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OBJECTIVE Although laryngopharyngeal reflux (LPR) is a common condition in daily practice, no gold standard exists for its diagnosis. The objective of this study was to establish a simple and reliable scoring system for evaluating LPR consisting of both subjective and objective criteria. METHODS This retrospective study includes 124 patients presenting with symptoms of LPR. In all patients, reflux symptom index (RSI), reflux finding score (RFS), oropharyngeal pH monitoring (PHM) and transnasal oesophagoscopy (TNE) were performed and rated in a special scoring system. RESULTS A Horvath Score of 4-5 for severe LPR was found in 76 patients (61%), a score of 2-3 for non-severe LPR in 38 patients (31%) and a score of 0-1 for non-existing LPR in 10 patients (8%) by combining the 4 validated diagnostic methods. CONCLUSION The proposed scoring system qualifies as a simple and reliable tool for evaluating LPR in daily practice, directly impacting patient management.

Background and aims: Anxiety and depression are prevalent in patients with inflammatory bowel diseases (IBD), especially during IBD flares. IBD therapies can profoundly affect the mood of patients with IBD. We aimed to determine the long-term impact of anti-tumor necrosis factor (anti-TNF) and immunomodulators (IM) on anxiety and depressive symptoms in IBD patients. Methods: We compared three treatment groups with IM only (group A), anti-TNF ± IM (group B) and no such therapy (group C). Patients completed the hospital anxiety and depression scale (HADS) at 1 year, 3 years, and 5 years after start of treatment. Results: In total, 581 patients with IBD (42.9% Crohn’s disease, 57.1% ulcerative colitis/IBD unclassified) participated in this study. Effects of treatment were analyzed in a mixed effects model, with and without correction for confounders. Compared with group C, group B showed a significant treatment-related improvement in both anxiety and depressive symptoms within the first 2.5 years and also thereafter. Group A showed a significant long-term improvement of anxiety and both short-term and long-term improvement in depressive symptoms. The significance of these results was maintained after correction for confounders, including corticosteroid treatment. Additionally, both groups A and B showed a significant decrease in disease activity in the first 2.5 years after start of treatment and also thereafter. Anti-TNF and IM treatment were associated with a similarly significant decrease in anxiety and depressive symptoms over an observation period of up to 5 years. Conclusion: Besides a clear benefit for disease activity, anti-TNF and IM apparently improve the mood of patients with IBD.

Background Some patients complain that eating lettuce, gives them gas and abdominal distention. Our aim was to determine to what extent the patients' assertion is sustained by evidence. Methods An in vitro study measured the amount of gas produced during the process of fermentation by a preparation of human colonic microbiota (n = 3) of predigested lettuce, as compared to beans, a high gas‐releasing substrate, to meat, a low gas‐releasing substrate, and to a nutrient‐free negative control. A clinical study in patients complaining of abdominal distention after eating lettuce (n = 12) measured the amount of intestinal gas and the morphometric configuration of the abdominal cavity in abdominal CT scans during an episode of lettuce‐induced distension as compared to basal conditions. Key Results Gas production by microbiota fermentation of lettuce in vitro was similar to that of meat (P = .44), lower than that of beans (by 78 ± 15%; P, In some patients lettuce produces abdominal distension, which is not related to gas, but rather to an uncontrolled reaction of the abdominal muscles and the diaphragm. Hence, learning to control the abdominal muscles may prevent distension with no need of dietary restrictions.

Background: Laryngopharyngeal reflux (LPR) is a prevalent disorder. The aim of the present retrospective cohort study was to evaluate oropharyngeal pH-monitoring using a novel scoring system for LPR. Methods: In a total of 180 consecutive patients with possible LPR, reflux symptom index (RSI), reflux finding score (RFS), oropharyngeal pH-monitoring and transnasal esophagoscopy were carried out for further investigation. Results: In our series, 99 (55%) patients had severe LPR, 29 (16%) cases presented with moderate and 23 (13%) with mild severity, 9 (5%) subjects revealed neutral values, and 7 (4%) individuals were alkaline, while 13 (7%) patients had no LPR. In detecting LPR, the sensitivity, specificity and accuracy of oropharyngeal pH-monitoring was 95%, 93% and 94%, respectively. Conclusion: Oropharyngeal pH-monitoring is a reliable tool in the assessment of LPR, but the pH graphs have to be precisely analyzed and interpreted in context with other validated diagnostic tests.

