Inflammatory bowel disease: The role of commensal microbiome in immune regulation / Enfermedad inflamatoria intestinal: el rol de microbioma comensal en la regulación inmune

The incidence of inflammatory bowel disease (IBD) is increasing. Microbiome is one of the most important factors in its development and affects the different clinical outcomes of IBD patients depending on its composition and different alterations. We conducted a systematic review to discuss the association between microbiome and IBD in terms of immune regulation, and therapies that can modify microbiota. A comprehensive systematic literature search was performed through April 2020 in PubMed, Web of Science, the Cochrane Library, and clinicaltrials.gov. Inclusion criteria required IBD immune regulation and alternate therapeutics for IBD. This analysis helps explain the multifactorial origin of microbiome diversity including normal immune regulation, immune pathophysiology of IBD, and shows the evidence of several therapeutic targets to change microbiome in patients with IBD, such as prebiotics, probiotics, antibiotics, fecal microbiota transplant, and others.(AU)

La incidencia en enfermedad inflamatoria intestinal (EII) va en aumento. El microbioma es uno de los factores más importantes en su desarrollo y afecta los diferentes escenarios clínicos en pacientes con EII dependiendo de su composición y diferentes alteraciones. Se realizó una revisión sistemática para discutir la asociación entre el microbioma y EII relacionado con inmunorregulación y las terapias que pueden modificar la microbiota. Se realizó una búsqueda en la literatura hasta abril de 2020 en Pubmed, Web of Science, Cochrane library y clinicaltrials.gov. La inclusión del material requiere EII, inmunorregulación y las terapias alternativas para EII. Este estudio ayuda a explicar el origen multifactorial de la diversidad del microbioma incluyendo la inmunorregulación normal, fisiopatología inmuno de EII y muestra la evidencia de diferentes blancos terapéuticos para cambiar el microbioma en pacientes con EII como prebióticos, probióticos, antibióticos, trasplante de materia fecal, entre otros.(AU)

A systematic review and functional bioinformatics analysis of genes associated with Crohn's disease identify more than 120 related genes.

BACKGROUND: Crohn's disease is one of the two categories of inflammatory bowel diseases that affect the gastrointestinal tract. The heritability estimate has been reported to be 0.75. Several genes linked to Crohn's disease risk have been identified using a plethora of strategies such as linkage-based studies, candidate gene association studies, and lately through genome-wide association studies (GWAS). Nevertheless, to our knowledge, a compendium of all the genes that have been associated with CD is lacking. METHODS: We conducted functional analyses of a gene set generated from a systematic review where genes potentially related to CD found in the literature were analyzed and classified depending on the genetic evidence reported and putative biological function. For this, we retrieved and analyzed 2496 abstracts comprising 1067 human genes plus 22 publications regarding 133 genes from GWAS Catalog. Then, each gene was curated and categorized according to the type of evidence associated with Crohn's disease. RESULTS: We identified 126 genes associated with Crohn's disease risk by specific experiments. Additionally, 71 genes were recognized associated through GWAS alone, 18 to treatment response, 41 to disease complications, and 81 to related diseases. Bioinformatic analysis of the 126 genes supports their importance in Crohn's disease and highlights genes associated with specific aspects such as symptoms, drugs, and comorbidities. Importantly, most genes were not included in commercial genetic panels suggesting that Crohn's disease is genetically underdiagnosed. CONCLUSIONS: We identified a total of 126 genes from PubMed and 71 from GWAS that showed evidence of association to diagnosis, 18 to treatment response, and 41 to disease complications in Crohn's disease. This prioritized gene catalog can be explored at http://victortrevino.bioinformatics.mx/CrohnDisease .

Prevalence of Gastrointestinal Symptoms, Severity of Dysphagia, and Their Correlation with Severity of Amyotrophic Lateral Sclerosis in a Mexican Cohort.

