological age through the years of peak growth rate and chronological age in years was determined. Body Mass Index was calculated and a survey of PA was applied. The LMS method was used to develop percentiles. RESULTS: The values for the confirmatory analysis showed saturations between 0.517 and 0.653. The value of adequacy of Kaiser-Meyer-Olkin (KMO) was 0.879 and with 70.8% of the variance explained. The Cronbach alpha values ranged from 0.81 to 0.86. There were differences between the genders when aligned chronological age. There were no differences when aligned by biological age. Percentiles are proposed to classify the PA of adolescents of both genders according to biological age and sex. CONCLUSION: The questionnaire used was valid and reliable, plus the PA should be evaluated by biological age. These findings led to the development of percentiles to assess PA according to biological age and gender.

Outcome of relapsing Clostridium difficile infections do not correlate with virulence-, spore- and vegetative cell-associated phenotypes.

One of the main clinical challenges of Clostridium difficile infections (CDI) is the high rate of relapse episodes. The main determinants involved in relapse of CDI include the presence of antibiotic-resistant C. difficile spores in the colonic environment and a permanent state of dysbiosis of the microbiota caused by antibiotic therapy. A possible scenario is that phenotypes related to the persistence of C. difficile spores might contribute to relapsing infections. In this study, 8 C. difficile isolates recovered from 4 cases with relapsing infection, and 9 isolates recovered from single infection cases were analyzed for PCR ribotyping and the presence of tcdA, tcdB and cdtAB genes. Factors associated to spore persistence, sporulation, spore adherence and biofilm formation and sporulation during biofilm formation were characterized. We also evaluated motility and cytotoxicity. However, we observed no significant difference in the analyzed phenotypes among the different clinical outcomes, most likely due to the high variability observed among strains within clinical backgrounds in each phenotype and the small sample size. It is noteworthy that C. difficile spores adhered to similar extents to undifferentiated and differentiated Caco-2 cells. By contrast, spores of all clinical isolates tested had increased germination efficiency in presence of taurocholate, while decreased sporulation rate during biofilm development in the presence of glucose. In conclusion, these results show that, at least in this cohort of patients, the described phenotypes are not detrimental in the clinical outcome of the disease.

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

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.

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

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.

Inflammatory bowel disease associated with primary sclerosing cholangitis is associated with an altered gut microbiome and bile acid profile.

BACKGROUND: Primary sclerosing cholangitis associated with inflammatory bowel disease (IBD-PSC) carries significant morbidity compared to IBD without PSC. Alterations in microbial composition and bile acid (BA) profiles have been shown to modulate chronic inflammation in IBD, but data in IBD-PSC is scarce. We aimed to assess the differences in gut microbiome composition as well as in the BA profile and BA-related microbial functions between IBD-PSC and IBD-only. METHODS: 54 IBD-PSC and 62 IBD-only subjects were enrolled from 2012 to 2021. Baseline samples were collected for fecal DNA shotgun metagenomic sequencing, fecal and serum BA quantitation using mass spectrometry and fecal calprotectin. Liver fibrosis measured by transient elastography (TE) was assessed in the IBD-PSC group. Data was analyzed using general linear regression models and Spearman rank correlation tests. RESULTS: Patients with IBD-PSC had reduced microbial gene richness (p=0.004) and significant compositional shifts (PERMANOVA: R2=0.01, p=0.03) compared to IBD-only. IBD-PSC was associated with altered microbial composition and function, including decreased abundance of Blautia obeum, increased abundance of Veillonella atypica, Veillonella dispar and Clostridium scindens (q<0.05 for all), and increased abundance of microbial genes involved in secondary BA metabolism. Decreased serum sulfated and increased serum conjugated secondary BA were associated with IBD-PSC and increased liver fibrosis. CONCLUSION: We identified differences in microbial species, functional capacity and serum BA profiles in IBD-PSC compared with IBD-only. Our findings provide insight into the pathophysiology of IBD associated with PSC and suggest possible targets for modulating the risk and course of IBD in subjects with PSC.

Validation study of systems for noninvasive diagnosis of fibrosis in nonalcoholic fatty liver disease in Latin population.

Background. The incidence of liver cirrhosis is significantly high in Latin population. The high prevalence of nonalcoholic fatty liver disease NAFLD is likely partially responsible for these figures. Liver biopsy is not a practical diagnostic option in this scenario. The validation of noninvasive markers of fibrosis is important in populations with a high prevalence of NAFLD. Aim. To compare the diagnostic value of noninvasive assessment systems to detect fibrosis in a cohort of Latin patients with biopsy-proven NAFLD. Material and methods. Patients with biopsy-proven NAFLD were included. Noninvasive evaluations included calculations of NAFLD fibrosis, FIB-4, BARD scores, APRI, and AST/ALT ratio. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver-operating characteristic curve (AUROC) were calculated. Results. A total of 228 patients (mean age, 48.6 ± 12.7 years) were included. Fifty-one percent were women; 48% were overweight and 23% were obese. The severity of fibrosis was classified as G0, 56.6%; G1, 25%; G2, 6.6%; G3, 7%; and G4, 4.8%. The AUROC values for advanced fibrosis were 0.72 for the NAFLD fibrosis score, 0.74 for FIB-4 score, 0.67 for AST/ALT ratio, 0.66 for APRI score, and 0.65 for BARD score. In 54% of patients with undetermined FIB-4 score and in 60% of patients with undetermined NAFLD fibrosis score, fibrosis was observed in the liver biopsy. Conclusions. The NAFLD fibrosis, FIB-4, and APRI scores can be used for the noninvasive diagnosis of fibrosis. However, 25% of patients evaluated by these methods have an indeterminate degree of fibrosis.

