Faecal calprotectin in the diagnosis of inflammatory bowel disease

Suspicion of inflammatory bowel disease should be raised in any patient with chronic or recurrent abdominal pain and diarrhoea. However, symptoms of inflammatory bowel disease (IBD) overlap with functional gastrointestinal disorders and those patients may not need endoscopy. Currently, colonoscopy with multiple biopsies is considered the gold standard to establish the diagnosis of IBD. Unfortunately, patient selection for endoscopy based on symptoms is not reliable. The use of guideli-nes of appropriateness for endoscopy yields significantly more significant findings but the selection criteria suffer from low specificity. Calprotectin is a calcium binding protein of neutrophil granulocytes that correlates well with neutrophil infiltration of the intestinal mucosa when measured in faeces. In the last decade, a large body of evi-dence on the diagnostic value of faecal calprotectin has accumulated and measurement of calprotectin in faeces has been suggested as a surrogate marker of intestinal inflammation. Testing of faecal calprotectin has been highly useful to distinguish organic from functional intestinal disorders in pati-ents with abdominal complaints. Additionally, faecal calprotectin has reliably identified colonic inflam-mation in patients with suspected IBD. The use of this inexpensive and widely available test in the evaluation and risk stratification in patients with abdominal complaints is likely to increase in the futu-re

Serum protein electrophoresis : an underused but very useful test

Serum protein electrophoresis is used in clinical practice to identify patients with multiple myeloma and other serum protein disorders. It is an inexpensive and easy-to-perform screening procedure. Electrophoresis separates serum proteins based on their physical properties and identifies morphologic patterns in response to acute and chronic inflammation, various malignancies, liver or renal failure, and hereditary protein disorders. For gastroenterologists, the use of serum protein electrophoresis may be helpful in the diagnosis of both common diseases with unusual presentations and rare disorders with typical presentations. Therefore, it represents an ideal screening tool

Colonic content in health and its relation to functional gut symptoms

This is the peer reviewed version of the following article: Bendezú, R. A., Barba, E., Burri, E., Cisternas, D., Accarino, A., Quiroga, S., Monclus, E., Navazo, I., Malagelada, J.-R. and Azpiroz, F. (2016), Colonic content in health and its relation to functional gut symptoms. Neurogastroenterol. Motil., 28: 849–854, which has been published in final form at [doi:10.1111/nmo.12782]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-ArchivingGut content may be determinant in the generation of digestive symptoms, particularly in patients with impaired gut function and hypersensitivity. Since the relation of intraluminal gas to symptoms is only partial, we hypothesized that non-gaseous component may play a decisive role. Methods: Abdominal computed tomography scans were evaluated in healthy subjects during fasting and after a meal (n = 15) and in patients with functional gut disorders during basal conditions (when they were feeling well) and during an episode of abdominal distension (n = 15). Colonic content and distribution were measured by an original analysis program. Key results: In healthy subjects both gaseous (87 ± 24 mL) and non-gaseous colonic content (714 ± 34 mL) were uniformly distributed along the colon. In the early postprandial period gas volume increased (by 46 ± 23 mL), but non-gaseous content did not, although a partial caudad displacement from the descending to the pelvic colon was observed. No differences in colonic content were detected between patients and healthy subjects. Symptoms were associated with discrete increments in gas volume. However, no consistent differences in non-gaseous content were detected in patients between asymptomatic periods and during episodes of abdominal distension. Conclusions & inferences: In patients with functional gut disorders, abdominal distension is not related to changes in non-gaseous colonic content. Hence, other factors, such as intestinal hypersensitivity and poor tolerance of small increases in luminal gas may be involved.Peer ReviewedPostprint (author's final draft

Value of fecal calprotectin in the evaluation of patients with abdominal discomfort: an observational study

<p>Abstract</p> <p>Background</p> <p>The evaluation of patients with abdominal discomfort is challenging and patient selection for endoscopy based on symptoms is not reliable. We evaluated the diagnostic value of fecal calprotectin in patients with abdominal discomfort.</p> <p>Methods</p> <p>In an observational study, 575 consecutive patients with abdominal discomfort referred for endoscopy to the Department of Gastroenterology & Hepatology at the University Hospital Basel in Switzerland, were enrolled in the study. Calprotectin was measured in stool samples collected within 24 hours before the investigation using an enzyme-linked immunosorbent assay. The presence of a clinically significant finding in the gastrointestinal tract was the primary endpoint of the study. Final diagnoses were adjudicated blinded to calprotectin values.</p> <p>Results</p> <p>Median calprotectin levels were higher in patients with significant findings (N = 212, median 97 μg/g, IQR 43-185) than in patients without (N = 326, 10 μg/g, IQR 10-23, P < 0.001). The area under the receiver operating characteristics curve (AUC) to identify a significant finding was 0.877 (95% CI, 0.85-0.90). Using 50 μg/g as cut off yielded a sensitivity of 73% and a specificity of 93% with good positive and negative likelihood ratios (10.8 and 0.29, respectively). Fecal calprotectin was useful as a diagnostic parameter both for findings in the upper intestinal tract (AUC 0.730, 0.66-0.79) and for the colon (AUC 0.912, 0.88-0.94) with higher diagnostic precision for the latter (P < 0.001). In patients > 50 years, the diagnostic precision remained unchanged (AUC 0.889 vs. 0.832, P = 0.165).</p> <p>Conclusion</p> <p>In patients with abdominal discomfort, fecal calprotectin is a useful non-invasive marker to identify clinically significant findings of the gastrointestinal tract, irrespective of age.</p