OBJECTIVES: Our study aimed to identify the prevalence and severity of gastrointestinal (GI) symptoms and dysphagia in patients with amyotrophic lateral sclerosis (ALS) and to assess whether a correlation exists between these symptoms and the severity of ALS progression. METHODS: The presence and severity of GI symptoms and dysphagia were identified by means of the Gastrointestinal Symptom Rating Scale (GSRS) and the Functional Outcome Swallowing Scale (FOSS). The Revised ALS Functional Rating Scale (ALSFRS-R) was utilized to determine the severity of ALS. Analysis of data was performed with Spearman correlations in semi-qualitative variables of clinical scales. ALSFRS-R scores were divided into 2 categories: those with mild to moderate ALS (≥40-30 points) and patients with moderate to advanced ALS (29-≤20 points). RESULTS: We studied 43 patients with definite ALS. The most frequent GI symptoms were constipation (60.5%), rectal tenesmus (57.5%), hard stools (55.0%), and borborygmus (42.5%). The moderate to advanced ALS stage was correlated with constipation (r = 0.334; p = 0.028), acid regurgitation (r = 0.384; p = 0.013), eructation (r = 0.334; p = 0.032), rectal tenesmus (r = 0.498; p = 0.001), and functional dysphagia (r = 0.656; p = <0.001). CONCLUSIONS: Early detection of these GI symptoms can guide timely therapeutic decisions to avoid weight loss, a predictor for worse prognosis. This study highlights the relevance of the detection of these symptoms in ALS patients who score ≤29 points in the ALSFRS-R scale to establish an appropriate treatment, prevent systemic complications, provide more comfort, and improve quality of life.

Incidence and prevalence of inflammatory bowel disease in Mexico from a nationwide cohort study in a period of 15 years (2000-2017).

Despite the worldwide increasing incidence and prevalence of Inflammatory Bowel Disease (IBD), our knowledge about it in Mexico is still limited. The aim of this study is to describe the incidence and prevalence of IBD as well as its clinical and socio-demographical characteristics in Mexico from a nation-wide perspective.Multicenter nation-wide cohort study that included 42 IBD clinics from all over the country that participated with electronically register of the new cases over 17 years as well as all known existing cases together with their clinical and socio-demographical characteristics from patients with IBD (ulcerative colitis [UC], Crohn disease [CD], and inflammatory bowel disease unclassified [IBDU]). The data collection was conducted between January and October 2017. Incidence, prevalence, and mean incidence over 2 decades were then calculated. Data base was analyzed using SPSS v24 program SPSS (version 24, IBM Corp., Armonk, NY, USA).A total of 2645 patients with IBD were registered. The crude incidence rates of IBD, UC, and CD, respectively, were 0.21, 0.16, and 0.04 cases per 100,000-person year. The highest incidence was registered in the year 2015, compared with to the previous years. The mean incidence of IBD has increased steadily from 0.05 to 0.21 per 100,000 person-years over the past 15 years (P = .06). The incidence of IBD new cases have increased significantly throughout the last 16 years, 5.9-fold for IBD, 5.3-fold for UC, and 9.5-fold for CD. The prevalence rates of IBD, UC, and CD, respectively, were 1.83, 1.45, and 0.34 cases per 100,000-person-year.This is the first study from a nation-wide perspective that demonstrated a significant increase of prevalence and incidence of IBD in Mexico in the last 15 years.

Targeted Physician Education and Standardizing Documentation Improves Documented Reporting with Inflammatory Bowel Disease Quality Measures in a Large Academic and Private Practice.

BACKGROUND: Prior studies have shown poor compliance with quality measures for IBD at academic and private practices. We sought to provide focused interventions to improve compliance and documentation with the IBD measures. METHODS: Two centers, academic practice (AP) and private practice (PP), initially reviewed their compliance with eight established IBD quality measures in consecutive charts. A multi-faceted intervention was developed to improve awareness and documentation of these measures. The initial data and the quality measures were reviewed at a group meeting. Following this, a handout summarizing the measures was placed in each exam room. The AP added a new screen to the EHR that summarized the relevant IBD history, while the PP added a new template that was filled out and imported into the charts. Three months after this intervention, charts were reviewed for compliance with the measures. RESULTS: The intervention cohort consisted of 768 patients (AP = 569/PP = 199) compared to the initial cohort of 566 patients (AP = 367/PP = 199). Improvement was seen throughout all measures compared to the initial cohort. The AP reported compliance with all relevant measures in 21% and the PP in 60% compared to 7 and 10% in the initial cohort. PP had ≥ 75% compliance with every measure, of which only assessment for bone loss and pneumococcal vaccination was under 80%. In contrast, the AP compliance ranged from 35 to 100% with assessment for bone loss, influenza, and pneumococcal vaccination scoring lowest. CONCLUSION: Our study demonstrates that focused low-cost interventions can significantly improve compliance with IBD quality measures in different practice settings.

