Lucas Wauters

Reproducibility and Agreement of Pharyngeal Automated Impedance Manometry With Videofluoroscopy

BACKGROUND & AIMS Automated impedance manometry analysis (AIM) measures swallow function variables that define bolus timing, intrabolus pressure, contractile vigor, and bolus presence; these are combined to derive a swallow risk index (SRI) that is correlated with pharyngeal dysfunction and aspiration. We assessed intra-rater and inter-rater reproducibility of AIM analysis-derived variables; the diagnostic accuracy of AIM-based criteria for detecting aspiration was determined by using expertly scored videofluoroscopy as the standard. METHODS Data on 50 bolus swallows of 10 mL each were randomly selected from a database of swallows that were simultaneously recorded with impedance, manometry, and videofluoroscopy. Data were divided into 5 subgroups of 10 swallows for analysis: 10 dysphagic liquid, 10 dysphagic liquid with aspiration, 10 dysphagic semisolid, 10 control liquid, and 10 control semisolid. Repeat analyses were performed by 10 observers with varying levels of expertise in manometry by using purpose-designed software (AIMplot). Swallow videos were scored by 4 experts by using the penetration-aspiration scale (PAS) score. Reproducibility of calculation of swallow function variables and the SRI and PAS was assessed by using intraclass correlation coefficient (ICC). The majority consensus of expert PAS scores was used to dichotomously define aspiration (consensus PAS >3). Observer analyses were compared by Cohen κ statistical analysis. RESULTS The intra-rater and inter-rater reproducibility of swallow function variables was high (SRI mean intra-rater ICC, 0.97 and mean inter-rater ICC, 0.91). SRI >15-20 was optimal for detecting the presence of aspiration during liquid bolus swallows with an almost perfect agreement with expert scoring of videofluoroscopy (κ > 0.8). CONCLUSIONS AIM analysis has high intra-rater and inter-rater reproducibility, and among observers of varying expertise, SRI predicts the presence of aspiration.

Oesophageal pressure-flow metrics in relation to bolus volume, bolus consistency, and bolus perception

Background The utility of combined oesophageal pressure–impedance recording has been enhanced by automation of data analysis. Objective To understand how oesophageal function as measured by automated impedance manometry (AIM) pressure-flow analysis varies with bolus characteristics and subjective perception of bolus passage. Methods Oesophageal pressure–impedance recordings of 5 and 10 ml liquid or viscous swallows and 2 and 4 cm solid swallows from 20 healthy control subjects (five male; 25–73 years) were analysed. Metrics indicative of bolus pressurization (intrabolus pressure and intrabolus pressure slope) were derived. Bolus flow resistance, the relationship between bolus pressurization and flow timing, was assessed using a pressure-flow index. Bolus retention was assessed using the ratio of nadir impedance to peak pressure impedance (impedance ratio). Subjective perception of bolus passage was assessed swallow by swallow. Results Viscosity increased the bolus flow resistance and reduced bolus clearance. Responses to boluses of larger volume and more viscous consistency revealed a positive correlation between bolus pressurization and oesophageal peak pressure. Flow resistance was higher in subjects who perceived bolus hold up of solids. Conclusions Bolus volume and bolus type alter oesophageal function and impact AIM analysis metrics descriptive of oesophageal function. Perception of bolus transit was associated with heightened bolus pressurization relative to bolus flow.

Functional dyspepsia is associated with duodenal eosinophilia in an Australian paediatric cohort

The pathophysiology of functional dyspepsia (FD) remains unknown. Duodenal eosinophil infiltration has been reported.

Cow's Milk Allergy Prescribing Is Influenced by Regional and National Guidance.