Herpes simplex virus colitis mimicking acute severe ulcerative colitis: a case report and review of the literature

A 60-year-old female patient with longstanding left-sided ulcerative colitis presented with symptoms mimicking an acute flare and developed a colonic perforation shortly after starting steroid treatment. Following left hemicolectomy and Hartmann's procedure, rescue treatment with infliximab was started. Within a few days, the patient developed hepatic failure. Histology and immunohistochemistry of the specimen revealed extensive necrotizing herpes simplex virus colitis, and liver biopsy demonstrated herpes simplex virus hepatitis. Sixteen days after admission, the patient died from multiorgan failure. This compelling case of severe herpes simplex virus colitis raises awareness of a rare but potentially detrimental infection in patients with inflammatory bowel disease

Visible abdominal distension in functional gut disorders : Objective evaluation

Background: Visible abdominal distension has been attributed to: (A) distorted perception, (B) intestinal gas accumulation, or (C) abdominophrenic dyssynergia (diaphragmatic push and anterior wall relaxation). Methods: A pool of consecutive patients with functional gut disorders and visible abdominal distension included in previous studies (n = 139) was analyzed. Patients (61 functional bloating, 74 constipation-predominant irritable bowel syndrome and 4 with alternating bowel habit) were evaluated twice, under basal conditions and during a self-reported episode of visible abdominal distension; static abdominal CT images were taken in 104 patients, and dynamic EMG recordings of the abdominal walls in 76, with diaphragmatic activity valid for analysis in 35. Key Results: (A) Objective evidence of abdominal distension was obtained by tape measure (increase in girth in 138 of 139 patients), by CT imaging (increased abdominal perimeter in 96 of 104 patients) and by abdominal EMG (reduced activity, i.e., relaxation, in 73 of 76 patients). (B) Intestinal gas volume was within ±300 ml from the basal value in 99 patients, and above in 5 patients, who nevertheless exhibited a diaphragmatic descent. (C) Diaphragmatic contraction was detected in 34 of 35 patients by EMG (increased activity) and in 82 of 103 patients by CT (diaphragmatic descent). Conclusions and Inferences: In most patients complaining of episodes of visible abdominal distention: (A) the subjective claim is substantiated by objective evidence; (B) an increase in intestinal gas does not justify visible abdominal distention; (C) abdominophrenic dyssynergia is consistently evidenced by dynamic EMG recording, but static CT imaging has less sensitivity

Sodium chloride vs. sodium bicarbonate for the prevention of contrast medium-induced nephropathy: a randomized controlled trial

Aims The most effective regimen for the prevention of contrast-induced nephropathy (CIN) remains uncertain. Our purpose was to compare two regimens of sodium bicarbonate with 24 h sodium chloride 0.9% infusion in the prevention of CIN. Methods and results We performed a prospective, randomized trial between March 2005 and December 2009, including 258 consecutive patients with renal insufficiency undergoing intravascular contrast procedures. Patients were randomized to receive intravenous volume supplementation with either (A) sodium chloride 0.9% 1 mL/kg/h for at least 12h prior and after the procedure or (B) sodium bicarbonate (166 mEq/L) 3 mL/kg for 1h before and 1 mL/kg/h for 6h after the procedure or (C) sodium bicarbonate (166 mEq/L) 3 mL/kg over 20min before the procedure plus sodium bicarbonate orally (500 mg per 10 kg). The primary endpoint was the change in estimated glomerular filtration rate (eGFR) within 48h after contrast. Secondary endpoints included the development of CIN. The maximum change in eGFR was significantly greater in Group B compared with Group A {mean difference −3.9 [95% confidence interval (CI), −6.8 to −1] mL/min/1.73 m2, P = 0.009} and similar between Groups C and B [mean difference 1.3 (95% CI, −1.7-4.3) mL/min/1.73 m2, P = 0.39]. The incidence of CIN was significantly lower in Group A (1%) vs. Group B (9%, P = 0.02) and similar between Groups B and C (10%, P = 0.9). Conclusion Volume supplementation with 24 h sodium chloride 0.9% is superior to sodium bicarbonate for the prevention of CIN. A short-term regimen with sodium bicarbonate is non-inferior to a 7 h regimen. ClinicalTrials.gov Identifier: NCT0013059