Biology of anti-TNF agents in immune-mediated inflammatory diseases: therapeutic implications.

Biologics are increasingly being used to modify the course of immune-mediated inflammatory diseases. Some main agents are monoclonal antibodies and a fusion-protein that target TNF. This group includes adalimumab, infliximab, certolizumab pegol, golimumab and etanercept. Although the efficacy of anti-TNFs is supported by numerous randomized clinical trials, their pharmacokinetics depend on many factors, in particular immunogenicity, which can cause marked and rapid clearance and a consequent decrease in efficacy. Kinetics involve receptors that recognize the Fc fragment of the antibody and are responsible for various processes. Pharmacological advances permit optimizing the pharmacokinetics of anti-TNFs. In this review, we examine the kinetics of anti-TNF biologics, and consequent therapeutic implications, and overview some latest developments in the field. First draftsubmitted: 17 May 2016; Accepted for publication: 15 September2016; Published online: 14 October 2016.

Poor Documentation of Inflammatory Bowel Disease Quality Measures in Academic, Community, and Private Practice.

BACKGROUND & AIMS: Quality measures are used to standardize health care and monitor quality of care. In 2011, the American Gastroenterological Association established quality measures for inflammatory bowel disease (IBD), but there has been limited documentation of compliance from different practice settings. METHODS: We reviewed charts from 367 consecutive patients with IBD seen at academic practices, 217 patients seen at community practices, and 199 patients seen at private practices for compliance with 8 outpatient measures. Records were assessed for IBD history, medications, comorbidities, and hospitalizations. We also determined the number of patient visits to gastroenterologists in the past year, whether patients had a primary care physician at the same institution, and whether they were seen by a specialist in IBD or in conjunction with a trainee, and reviewed physician demographics. A univariate and multivariate statistical analysis was performed to determine which factors were associated with compliance of all core measures. RESULTS: Screening for tobacco abuse was the most frequently assessed core measure (89.6% of patients; n = 701 of 783), followed by location of IBD (80.3%; n = 629 of 783), and assessment for corticosteroid-sparing therapy (70.8%; n = 275 of 388). The least-frequently evaluated measures were pneumococcal immunization (16.7% of patients; n = 131 of 783), bone loss (25%; n = 126 of 505), and influenza immunization (28.7%; n = 225 of 783). Only 5.8% of patients (46 of 783) had all applicable core measures documented (24 in academic practice, none in clinical practice, and 22 in private practice). In the multivariate model, year of graduation from fellowship (odds ratio [OR], 2.184; 95% confidence interval [CI], 1.522-3.134; P < .001), year of graduation from medical school (OR, 0.500; 95% CI, 0.352-0.709; P < .001), and total number of comorbidities (OR, 1.089; 95% CI, 1.016-1.168; P = .016) were associated with compliance with all core measures. CONCLUSIONS: We found poor documentation of IBD quality measures in academic, clinical, and private gastroenterology practices. Interventions are necessary to improve reporting of quality measures.

Surgery for Ulcerative Colitis Is Associated with a High Rate of Readmissions at 30 Days.

