Medication use and microscopic colitis

Background: Microscopic colitis is an increasingly common cause of watery diarrhoea. Several classes of medications have been associated with microscopic colitis in prior studies. Aims: To determine the association between the use of previously implicated medications and microscopic colitis. Methods: This was a case-control study of patients referred for elective, outpatient colonoscopy for diarrhoea. Patients were excluded for inflammatory bowel disease, C difficile, or other infectious diarrhoea. Colon biopsies were reviewed by the study pathologist and patients were classified as microscopic colitis cases or non-microscopic colitis controls. Results: The study population included 110 microscopic colitis cases and 252 controls. The cases were older, better educated and more likely to be female. Cases reported a greater number of loose, watery, or liquid stools, nocturnal stools, more urgency and weight loss compared to controls. There was no association with proton pump inhibitors (PPIs), adjusted OR (aOR) 0.66, 95% CI 0.38-1.13 or nonsteroidal anti-inflammatory drugs, aOR 0.68, 95% CI 0.40-1.17. Cholecystectomy was less common in cases, aOR 0.33, 95% CI 0.17-0.64, but microscopic colitis cases had more frequent bowel movements following cholecystectomy. Conclusion: Compared to similar patients with diarrhoea, cases with microscopic colitis were not more likely to have taken previously implicated medications. They had more diarrhoea following cholecystectomy, suggesting that bile may play a role in symptoms or aetiology. We conclude that the appropriate choice of controls is crucial to understanding risk factors for microscopic colitis

Obesity is associated with decreased risk of microscopic colitis in women

BACKGROUND Microscopic colitis is a leading cause of diarrhea in the older adults. There is limited information about risk factors. We hypothesized that obesity would be associated with microscopic colitis. AIM To examine the association between obesity and microscopic colitis in men and women undergoing colonoscopy. METHODS We conducted a case-control study at the University of North Carolina Hospitals. We identified and enrolled men and women referred for elective, outpatient colonoscopy for chronic diarrhea. We excluded patients with a past diagnosis of Crohn's disease or ulcerative colitis. A research pathologist reviewed biopsies on every patient and classified them as microscopic colitis cases or non-microscopic colitis controls. Patients provided information on body weight, height and exposure to medications via structured interviews or Internet based forms. The analysis included 110 patients with microscopic colitis (cases) and 252 nonmicroscopic colitis controls. Multivariable analyses were performed using logistic regression to estimate odds ratios and 95% confidence intervals. RESULTS Cases were older and more likely than controls to be white race. Study subjects were well educated, but cases were better educated than controls. Cases with microscopic colitis had lower body mass index than controls and reported more weight loss after the onset of diarrhea. Compared to patients who were normal or under-weight, obese (BMI > 30 kg/m2) patients were substantially less likely to have microscopic colitis after adjusting for age and education, adjusted OR (aOR) 0.35, 95% confidence interval (CI) 0.18-0.66). When stratified by sex, the association was limited to obese women, aOR 0.21, 95%CI: 0.10-0.45. Patients with microscopic colitis were more likely to report weight loss after the onset of diarrhea. After stratifying by weight loss, there remained a strong inverse association between obesity and microscopic colitis, aOR 0.33, 95%CI: 0.10 - 1.11 among the patients who did not lose weight. Ever use of birth control pills was associated with lower risk of microscopic colitis after adjusting for age, education and BMI, aOR 0.38, 95%CI: 0.17-0.84. CONCLUSION Compared to controls also seen for diarrhea, microscopic colitis cases were less likely to be obese. Mechanisms are unknown but could involve hormonal effects of obesity or the gut microbiome

Intraepithelial and Lamina Propria Lymphocytes Do Not Correlate with Symptoms or Exposures in Microscopic Colitis

INTRODUCTION:Microscopic colitis, a common cause of diarrhea, is characterized by a largely normal appearance of the mucosa but increased numbers of lymphocytes in the epithelium and lamina propria on microscopy. We sought to determine whether T-cell percentage was associated with exposures or symptoms.METHODS:We conducted a case-control study that enrolled patients referred for colonoscopy for diarrhea. Patients were classified as microscopic colitis cases or controls by an experienced pathologist. Participants provided information on symptoms and exposures during a telephone or internet survey. Research biopsies from the ascending colon and descending colon were examined using immunofluorescence stains for CD3, CD8, and FOXP3 to determine percent T cells per total epithelial or lamina propria cells. Digital images were analyzed by regions of interest using Tissue Studio.RESULTS:There were 97 microscopic colitis cases and 165 diarrhea controls. There was no association between demographic factors and percentage of intraepithelial or lamina propria T cells. In cases, the mean percent T cells were similar in the right colon and left colon. There was no association between mean percent T cells and stool frequency or consistency. There was no association with irritable bowel syndrome, abdominal pain, or medications purported to cause microscopic colitis.DISCUSSION:The lack of association between the density of T cells and medications raises further doubts about their role in disease etiology. Loose and frequent stools in patients with microscopic colitis are not correlated with T-cell density