Background & Aims Inflammatory bowel disease (IBD) scoring systems combine patient-reported data with physicians’ observations to determine patient outcomes, but these systems are believed to have limitations. We used real-world data from a large IBD cohort in Switzerland to compare results between patients and healthcare professionals from scoring systems for Crohn’s disease (CD) and ulcerative colitis (UC). Methods We collected data from the Swiss IBD cohort, beginning in 2006, using 2453 reports for 1385 patients (52% female, 58% with CD). During office visits, physicians asked patients about signs and symptoms and recorded their answers (health care professional-reported outcomes). On a later date, patients received a questionnaire at home (independently of the medical visit), complete it, and sent it back to the data center. Patients also completed the short form 36 and IBD quality of life (QoL) questionnaires. We calculated Cohen’s kappa (κ) statistics to assess the level of agreement in scores between patients and health care professionals (Δt between reports collected less than 2 months apart). We used Spearman correlation coefficients (ρ) to compare general well-being (GWB) and QoL scores determined by patients vs health care professionals. Our primary aim was to investigate the overall and individual level of agreement on signs and symptoms reported by health care professionals vs patients. Results The best level of agreement (although moderate) was observed for number of stools last week in patients with CD (κ = 0.47), and nocturnal diarrhea in patients with UC (κ = 0.52). Agreement was low on level of abdominal pain (κ = 0.31 for patients with CD and κ = 0.37 for patients with UC) and GWB (κ = 0.23 for patients with CD and κ = 0.26 for patients with UC). Patients reported less severe abdominal pain and worse GWB (CD) or better GWB (UC) than that determined by health care professionals. Patient self-rated GWB correlated with IBD quality of life (ρ = 0.68 for patients with CD and ρ = 0.70 for patients with UC) and SF-36 physical scores (ρ = 0.55 for patients with CD and ρ = 0.60 for patients with UC); there was no correlation between health care professional-rated GWB and QoL. Conclusions In a comparison of patient vs health care provider-reported outcomes in a Swiss IBD cohort, we found that health care professionals seem to misinterpret patients’ complaints. Patients self-rated GWB correlated with QoL scores, indicating that reporting GWB in a single question is possible and relevant, but can vary based on how the data are collected.

Faecal calprotectin correlates with histological and clinical activity in inflammatory bowel disease. Gastrointestinal bleeding might also increase faecal calprotectin levels, erroneously implying intestinal inflammation; however, this possibility has not been systematically assessed.Sixteen healthy volunteers without gastrointestinal disease and normal faecal calprotectin baseline values ingested their own blood twice, either by drinking or via nasogastric tube. Quantities of 100 ml and 300 ml blood were ingested in a randomised order, with a 28-day wash-out period. Faecal calprotectin, faecal occult blood test, and the occurrence of melaena were assessed. Faecal calprotectin ≥ 50 µg/g was considered elevated.Melaena was reported by all healthy volunteers after 300 ml and by 11/15 healthy volunteers (71%) after 100 ml blood ingestion. One day after ingestion of 300 ml blood, 8/16 faecal calprotectin tests were positive compared to 1/16 at baseline (Ingestion of blood resulted in an increase in faecal calprotectin-positive tests. Gastrointestinal bleeding should be considered as a potential cause of mild faecal calprotectin elevation 50 µg/g; however, increased faecal calprotectin above 250-300 µg/g, the established cut-off for relevant intestinal inflammation in patients with inflammatory bowel disease, is rare.