BACKGROUND: Currently, the predictors of readmission after colectomy specifically for ulcerative colitis (UC) are poorly investigated. We sought to determine the rates and predictors of 30-day readmissions after colectomy for UC. METHODS: Patients undergoing total proctocolectomy and end ileostomy, abdominal colectomy with end ileostomy, proctocolectomy with ileoanal pouch anastomosis (IPAA) formation and diverting ileostomy, one stage IPAA, or abdominal colectomy with ileorectal anastomosis at a tertiary care center between January 2002 and January 2012 for UC were included. Patients were identified using ICD-9 code 556.x. Each record was manually reviewed. The electronic record system was reviewed for demographic information, medical histories, UC history, medications, and data regarding the admission and discharge. Charts were reviewed for readmissions within 30 days of surgery. Univariate and multivariate analyses were performed using Stata v.13. RESULTS: Two hundred nine patients with UC underwent a colectomy. Forty-three percent had a proctocolectomy with IPAA and diverting ileostomy and 32% had abdominal colectomy with end ileostomy. Seventy-six percent of surgeries were due to failure of medical therapy and 68% of patients were electively admitted for surgery. Thirty-two percent (n = 67/209) of the cohort was unexpectedly readmitted within 30 days. In multivariate model, proctocolectomy with IPAA and diverting ileostomy (odds ratio [OR] = 2.11; 95% CI, 1.06-4.19; P = 0.033) was the only significant predictor of readmission. Hospital length of stay >7 days (OR = 1.82; 95% CI, 0.98-3.41; P = 0.060), presence of limited UC (OR = 2.10; 95% CI, 0.93-4.74; P = 0.074), and steroid before admission (OR = 1.69; 95% CI, 0.90-3.2; P = 0.100) trended toward significance. CONCLUSIONS: Surgery for UC is associated with a high rate of readmission. Further prospective studies are necessary to determine the means to reduce these readmissions.

Documented compliance with inflammatory bowel disease quality measures is poor.

BACKGROUND AND AIMS: Quality metrics allows health care to be standardized and monitored. The American Gastroenterological Association (AGA) established quality metrics for inflammatory bowel disease (IBD) in 2011, but compliance is unknown. METHODS: Patients with IBD seen in the gastroenterology clinics at a tertiary care medical center during April 2013 were included. Charts were reviewed for the current state of compliance with the publicized AGA measures over the prior 12 months. Records were assessed for type of IBD, year of diagnosis, number of medications, comorbidities, hospitalizations and gastroenterology clinic visits in the last year, presence of primary care physician (PCP) at the institution, and involvement of a specialist in IBD or a trainee. Univariate and multivariate logistic regression analyses were done using SPSS. RESULTS: Only 6.5 % (24/367) of patients had all applicable core measures documented. In univariate analysis, year of IBD diagnosis (p = 0.014), number of comorbidities (p = 0.024), seen by a specialist in IBD (p = 0.002), seen by a gastroenterology fellow or resident (p = 0.034), and having a PCP at the institution (p = 0.006) were significant. In multivariate analysis, seen by a specialist in IBD (5.36, 95 % CI 1.22-23.63, p = 0.027), having a PCP at the institution (3.24, 95 % CI 1.23-8.54, p = 0.018), and year of IBD diagnosis (0.967, 95 % CI 0.937-0.999, p = 0.042) remained significant. Screening for tobacco abuse was the most frequently assessed (96 %, n = 352/367) core measure, while pneumococcal immunization (21 %, n = 76/367) was the least. CONCLUSION: Our study demonstrates poor compliance with IBD quality metrics. Additional studies are needed to determine the causes of failure to comply with the quality metrics.

Proactive therapeutic concentration monitoring of infliximab may improve outcomes for patients with inflammatory bowel disease: results from a pilot observational study.

BACKGROUND: Infliximab (IFX) is effective in the treatment of inflammatory bowel disease; however, the effect is often not durable. It is unknown if proactive therapeutic concentration monitoring (TCM) of IFX improves outcomes. METHODS: This is a retrospective observational study examining the use of proactive TCM and titration of IFX to a target concentration for patients with inflammatory bowel disease in clinical remission at a tertiary care center. The primary aim was to describe the clinical course of patients who had proactive TCM. A secondary analysis was done to assess if this strategy was superior to the standard of care. RESULTS: Forty-eight patients were identified as having proactive TCM. Fifteen percent had an initial undetectable trough concentration. Twenty-five percent (12 of 48) of patients escalated IFX after the first proactive TCM while 15% (7 of 48) of patients de-escalated IFX therapy over the study period. A control group of 78 patients was identified. Patients who had proactive TCM had a greater probability of remaining on IFX than controls (hazard ratio, 0.3; 95% confidence interval, 0.1-0.6; log rank test; P = 0.0006). The probability of remaining on IFX was greatest for patients who achieved a trough concentration >5 µg/mL (hazard ratio, 0.03; 95% confidence interval, 0.01-0.1; P < 0.0001 versus trough <5 µg/mL). Fewer patients in the proactive TCM group stopped IFX (10% versus 31%, P = 0.009). CONCLUSIONS: In this pilot observational study, proactive TCM of IFX frequently identified patients with low or undetectable trough concentrations and resulted in a greater probability of remaining on IFX.

