Fatigue and its associated factors in microscopic colitis

Background: Fatigue is a well-recognized symptom in patients with inflammatory bowel disease and irritable bowel syndrome (IBS), and has been associated with psychological comorbidity and impaired quality of life in both. However, features associated with fatigue in patients with microscopic colitis (MC) are less clear. Materials and methods: We conducted a cross-sectional survey of patients with a new diagnosis of MC including levels of anxiety, depression, somatization, quality of life, and IBS-type symptoms. Levels and impact of fatigue were assessed using the Inflammatory Bowel Disease Fatigue self-assessment scale. Mean scores were compared against various patient characteristics, and were also correlated with anxiety, depression, somatization, and quality-of-life scores. Results: In total, 129 patients with MC diagnosed between 2010 and 2015 returned completed postal questionnaires. Common histological subtypes were collagenous colitis (53.5%, n = 69) and lymphocytic colitis (38.8%, n = 50). Higher mean fatigue severity and impact scores were associated with the presence of irritable-bowel-syndrome-type symptoms, abnormal levels of anxiety and depression, and high levels of somatization (p < 0.0001 for all), but those reporting ongoing symptoms attributable to MC did not report significantly higher scores. There were significant positive correlations between total anxiety, depression, or somatization scores and fatigue severity and impact scores, and significant negative correlations with quality-of-life measures (p < 0.001 for all). Conclusions: Fatigue in MC appears to be associated with reporting IBS-type symptoms, psychological comorbidity and impaired quality of life. It may therefore represent an important target for treatment

Factors affecting clinical decision-making in inflammatory bowel disease and the role of point-of-care calprotectin

Objectives: Patient-reported symptoms correlate poorly with mucosal inflammation. Clinical decision-making may, therefore, not be based on objective evidence of disease activity. We conducted a study to determine factors associated with clinical decision-making in a secondary care inflammatory bowel disease (IBD) population, using a cross-sectional design. Methods: Decisions to request investigations or escalate medical therapy were recorded from outpatient clinic encounters in a cohort of 276 patients with ulcerative colitis (UC) or Crohn’s disease (CD). Disease activity was assessed using clinical indices, self-reported flare and faecal calprotectin ≥ 250 µg/g. Demographic, disease-related and psychological factors were assessed using validated questionnaires. Logistic regression was performed to determine the association between clinical decision-making and symptoms, mucosal inflammation and psychological comorbidity. Results: Self-reported flare was associated with requesting investigations in CD [odds ratio (OR) 5.57; 95% confidence interval (CI) 1.84-17.0] and UC (OR 10.8; 95% CI 1.8-64.3), but mucosal inflammation was not (OR 1.62; 95% CI 0.49-5.39; and OR 0.21; 95% CI 0.21-1.05, respectively). Self-reported flare (OR 7.96; 95% CI 1.84-34.4), but not mucosal inflammation (OR 1.67; 95% CI 0.46-6.13) in CD, and clinical disease activity (OR 10.36; 95% CI 2.47-43.5) and mucosal inflammation (OR 4.26; 95% CI 1.28-14.2) in UC were associated with escalation of medical therapy. Almost 60% of patients referred for investigation had no evidence of mucosal inflammation. Conclusions: Apart from escalation of medical therapy in UC, clinical decision-making was not associated with mucosal inflammation in IBD. The use of point-of-care calprotectin testing may aid clinical decision-making, improve resource allocation and reduce costs in IBD

Systemic inflammatory response syndrome after major abdominal surgery predicted by early upregulation of TLR4 and TLR5

OBJECTIVES To study innate immune pathways in patients undergoing hepatopancreaticobiliary surgery to understand mechanisms leading to enhanced inflammatory responses and identifying biomarkers of adverse clinical consequences. BACKGROUND Patients undergoing major abdominal surgery are at risk of life-threatening systemic inflammatory response syndrome (SIRS) and sepsis. Early identification of at-risk patients would allow tailored postoperative care and improve survival. METHODS Two separate cohorts of patients undergoing major hepatopancreaticobiliary surgery were studied (combined n = 69). Bloods were taken preoperatively, on day 1 and day 2 postoperatively. Peripheral blood mononuclear cells and serum were separated and immune phenotype and function assessed ex vivo. RESULTS Early innate immune dysfunction was evident in 12 patients who subsequently developed SIRS (postoperative day 6) compared with 27 who did not, when no clinical evidence of SIRS was apparent (preoperatively or days 1 and 2). Serum interleukin (IL)-6 concentration and monocyte Toll-like receptor (TLR)/NF-κB/IL-6 functional pathways were significantly upregulated and overactive in patients who developed SIRS (P < 0.0001). Interferon α-mediated STAT1 phosphorylation was higher preoperatively in patients who developed SIRS. Increased TLR4 and TLR5 gene expression in whole blood was demonstrated in a separate validation cohort of 30 patients undergoing similar surgery. Expression of TLR4/5 on monocytes, particularly intermediate CD14CD16 monocytes, on day 1 or 2 predicted SIRS with accuracy 0.89 to 1.0 (areas under receiver operator curves). CONCLUSIONS These data demonstrate the mechanism for IL-6 overproduction in patients who develop postoperative SIRS and identify markers that predict patients at risk of SIRS 5 days before the onset of clinical signs