Background: The knowledge about risk factors for the onset of uveitis manifestations in patients with inflammatory bowel disease (IBD) is still limited. Here, we aimed to provide an overview of the clinical factors associated with the onset of uveitis in the Swiss IBD Cohort Study (SIBDCS). Methods: We included epidemiological and clinical data from 1840 patients with Crohn’s disease (CD) and 1426 patients with ulcerative colitis (UC) followed up in the SIBDCS between 2006 and 2018. Associations between disease characteristics and uveitis were assessed in univariate and multivariate analyses. Results: Overall, we identified 285 patients with uveitis. Uveitis was more frequent in patients with CD (11.1%; 205 of 1635) than UC (5.6%; 80 of 1346; odds ratio 2.11, p Conclusions: Our data demonstrate that uveitis in IBD occurs more often in CD as well as in women and is associated with a more severe disease course. This might guide physicians’ awareness in at-risk patients to the presence of uveitis extraintestinal manifestations and help to improve patient care.

BACKGROUND: We previously showed that abdominal distension in patients with functional gut disorders is due to a paradoxical diaphragmatic contraction without major increment in intraabdominal volume. Our aim was to characterize the pattern of gas retention and the abdomino-thoracic mechanics associated with abdominal distension in patients with intestinal dysmotility. METHODS: In 15 patients with manometrically proven intestinal dysmotility, two abdominal CT scans were performed: one during basal conditions and other during an episode of severe abdominal distension. In 15 gender- and age-matched healthy controls, a basal scan was performed. KEY RESULTS: In basal conditions, patients exhibited more abdominal gas than healthy subjects, particularly in the small bowel, and the volume significantly increased during an episode of distension. During episodes of abdominal distension, the increase in abdominal content was associated with increased girth and antero-posterior abdominal diameter, as well as a cephalic displacement of the diaphragm, which reduced the height of the lung. The consequent reduction in the air volume of the lung was attenuated by an increase in the antero-posterior diameter of the chest. CONCLUSIONS & INFERENCES: Abdominal distension in patients with severe intestinal dysfunction is related to marked pooling of gut contents, particularly in the small bowel. This increase in content is accommodated within the abdominal cavity by a global and coordinated abdomino-phreno-thoracic response, involving an accommodative ascent of the diaphragm and a compensatory expansion of the chest wall.

Fecal calprotectin and lactoferrin are sensitive markers of mucosal inflammation. We compared three different assays in their ability to identify patients with organic intestinal disease.In a post-hoc analysis of a prospective study, we examined 405 unselected patients with abdominal complaints referred for endoscopy to the University Hospital Basel, Switzerland. Calprotectin (EK-CAL, Bühlmann Laboratories, Switzerland; PhiCal, Calpro AS, Norway) and lactoferrin (IBD-Scan, Techlab, USA) were measured using enzyme-linked immunosorbent assays. The presence of a clinically significant endoscopic finding was the primary endpoint of the study. Final diagnoses were adjudicated blinded to calprotectin values.The prevalence of organic intestinal disease was 35.3%. Receiver operating characteristics analysis calculated an area under the curve (AUC) for EK-CAL of 0.918, which was significantly better than for PhiCal (AUC 0.842, P0.001) and IBD-Scan (AUC 0.830, P=0.003) to identify patients with organic intestinal disease. Overall test accuracy was 88.1% for EK-CAL, 83.7% for PhiCal, and 81.3% for IBD-Scan. Optimal cut-off value calculated for PhiCal and IBD-Scan were lower than recommended by the manufacturer.Monoclonal testing of calprotectin is superior to both polyclonal calprotectin testing and fecal lactoferrin in identifying symptomatic patients with organic intestinal disease.

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-Archiving Gut 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.