Amerindian ancestry proportion as a risk factor for inflammatory bowel diseases: results from a Latin American Andean cohort.

Background and aims: Latin American populations remain underrepresented in genetic studies of inflammatory bowel diseases (IBDs). Most genetic association studies of IBD rely on Caucasian, African, and Asian individuals. These associations have yet to be evaluated in detail in the Andean region of South America. We explored the contribution of IBD-reported genetic risk variants to a Chilean cohort and the ancestry contribution to IBD in this cohort. Methods: A total of 192 Chilean IBD patients were genotyped using Illumina's Global Screening Array. Genotype data were combined with similar information from 3,147 Chilean controls. The proportions of Aymara, African, European, and Mapuche ancestries were estimated using the software ADMIXTURE. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for gender, age, and ancestry proportions. We also explored associations with previously reported IBD-risk variants independently and in conjunction with genetic ancestry. Results: The first and third quartiles of the proportion of Mapuche ancestry in IBD patients were 24.7 and 34.2%, respectively, and the corresponding OR was 2.30 (95%CI 1.52-3.48) for the lowest vs. the highest group. Only one variant (rs7210086) of the 180 reported IBD-risk SNPs was associated with IBD risk in the Chilean cohort (adjusted P = 0.01). This variant is related to myeloid cells. Conclusion: The type and proportion of Native American ancestry in Chileans seem to be associated with IBD risk. Variants associated with IBD risk in this Andean region were related to myeloid cells and the innate immune response.

[Clostridium difficile associated infections: an updated view]. / Infecciones causadas por Clostridium difficile: una visión actualizada.

Clostridium difficile is an emerging anaerobic, spore forming pathogen, recognized as the etiological agent of ~ 30% of antibiotic associated diarrheas. Clinical symptoms can fluctuate from mild to moderate diarrhea, pseudomembranous colitis and toxic megacolon. The incidence of C. difficile associated infections (CDAI) is ~ 1% of total hospitalized patients. CDAI has a mortality rate of ~1 to 5%, and a relapse rate of ~ 20%. The appearance of severe outbreaks of CDAI could be attributed to changes in the production of the two major virulence factors, the enterotoxins TcdA and TcdB, which produce massive epithelial damage. C. difficile spores play an essential role in transmission, initiation and persistence of CDAI. Recent advances in detection methods, development of novel therapies and prevention methods could allow a reduction on the frequency of CDAI. The objective of this review is to provide an updated view on the mechanisms of pathogenesis, epidemiology, risk factors, detection methods, treatment and prevention of CDAI.

Combined Histo-endoscopic Remission but not Endoscopic Healing Alone in Ulcerative Colitis is Associated with a Mucosal Transcriptional Profile Resembling Healthy Mucosa.

BACKGROUND AND AIMS: A composite endpoint of histological and endoscopic remission is proposed to be the most complete measure of mucosal healing in ulcerative colitis [UC]. We aim to establish the prognosis, and transcriptional and microbial features of histo-endoscopic remission and activity. METHODS: A cross-sectional endoscopic rectosigmoid colon sample collection from UC patients and healthy controls [HC] was performed for histopathology and host genome-wide RNA-sequencing. Histo-endoscopic remission and histo-endoscopic activity were defined as Mayo endoscopic subscore [MES] 0-1 with and without histological activity, respectively. UC relapse, defined as symptomatic and endoscopic worsening, was retrospectively recorded for survival analysis. Unsupervised and differential gene expression analyses were performed, and the interaction between transcriptomics and mucosal gut microbiota was analysed based on the 16S rRNA gene sequencing profile. RESULTS: UC patients with histo-endoscopic remission showed a significantly lower risk of relapse compared to histo-endoscopic activity. Unsupervised analysis of the transcriptomic profile showed that histo-endoscopic remission and histo-endoscopic activity samples clustered with HC and MES 2-3 samples, respectively. A total of 452 host genes enriched for humoral immune response, antimicrobial defence, chemokine and TH17 signalling pathway were upregulated in histo-endoscopic activity compared to histo-endoscopic remission. A set of host genes with antimicrobial properties showed significant associations with mucosal microbiota. CONCLUSIONS: The rectosigmoid mucosa transcriptional profile of UC patients in histo-endoscopic remission resembles that of HC mucosa and confers a lower risk of relapse. These data support that the combination of histo-endoscopic remission could be the most appropriate definition of mucosal healing in UC.