Microbial Associations With Microscopic Colitis

INTRODUCTION: Microscopic colitis is a relatively common cause of chronic diarrhea and may be linked to luminal factors. Given the essential role of the microbiome in human gut health, analysis of microbiome changes associated with microscopic colitis could provide insights into the development of the disease. METHODS: We enrolled patients who underwent colonoscopy for diarrhea. An experienced pathologist classified patients as having microscopic colitis (n = 52) or controls (n = 153). Research biopsies were taken from the ascending (ASC) and descending (DES) colon, and the microbiome was characterized with Illumina sequencing. We analyzed the associations between microscopic colitis and microbiome with a series of increasingly complex models adjusted for a range of demographic and health factors. RESULTS: We found that alpha diversity was significantly lower in cases with microscopic colitis compared with that in controls in the DES colon microbiome. In the DES colon, a series of models that adjusted for an increasing number of covariates found taxa significantly associated with microscopic colitis, including Proteobacteria that was enriched in cases and Collinsella that was enriched in controls. While the alpha diversity and taxa were not significantly associated with microscopic colitis in the ASC colon microbiome, the inference P values based on ASC and DES microbiomes were highly correlated. DISCUSSION: Our study demonstrates an altered microbiome in cases with microscopic colitis compared with that in controls. Because both the cases and controls experienced diarrhea, we have identified candidate taxa that could be mechanistically responsible for the development of microscopic colitis independent of changes to the microbial community caused by diarrhea

Dietary calcium and risk of microscopic colitis

BACKGROUND: Microscopic colitis is an increasingly common cause of watery diarrhea particularly in older individuals. The role of diet in microscopic colitis has received little study. METHODS: We conducted a case-control study at a single institution enrolling patients referred for elective, outpatient colonoscopy for diarrhea. Patients were classified as microscopic colitis cases or non-microscopic colitis controls following review of colon biopsies by one research pathologist. Study subjects were interviewed by a trained telephone interviewer using a validated food frequency questionnaire. Adherent microbes were evaluated from colonic biopsies using 16s rRNA sequencing. RESULTS: The study population included 106 microscopic colitis cases and 215 controls. Compared to controls, the cases were older, better educated and more likely to be female. Microscopic colitis cases had lower body mass index (BMI) and were more likely to have lost weight. Subjects in the highest quartile of dietary calcium intake had a lower risk of microscopic colitis compared to the lowest quartile, adjusted odds ratio 0.22, 95% confidence interval 0.07-0.76). The findings were not explained by dairy intake, body mass index or weight loss. We found that dietary calcium intake had significant associations with the abundance of Actinobacteria and Coriobacteriales in the microbial community of colonic biopsies. CONCLUSIONS: Compared to patients with diarrhea, microscopic colitis cases had lower intake of dietary calcium. Diet can be associated with alterations in the gut microbiota and with luminal factors that could affect risk for microscopic colitis

Rapid Recurrence of Eosinophilic Esophagitis Activity After Successful Treatment in the Observation Phase of a Randomized, Double-Blind, Double-Dummy Trial

Background & Aims: Eosinophilic esophagitis (EoE) is chronic and recurs if treatment is discontinued. We aimed to determine rates of recurrence, and whether initial treatment with oral viscous budesonide (OVB) resulted in less recurrence than fluticasone from a multidose inhaler (MDI). Methods: This was the observation phase of a randomized, double-blind, double-dummy trial comparing OVB with MDI for initial EoE treatment. Subjects with a histologic response (<15 eosinophils/high-power field) in the trial entered an observation phase in which treatment was discontinued and symptoms were monitored. Patients underwent an endoscopy or a biopsy when symptoms recurred or at 1 year. We analyzed time to symptom recurrence and assessed endoscopic severity and histologic relapse (≥15 eosinophils/high-power field) at follow-up endoscopy. Results: Thirty-three of the 58 subjects (57%) had symptom recurrence before 1 year. The overall median time to symptom recurrence was 244 days. There was no difference in the rate of symptom recurrence for subjects treated with OVB vs MDI (hazard ratio, 1.04; 95% CI, 0.52–2.08). At symptom recurrence, 78% of patients had histologic relapse. The patients had significant increases in mean Dysphagia Symptom Questionnaire score (3.8 vs 8.7; P < .001), and the EoE Endoscopic Reference Score (1.3 vs 4.6; P < .001) compared with end of treatment. Conclusions: EoE disease activity recurred rapidly after initial histologic response to topical steroids (either OVB or MDI). Because most subjects had recurrent endoscopic and histologic signs not reliably detected by symptoms, maintenance therapy should be recommended in EoE patients achieving histologic response to topical steroids. Clinicaltrials.gov no: NCT02019758