Background & Aims We examined the relationship between symptoms of depression and anxiety and clinical recurrence of inflammatory bowel disease (IBD) in a large patient cohort. We considered the progression of depression and anxiety over time. Methods We collected clinical and treatment data on 2007 adult participants of the Swiss IBD study (56% with Crohn's disease [CD], 48% male) performed in Switzerland from 2006 through 2015. Depression and anxiety symptoms were quantified by using the Hospital Anxiety and Depression Scale. The relationship between depression and anxiety scores and clinical recurrence was analyzed by using survival-time techniques. Results We found a significant association between symptoms of depression and clinical recurrence over time (for all patients with IBD, P = .000001; for subjects with CD, P = .0007; for subjects with ulcerative colitis, P = .005). There was also a significant relationship between symptoms of anxiety and clinical recurrence over time in all subjects with IBD ( P = .0014) and in subjects with CD ( P = .031) but not ulcerative colitis ( P = .066). Conclusions In an analysis of a large cohort of subjects with IBD, we found a significant association between symptoms of depression or anxiety and clinical recurrence. Patients with IBD should therefore be screened for clinically relevant levels of depression and anxiety and referred to psychologists or psychiatrists for further evaluation and treatment.

BurriE,HochholzerK,ArenjaN,Martin-Bras- chlerH,KaestnerL,GekelerH,HatziisaakT,Buttiker M, Fraulin A, Potocki M, Breidthardt T, Reichlin T, SocratesT,TwerenboldR,MuellerC (UniversityHos- pitalBasel,Basel;UniversityHospital,Basel,Switzer- land).B-typenatriureticpeptideintheevaluationand management of dyspnoea in primary care. J Intern Med 2012; 272:504-513. Objectives. The rapid and accurate diagnosis of heart failureinprimary careisamajorunmetclinicalneed. We evaluated the additional use of B-type natriuretic peptide(BNP)levels. Design.Arandomizedcontrolledtrial.

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.

Crohn’s disease and ulcerative colitis are characterized by periods of symptomatic relapse and remission. Diagnosis and assessment of inflammatory bowel disease has so far been based on clinical evaluation, serum parameters, radiology and endoscopy. Faecal markers such as calprotectin or lactoferrin have emerged as new diagnostic tools to detect and monitor intestinal inflammation. This review focuses on their potential clinical applications and limitations in the management of inflammatory bowel disease.

Measurement of faecal calprotectin concentration is increasingly used to assess disease activity in patients with IBD. Lasson et al. have now demonstrated that calprotectin concentrations in faeces of patients with mild or moderate left-sided or extensive ulcerative colitis vary considerably and have questioned the long-term stability of calprotectin when stored at room temperature.

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

Abdominal discomfort including pain, bloating and diarrhea is common. It often arises from functional gastrointestinal disorders but may indicate inflammatory bowel disease (IBD). Calprotectin is an abundant neutrophil protein that is released during inflammation. When measured in feces, it can be used to differentiate between non-organic and inflammatory intestinal disorders, especially to identify IBD. Fecal calprotectin might also be useful to monitor patients with IBD under treatment and to predict the risk of recurrence of active disease prior to clinical relapse. The use of fecal calprotectin has been investigated in a number of gastrointestinal disorders other than IBD, for example, as screening test for colorectal cancer but the available data are limited. This article summarizes the current literature on the use of fecal calprotectin in clinical practice.

European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE) criteria have been developed to increase diagnostic yield, but their predictive value is limited. We investigated the incremental diagnostic value of faecal calprotectin to EPAGE criteria.In a post-hoc analysis of a prospective study, EPAGE criteria were applied to 298 of 575 (51.8%) patients who had undergone esophagogastroduodenoscopy (EGD), colonoscopy or both for abdominal complaints at the Division of GastroenterologyHepatology at the University Hospital Basel in Switzerland. Faecal calprotectin was measured in stool samples collected within 24 hours before the investigation using an enzyme-linked immunosorbent assay. Final endoscopic diagnoses were blinded to calprotectin values.Of 149 EGDs and 224 colonoscopies, 17.6% and 14.7% respectively were judged inappropriate by EPAGE criteria. Appropriate or uncertain indications revealed more endoscopic findings in both EGD (46.3% vs. 23.1%, P = 0.049) and colonoscopy (23.6% vs. 6.1%, P = 0.041) than inappropriate indications. Median calprotectin levels were higher (81.5 μg/g, interquartile range 26-175, vs. 10 μg/g, IQR 10-22, P0.001) and testing was more often positive (50 μg/g) in patients with endoscopic findings, both in EGD (58.2% vs. 33.0%, P = 0.005) and in colonoscopy (57.3% vs. 7.4%, P0.001). The use of faecal calprotectin in addition to EPAGE criteria improved the risk reclassification of patients by endoscopic findings. The calculated net reclassification index was 37.8% (P = 0.002) for EGD and 110.9% (P0.001) for colonoscopy, thus improving diagnostic yield to 56.8% and 70.2%, respectively.The use of faecal calprotectin in addition to EPAGE criteria improved diagnostic yield in patients with abdominal complaints.