Isolation of rare coagulase-negative isolates in immunocompromised patients: Staphylococcus gallinarum, Staphylococcus pettenkoferi and Staphylococcus pasteuri.

Herein, we describe the isolation of Staphylococcus pasteuri, Staphylococcus pettenkoferi and Staphylococcus gallinarum and summarize the clinical characteristics of five patients. Cases were identified over a 2-year surveillance period that identified the respective strains using microbiologic and molecular methods. These data suggest that rare coagulase-negative staphylococcal infections may be under-diagnosed due to difficulties associated with routine clinical laboratory diagnostic methods.

Microbiological and molecular characterization of human clinical isolates of Staphylococcus cohnii, Staphylococcus hominis, and Staphylococcus sciuri.

BACKGROUND: The incidence of coagulase-negative staphylococci reported as causative agents of nosocomial infections has risen in the last decade. The aim of this study was to characterize biofilm formation, antibiotic resistance, SCCmec type, and genetic relatedness in clinical isolates of Staphylococcus cohnii, Staphylococcus hominis, and Staphylococcus sciuri recovered from humans. METHODS: Clinically relevant isolates of S. cohnii (n = 15), S. hominis (n = 9), and S. sciuri (n = 6), were collected from patients. Biofilm formation was evaluated using crystal violet staining, drug susceptibility was assessed using the broth microdilution method, and methicillin resistance was measured using the cefoxitin disk test. SCCmec was typed using 2 different methodologies, and genetic relatedness was determined by pulsed-field gel electrophoresis (PFGE). RESULTS: Sixty percent (9/15) of S. cohnii, 33% (3/9) of S. hominis, and 50% (3/6) of S. sciuri isolates were categorized as weak producers of biofilm. None of the isolates were resistant to vancomycin or linezolid. All 3 species showed a high resistance (> 66%) to ampicillin, levofloxacin, erythromycin, and ceftriaxone, and the majority of the isolates were methicillin-resistant. PFGE revealed that the S. cohnii isolates comprised 1 dominant clone. CONCLUSIONS: The S. cohnii, S. hominis, and S. sciuri isolates analyzed in this study showed a high methicillin resistance and resistance to other antimicrobials. The results of this study strongly suggest that coagulase-negative staphylococci harbour new SCCmec elements. We report the first case of a clone of S. cohnii associated with human disease.

The amount of alcohol consumption negatively impacts short-term mortality in Mexican patients with alcoholic hepatitis.

OBJECTIVES: Mexicans have an increased rate of alcohol abuse and alcoholic liver disease. Factors influencing the severity of alcoholic hepatitis (AH) in Mexicans are unknown. The aims of the present study were to identify the prognostic factors of short-term mortality in Mexican patients with AH and to validate the existing prognostic models. METHODS: One hundred seventy-five consecutive patients with AH were recruited from four hospital centers in Mexico. Demographic, clinical, and biochemical parameters were obtained at admission. Univariate and multivariate logistic regression analyses were used for the identification of prognostic factors. The accuracy of different models was evaluated by their area under the receiver operating characteristic (AUROC) curve and comparative risk analysis was performed using the Kaplan-Meier method. RESULTS: Age, serum creatinine, serum bilirubin, leukocyte count, and alcohol consumption >120 g/day were independently associated with short-term mortality. The impact of alcohol consumption was significant among patients with severe AH (48 vs. 72% risk of death, P=0.03). The AUROC (95% confidence interval) curves for the different scores were Maddrey's discriminant function 0.79 (0.72-0.86); model for end-stage liver disease (MELD) 0.83 (0.75-0.89); Glasgow AH score 0.77 (0.70-0.84); and age-bilirubin-international normalized ratio-creatinine (ABIC) score 0.82 (0.75-0.88). The ABIC score allowed an accurate stratification into three different risk subgroups with 13%, 50%, and 81% mortality rate at 90 days (P<0.001). CONCLUSIONS: The amount of alcohol consumption has a negative impact on short-term mortality among Mexicans with AH. The ABIC score is useful and comparable with MELD score for the prognostic stratification of these patients.