Efficacy of Budesonide vs Fluticasone for Initial Treatment of Eosinophilic Esophagitis in a Randomized Controlled Trial

Background and Aims: Topical steroid treatments for eosinophilic esophagitis (EoE) include swallowed fluticasone from a multi-dose inhaler (MDI) or oral viscous budesonide (OVB) slurry, but the 2 have never been compared. We assessed whether OVB was more effective than MDI for initial treatment of patients with EoE. Methods: In a double-blind, double-dummy trial, patients with a new diagnosis of EoE were randomly assigned to groups given 8 weeks of either OVB (1 mg/4 mL) twice daily plus a placebo inhaler (n = 56) or fluticasone MDI (880 μg) twice daily plus a placebo slurry (n = 55). Primary outcomes were post-treatment maximum eosinophil counts per high-power field (eos/hpf) and a validated dysphagia score (dysphagia symptom questionnaire [DSQ]) at week 8. Secondary outcomes included endoscopic severity (validated EoE endoscopic reference score), histologic response (<15 eos/hpf), and safety. Results: In a modified intention-to-treat analysis, the subjects had baseline peak eosinophil counts of 73 and 77 eos/hpf in the OVB and MDI groups, respectively, and DSQ scores of 11 and 8. Post-treatment eosinophil counts were 15 and 21 in the OVB and MDI groups, respectively (P =.31), with 71% and 64% achieving histologic response (P =.38). DSQ scores were 5 and 4 in the OVB and MDI groups (P =.70). Similar trends were noted for post-treatment total EoE endoscopic reference scores (2 vs 3; P =.06). Esophageal candidiasis developed in 12% of patients receiving OVB and 16% receiving MDI; oral thrush was observed in 3% and 2%, respectively. Conclusions: In a randomized clinical trial, initial treatment of EoE with either OVB or fluticasone MDI produced a significant decrease in esophageal eosinophil counts and improved dysphagia and endoscopic features. However, OVB was not superior to MDI, so either is an acceptable treatment for EoE. ClinicalTrials.gov ID NCT02019758

Abundances of the elements in the solar system

A review of the abundances and condensation temperatures of the elements and their nuclides in the solar nebula and in chondritic meteorites. Abundances of the elements in some neighboring stars are also discussed.Comment: 42 pages, 11 tables, 8 figures, chapter, In Landolt- B\"ornstein, New Series, Vol. VI/4B, Chap. 4.4, J.E. Tr\"umper (ed.), Berlin, Heidelberg, New York: Springer-Verlag, p. 560-63

On the sensitivity of the HAWC observatory to gamma-ray bursts

We present the sensitivity of HAWC to Gamma Ray Bursts (GRBs). HAWC is a very high-energy gamma-ray observatory currently under construction in Mexico at an altitude of 4100 m. It will observe atmospheric air showers via the water Cherenkov method. HAWC will consist of 300 large water tanks instrumented with 4 photomultipliers each. HAWC has two data acquisition (DAQ) systems. The main DAQ system reads out coincident signals in the tanks and reconstructs the direction and energy of individual atmospheric showers. The scaler DAQ counts the hits in each photomultiplier tube (PMT) in the detector and searches for a statistical excess over the noise of all PMTs. We show that HAWC has a realistic opportunity to observe the high-energy power law components of GRBs that extend at least up to 30 GeV, as it has been observed by Fermi LAT. The two DAQ systems have an energy threshold that is low enough to observe events similar to GRB 090510 and GRB 090902b with the characteristics observed by Fermi LAT. HAWC will provide information about the high-energy spectra of GRBs which in turn could help to understanding about e-pair attenuation in GRB jets, extragalactic background light absorption, as well as establishing the highest energy to which GRBs accelerate particles