Background: Non-invasive monitoring of inflammatory bowel disease is an unmet clinical need as patients in clinical remission may have residual mucosal inflammation preceding clinical relapse. Aims: We aimed to assess the value of fecal calprotectin and standardized clinical activity scoring to monitor disease activity in ulcerative colitis under medical treatment. Methods: Forty-one patients with ulcerative colitis were included in a prospective observational study. Medical treatment was guided by clinical judgement of treating physicians. Fecal calprotectin and the clinical activity index (CAI) were measured blinded to treating physicians every 2months until the end of follow-up. Twenty-six patients received colonoscopy for clinical reason. Results: As defined by the CAI, patients were in clinical remission (63.4%), having mild (26.8%) or moderate (11.2%) disease activity. Of those in clinical remission (CAI≤4), 86.4% showed residual endoscopic activity (Mayo Score ≥1). Calprotectin levels were higher in endoscopically active disease (779.0 vs 331.5μg/g, P=0.034) and calprotectin testing identified more patients with endoscopic disease activity (86.4%) than the CAI (45.5%, P=0.034). Medical treatment was escalated in 90.2% during the study. Values of the CAI and calprotectin correlated with therapy escalation (OR 3.94 and 3.22, respectively). Only for calprotectin, changes between two measurements were related to intensified medical treatment (OR 1.39). Conclusion: Fecal calprotectin was similarly useful to the CAI to monitor disease activity of ulcerative colitis during medical treatment but identified endoscopic disease activity far more reliably. Changes of calprotectin values between measurements might indicate clinical relapse earlier than the CAI.

Patients with irritable bowel syndrome and abdominal bloating exhibit abnormal responses of the abdominal wall to colonic gas loads. We hypothesised that in patients with postprandial bloating, ingestion of a meal triggers comparable abdominal wall dyssynergia. Our aim was to characterise abdominal accommodation to a meal in patients with postprandial bloating.A test meal (0.8 kcal/ml nutrients plus 27 g/litre polyethylenglycol 4000) was administered at 50 ml/min as long as tolerated in 10 patients with postprandial bloating (fulfilling Rome III criteria for postprandial distress syndrome) and 12 healthy subjects, while electromyographic (EMG) responses of the anterior wall (upper and lower rectus, external and internal oblique via bipolar surface electrodes) and the diaphragm (via six ring electrodes over an oesophageal tube in the hiatus) were measured. Means +/- SD were calculated.Healthy subjects tolerated a meal volume of 913±308 ml; normal abdominal wall accommodation to the meal consisted of diaphragmatic relaxation (EMG activity decreased by 15±6%) and a compensatory contraction (25±9% increase) of the upper abdominal wall muscles (upper rectus and external oblique), with no changes in the lower anterior muscles (lower rectus and internal oblique). Patients tolerated lower volume loads (604±310 ml; p=0.030 vs healthy subjects) and developed a paradoxical response, that is, diaphragmatic contraction (14±3% EMG increment; p0.01 vs healthy subjects) and upper anterior wall relaxation (9±4% inhibition; p0.01 vs healthy subjects).In functional dyspepsia, postprandial abdominal distension is produced by an abnormal viscerosomatic response to meal ingestion that alters normal abdominal accommodation.

