Background & Aims There is an unclear relationship among bowel symptoms, excretion of unconjugated fecal bile acid (UBA), and colonic transit in irritable bowel syndrome (IBS). We measured total and main individual UBA in fecal samples of patients with IBS, and assessed relationships among stool frequency or consistency, fecal UBA (total and individual), and colonic transit. Methods In a study of 30 healthy volunteers (controls), 31 subjects with IBS with diarrhea (IBS-D), and 30 with IBS with constipation (IBS-C) were placed on 4-day diets containing 100 g fat; we measured stool characteristics, total fecal UBA and fat levels, and overall colonic transit. We assessed univariate associations of total and individual levels of fecal UBA with phenotype (controls, IBS-D, IBS-C) using the Kruskal-Wallis test; associations between endpoints were assessed using Spearman correlations. With response surface regression models, we assessed relationships between stool, colonic transit, and fecal total and secretory UBA. Results There was a significant association between total fecal UBA and phenotype (P=.029); the association was greater for IBS-D than IBS-C, compared with controls. Fecal levels of primary UBAs (cholic and chenodeoxycholic acids) were higher in subjects with IBS-D, compared with controls (both P<.01). Levels of fecal secretory UBAs (chenodeoxycholic acids, P=.019; deoxycholic acid, P=.025) were lower in subjects with IBS-C compared with controls, whereas levels of the nonsecretory UBA, lithocholic acid, were higher (P=.020). There were significant univariate associations between stool number and form and total fecal UBA (including percentages of lithocholic acid, chenodeoxycholic acids, and cholic acid), fecal fat, and colonic transit at 24 and 48 h after eating. In the regression models, the relative contribution of colonic transit was consistently greater, and largely independent of the contribution of bile acids. Conclusions Measurements of individual UBAs identify changes associated with stool characteristics in patients with IBS; these effects are independent of the effects of colonic transit.

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The systematic review and meta-analysis supports an association between optimally measured delayed gastric emptying and UGI Sx.

Running title: Network meta-analysis of pharmacological agents for treatment of CIC Word count: 3745 (excluding abstract, summary box, acknowledgements, disclosures, references, table and figure legends) Key words: bisacodyl, elobixibat, linaclotide, lubiprostone, picosulfate, polyethylene glycol, prucalopride, tegaserod, velusetrag Abbreviations: chronic idiopathic constipation (CIC) numbers needed to treat (NNT) sodium picosulfate (NaP) polyethylene glycol (PEG) complete spontaneous bowel movements (CSBM) spontaneous bowel movements (SBM) weighted mean difference (WMD) confidence interval (CI) Study Selection: Phase IIB and phase III randomized, placebo-controlled trials (RCT) of ≥4weeks' treatment for CIC in adults with Rome II or III criteria for functional constipation; trials included at least 1 of 4 endpoints. Data Extraction and Synthesis:Two investigators independently evaluated all full text articles that met inclusion criteria and extracted data for primary and secondary endpoints, risk of bias and quality of evidence.Outcomes: Primary endpoints were ≥3 complete spontaneous bowel movements (CSBM)/week and increase over baseline by ≥1 CSBM/week. Secondary endpoints were change from baseline (∆ b ) in the number of SBM/week and ∆ b CSBM/week.Results: Twenty-one RCTs (9189 patients) met inclusion and endpoint criteria: 9 prucalopride, 3 lubiprostone, 3 linaclotide, 2 tegaserod, 1 each velusetrag, elobixibat, bisacodyl and sodium picosulphate (NaP). All pre-specified endpoints were unavailable in 4 polyethylene glycol studies. Bisacodyl, NaP, prucalopride and velusetrag were superior to placebo for the ≥3 CSBM/week endpoint. No drug was superior at improving the primary endpoints on network meta-analysis. Bisacodyl appeared superior to the other drugs for the secondary endpoint, ∆ b in number of SBM/week.

Altered bile acid (BA) concentrations in the colon may cause diarrhea or constipation. BA malabsorption (BAM) accounts for >25% of patients with irritable bowel syndrome (IBS) with diarrhea and chronic diarrhea in Western countries. As BAM is increasingly recognized, proper diagnostic methods are desired in clinical practice to help direct the most effective treatment course for the chronic bowel dysfunction. This review appraises the methodology, advantages and disadvantages of 4 tools that directly measure BAM: 14C-glycocholate breath and stool test, 75Selenium HomotauroCholic Acid Test (SeHCAT), 7 α-hydroxy-4-cholesten-3-one (C4) and fecal BAs. 14C-glycocholate is a laborious test no longer widely utilized. 75SeHCAT is validated, but not available in the United States. Serum C4 is a simple, accurate method that is applicable to a majority of patients, but requires further clinical validation. Fecal measurements to quantify total and individual fecal BAs are technically cumbersome and not widely available. Regrettably, none of these tests are routinely available in the U.S., and a therapeutic trial with a BA binder is used as a surrogate for diagnosis of BAM. Recent data suggest there is an advantage to studying fecal excretion of the individual BAs and their role in BAM; this may constitute a significant advantage of the fecal BA method over the other tests. Fecal BA test could become a routine addition to fecal fat measurement in patients with unexplained diarrhea. In summary, availability determines the choice of test among C4, SeHCAT and fecal BA; more widespread availability of such tests would enhance clinical management of these patients.

Overall, the test with the highest diagnostic yield conducted in the largest number of studies was SeHCAT retention, which is not widely available in many countries outside Europe and Canada. Using different diagnostic tests, 25% (average) of patients with lower FBD with diarrhoea has evidence of idiopathic BAD. These tests serve to identify idiopathic BAD among patients with FBD with diarrhoea. Further studies are required to appraise the performance characteristics of tests for idiopathic BAD.

In this systematic review, we investigate the epidemiology, pathogenesis, risk factors, clinical manifestations, diagnosis and treatment of COVID-19-associated pulmonary aspergillosis (CAPA). We identified 85 cases from 22 studies. The frequency of CAPA is currently unknown but ranges between <5% to >30% in different case series; the possibility of colonization rather than invasive disease is the most important confounder. The vast majority of patients with CAPA did not have any of the classic host risk factors, such as immunosuppression from organ transplant or neutropenia, although a significant proportion (46%) had received corticosteroids. Age, pulmonary comorbidities and male sex were associated with higher mortality. Patients treated with voriconazole had numerically lower case-fatality rate. Clinical vigilance for CAPA is advisable in critically ill patients with COVID-19 who are not improving, even those who do not meet classic host criteria for invasive mycoses, especially if they are receiving corticosteroids. A thorough, multi-faceted diagnostic work-up and early initiation of a mold-active triazole may be lifesaving. Further research studies using standardized, uniform definitions of invasive disease and colonization are urgently needed.