Swiss expert opinion: current approaches in faecal microbiota transplantation in daily practice

INTRODUCTION Faecal microbiota transplantation (FMT) is an established therapy for recurrent C. difficile infection, and recent studies have reported encouraging results of FMT in patients with ulcerative colitis. Few international consensus guidelines exist for this therapy, and thus FMT policies and practices differ among European countries. As of 2019, stool transplants are considered a non-standardised medicinal product in Switzerland, and a standardised production process requires authorisation by the Swiss Agency for Therapeutic Products. This authorisation leads to prolonged administrative procedures and increasing costs, which reduces treatment accessibility. In particular, patients with ulcerative colitis in Switzerland can only benefit from FMT off-label, even though it is a valid therapeutic option. Therefore, this study summarised the available data on FMT and established a framework for the standardised use of FMT. METHODS A panel of Swiss gastroenterologists with a special interest in inflammatory bowel disease was established to identify the current key issues of FMT. After a comprehensive review of the literature, statements were formulated about FMT indications, donor screening, stool transplant preparation and administration, and safety aspects. The panel then voted on the statements following the Delphi process; the statements were reformulated and revoted until a consensus was reached. The manuscript was then reviewed by an infectiologist (the head of Lausanne's FMT centre). RESULTS The established statements are summarised in the supplementary tables in the appendix to this paper. The working group hopes these will help standardise FMT practice in Switzerland and contribute to making faecal microbiota transplantation a safe and accessible treatment for patients with recurrent C. difficile infections and selected patients with ulcerative colitis, as well as other indications in the future

Abdominothoracic mechanisms of functional abdominal distension and correction by biofeedback

BACKGROUND & AIMS: In patients with functional gut disorders, abdominal distension has been associated with descent of the diaphragm and protrusion of the anterior abdominal wall. We investigated mechanisms of abdominal distension in these patients. METHODS: We performed a prospective study of 45 patients (42 women, 24-71 years old) with functional intestinal disorders (27 with irritable bowel syndrome with constipation, 15 with functional bloating, and 3 with irritable bowel syndrome with alternating bowel habits) and discrete episodes of visible abdominal distension. Subjects were assessed by abdominothoracic computed tomography (n = 39) and electromyography (EMG) of the abdominothoracic wall (n = 32) during basal conditions (without abdominal distension) and during episodes of severe abdominal distension. Fifteen patients received a median of 2 sessions (range, 1-3 sessions) of EMG-guided, respiratory-targeted biofeedback treatment; 11 received 1 control session before treatment. RESULTS: Episodes of abdominal distension were associated with diaphragm contraction (19% +/- 3% increase in EMG score and 12 +/- 2 mm descent; P < .001 vs basal values) and intercostal contraction (14% +/- 3% increase in EMG scores and 6 +/- 1 mm increase in thoracic antero-posterior diameter; P < .001 vs basal values). They were also associated with increases in lung volume (501 +/- 93 mL; P < .001 vs basal value) and anterior abdominal wall protrusion (32 +/- 3 mm increase in girth; P < .001 vs basal). Biofeedback treatment, but not control sessions, reduced the activity of the intercostal muscles (by 19% +/- 2%) and the diaphragm (by 18% +/- 4%), activated the internal oblique muscles (by 52% +/- 13%), and reduced girth (by 25 +/- 3 mm) (P <= .009 vs pretreatment for all). CONCLUSIONS: In patients with functional gut disorders, abdominal distension is a behavioral response that involves activity of the abdominothoracic wall. This distension can be reduced with EMG-guided, respiratory-targeted biofeedback therapy.Peer ReviewedPostprint (published version

Bone health in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are prone to reduced bone mineral density and elevated overall fracture risk. Osteopenia affects up to 40% of patients with IBD (high regional variability). Besides disease activity, IBD specialists must consider possible side effects of medication and the presence of associated diseases and extraintestinal manifestations. Osteopenia and osteoporosis remain frequent problems in patients with IBD and are often underestimated because of widely differing screening and treatment practices. Malnutrition, chronic intestinal inflammation and corticosteroid intake are the major pathophysiological factors contributing to osteoporosis. Patients with IBD are screened for osteoporosis using dual-energy X-ray absorptiometry (DXA), which is recommended for all patients with a prolonged disease course of more than three months, with repeated corticosteroid administration, aged >40 years with a high FRAX risk score or aged <40 years with multiple risk factors. From a therapeutic perspective, besides good disease control, vitamin D supplementation and glucocorticoid sparing, several specific osteological options are available: bisphosphonates, receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors (denosumab), parathyroid hormone (PTH) analogues and selective estrogen receptor modulators. This review provides an overview of the pathophysiology, diagnosis, prevention and treatment of IBD-associated bone loss