The monitoring of inflammatory bowel disease (IBD) based on clinical symptoms and activity scores alone has major drawbacks. Despite clinical remission, in many patients with ongoing low-grade inflammation and activity scores, there is a tendency to underestimate IBD activity as parameters depend on the subjective symptoms of the patients. C-reactive protein might identify patients with low-grade inflammation, especially in Crohn’s disease, but sensitivity remains limited. Recently, fecal markers of inflammation have been shown to correlate well with endoscopic disease activity and to predict relapse. However, data on serial measurements to guide therapy are scarce. The role of anti-TNF-α antibodies and plasma TNF-α concentrations in IBD therapy is currently unclear and needs to be defined further. The goal of improving disease outcome has not been demonstrated for any noninvasive biomarker so far.

Summary Inflammatory bowel disease (IBD) should be suspected in any patient presenting with chronic or recurrent abdominal pain and diarrhoea. Current guidelines suggest performing invasive endoscopy with histological sampling for further diagnosis. Measuring calprotectin, a neutrophilic protein, in faeces has been proposed as a surrogate marker of intestinal inflammation. Calprotectin values have been shown to reliably differentiate between IBD and non-organic disease in symptomatic patients and, when elevated, warrant early endoscopic investigation to rule out IBD and other organic pathologies. Endoscopy with histological sampling is also used to evaluate disease activity and here, too, faecal calprotectin values seem to correlate well. In a number of studies, faecal calprotectin values have consistently shown to better assess mucosal inflammation than clinical indices and serum markers. Calprotectin’s advantage of non-invasive monitoring of disease activity is especially beneficial when considering the dynamics of repeated measurements. Mucosal healing (MH) has been associated with sustained clinical remission, reduced rates of hospitalisation and of surgical resection, both in Crohn’s disease and ulcerative colitis patients. Elevated faecal calprotectin levels in patients in clinical remission are associated with increased risk of disease relapse within 12 months follow-up. In most clinically quiescent IBD, residual mucosal inflammation is still present; it appears that faecal calprotectin can detect subclinical mucosal inflammation and thus might identify patients at risk for relapse. In summary, measuring faecal calprotectin can be highly useful in the diagnosis and disease management of patients with IBD and could help predict disease course.

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: [NCT00130598][1] [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00130598&atom=%2Fehj%2Fearly%2F2012%2F01%2F19%2Feurheartj.ehr501.atom

Background 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. Methods 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. Results 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). Conclusion 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.

Liver-cell adenomas are benign lesions of the liver occurring predominantly in young women. Hepatocellular carcinomas in most of the cases arise in a cirrhotic liver during the fifth or sixth decade. We describe the case of a 40-year-old woman in whom work-up for epigastric pain revealed a peptic ulcer and a large hepatic mass. Tests for chronic liver diseases were negative. Imaging findings and biopsy specimens of the tumour were inconclusive. The tumour was surgically removed and a hepatocellular carcinoma arising within a liver-cell adenoma in a non-cirrhotic liver was found. Malignant transformation of liver-cell adenoma has only been reported in a few case reports. Mechanisms of transformation remain unclear. The imaging findings as well as histological features are presented in detail and the literature is discussed.

AIM: To evaluate the diagnostic capability of calprotectin in ascitic fluid for detecting a polymorphonuclear (PMN) cell count > 250/μL ascites. METHODS: In this prospective observational study, a total of 130 ascites samples were analysed from 71 consecutive patients referred for paracentesis. Total and differential leukocyte cell counts were determined manually with a Neubauer chamber and gentian-violet stain. Calprotectin was measured in 1 mL ascetic fluid by enzyme-linked immunosorbent assay (ELISA) and a point-of-care (POC) lateral flow assay with the Quantum Blue® Reader (Buhlmann Laboratories). All measurements were carried out in a central laboratory by senior personnel blinded to patient history. A PMN count > 250/μL was the primary endpoint of the study. The diagnostic value of ascitic calprotectin measurement was assessed by comparing to the final diagnosis of each patient that had been adjudicated by investigators blinded to calprotectin values. RESULTS: The PMN count was > 250/μL in 19 samples (14.6%) from 15 patients (21.1%) and varied widely among the study population (range 10-19 800/mL and 1-17 820/mL, respectively). Spontaneous bacterial peritonitis (SBP) was the final diagnosis in four patients (5.6%). All patients with PMN ≤ 250/μL had negative bacterial culture. PMN count was elevated in five patients with peritoneal carcinomatosis, three with lymphoma, one with neuroendocrine carcinoma, and two with secondary peritonitis due to abdominal perforation. PMN cell counts correlated with ascitic calprotectin values (Spearman’s rho; r = 0.457 for ELISA, r = 0.473 for POC). A considerable range of ascitic calprotectin concentrations was detected by ELISA [median 0.43 μg/mL, interquartile range (IQR) 0.23-1.23 (range 0.10-14.93)] and POC [median 0.38 μg/mL, IQR 0.38-0.56 (range 0.38-13.31)]. Ascitic calprotectin levels were higher in samples with PMN > 250/μL, by both ELISA [median (IQR) 2.48 μg/mL (1.61-3.65) vs 0.10 μg/mL (0.10-0.36), P < 0.001] and POC [2.78 μg/mL (2.05-5.37) vs 0.38 μg/mL (0.38-0.41), P < 0.001]. The area under the receiver operating characteristics curve for identifying an elevated PMN count was 0.977 (95%CI: 0.933 to 0.995) for ELISA and 0.982 (95%CI: 0.942 to 0.997) for POC (P = 0.246 vs ELISA). Using the optimal cut-off value for ELISA (0.63 μg/mL), ascitic calprotectin had 94.8% sensitivity, 89.2% specificity, positive and negative likelihood ratios of 8.76 and 0.06 respectively, positive and negative predictive values of 60.0% and 99.0% respectively, and 90.0% overall accuracy. Using the optimal cut-off value for POC (0.51 μg/mL), the respective values were 100.0%, 84.7%, 6.53, 0.00, 52.8%, 100% and 87.7%. Correlation between ELISA and POC was excellent (r = 0.873, P < 0.001). The mean ± SD of the difference was -0.11 ± 0.48 μg/mL with limits of agreement of + 0.8 μg/mL (95%CI: 0.69 to 0.98) and -1.1 μg/mL (95%CI: -1.19 to -0.91). CONCLUSION: Ascitic calprotectin reliably predicts PMN count > 250/μL, which may prove useful in the diagnosis of SBP, especially with a readily available bedside testing device.

The diagnostic and prognostic value of arterial blood gas analysis (ABGA) parameters in unselected patients presenting with acute dyspnea to the Emergency Department (ED) is largely unknown. We performed a post-hoc analysis of two different prospective studies to investigate the diagnostic and prognostic value of ABGA parameters in patients presenting to the ED with acute dyspnea. We enrolled 530 patients (median age 74 years). ABGA parameters were neither useful to distinguish between patients with pulmonary disorders and other causes of dyspnea nor to identify specific disorders responsible for dyspnea. Only in patients with hyperventilation from anxiety disorder, the diagnostic accuracy of pH and hypoxemia rendered valuable with an area under the receiver operating characteristics curve (AUC) of 0.86. Patients in the lowest pH tertile more often required admission to intensive care unit (28% vs 12% in the first tertile, P < 0.001) and had higher in-hospital (14% vs 5%, P = 0.003) and 30-day mortality (17% vs 7%, P = 0.002). Cumulative mortality rate was higher in the first (37%), than in the second (28%), and the third tertile (23%, P = 0.005) during 12 months follow-up. pH at presentation was an independent predictor of 12-month mortality in multivariable Cox proportional hazard analysis both for patients with pulmonary (P = 0.043) and non-pulmonary disorders (P = 0.038). ABGA parameters provide limited diagnostic value in patients with acute dyspnea, but pH is an independent predictor of 12 months mortality.