Objectives: Cows milk allergy (CMA) is the most common food allergy in children with many clinical manifestations, leading to misdiagnoses such as gastro-oesophageal reflux, infantile colic, and lactose intolerance with inappropriate prescribing. We aimed to determine the impact of infant feeding guidelines on CMA prescribing in UK primary care using a simple and inexpensive training package. Methods: Prospectively collected data of infant feeding prescriptions in Northern Ireland from June 2012 to March 2014 were analysed with the intervention period between November 2012 and March 2013. A comparison was made between hypoallergenic formulae, appropriate for CMA, versus alternative prescriptions including antiregurgitation and colic products, lactose-free and partially hydrolysed milks, or infant Gaviscon. Results: Comparing pre- and postintervention period, the total quantity of hypoallergenic formulae increased by 63.2% and alternative prescriptions decreased by 44.6% (P < 0.001). The total amount of all prescribed products decreased by 41.0% (P < 0.001). During the study period, the proportion of recommended CMA treatment increased from 3.4% before training to 9.8% in the short- and long-term follow-up (P < 0.001). The overall increase was £33,508 per year or £95.5 per general practitioners surgery. Conclusions: We present the first study evaluating the impact of infant feeding guidelines on CMA prescribing in UK primary care. Practical advice and teaching of health professionals allowed for effective implementation of regional and national guidelines, with a significant impact on prescription patterns. This study shows promising results for prospective research on a national scale, including socioeconomical impact and cost-effectiveness.

Long-term Outcomes with Anti-TNF Therapy and Accelerated Step-up in the Prospective Pediatric Belgian Crohn's Disease Registry (BELCRO)

Background: Accelerated step-up or anti–tumor necrosis factor (TNF) before first remission is currently not recommended in pediatric Crohns disease. Methods: Five-year follow-up data from a prospective observational cohort of children diagnosed with Crohns disease in Belgium were analyzed. Disease severity was scored as inactive, mild, or moderate to severe. Remission or inactive disease was defined as sustained if lasting ≥2 years. Univariate analyses were performed between anti-TNF–exposed versus naive patients and anti-TNF before versus after first remission and correlations assessed with primary outcomes average disease severity and sustained remission. Results: A total of 91 patients (median [IQR] age 12.7 [10.9–14.8] yrs, 53% male) were included. Disease location was 12% L1, 23% L2, and 64% L3 with 76% upper gastrointestinal and 30% perianal involvement. Disease severity was 25% mild and 75% moderate to severe. Of 66 (73%) anti-TNF–exposed patients, 34 (52%) had accelerated step-up. Anti-TNF use was associated with age (13.1 [11.5–15.2] versus 11.8 [8.7–13.8] yrs; P < 0.05), L2 (29% versus 8%; P = 0.04), and average disease severity (1.7 [1.4–1.9] versus 1.4 [1.3–1.6]; P < 0.001). Duration of anti-TNF correlated with average disease severity (r = 0.32, P = 0.002). Accelerated step-up was also associated with age (13.3 [12.1–15.9] versus 12.5 [10.2–14.1]; P = 0.02) and average disease severity (1.8 [1.6–1.9] versus 1.6 [1.3–1.8]; P = 0.002). Duration of sustained remission was similar in all patients, and no serious infections, cancer, or deaths were reported. Conclusions: Anti-TNF therapy and accelerated step-up in older patients with more severe disease leads to beneficial long-term outcomes.

Incidence of renal cell carcinoma in inflammatory bowel disease patients with and without anti-TNF treatment.

Objective We aimed to study the risk of renal cell carcinoma (RCC) with anti-tumor necrosis factor (anti-TNF) therapy in inflammatory bowel disease (IBD) and rheumatic diseases (RD) and calculate standardized incidence ratios (SIRs) in IBD. Materials and methods This was a retrospective case–control and cohort study spanning 25 years, including IBD and RD patients with a diagnosis of RCC (1990–2014) identified through the electronic database of a tertiary referral center. Results RCC was confirmed in seven anti-TNF-exposed (TNF+) and 21 anti-TNF-naive (TNF−) IBD and one TNF+ and 26 TNF− RD patients. In IBD-RCC, younger age at RCC diagnosis [median (interquartile range) 46 (42–58) vs. 63 (52–75) years; P=0.02], immunosuppressive therapy (100 vs. 24%; P<0.0004), partial nephrectomy (86 vs. 33%; P=0.02), and surgery less than 1 month after diagnosis of RCC (71 vs. 14%; P=0.004) were associated with anti-TNF. Compared with IBD, RD patients were older at RCC diagnosis [70 (60–77) vs. 59 (47–69) years; P=0.02] with less nephron-sparing surgery (26 vs. 54%; P=0.04) and more symptomatic (44 vs. 14%; P=0.02) and advanced tumors (30 vs. 7%; P=0.04). SIRs in IBD-RCC TNF− and TNF+ were 5.4 (95% confidence interval 2.9–9.2) and 7.1 (2.3–16.5) in male patients and 8.5 (3.7–16.8) and 4.8 (0.6–17.3) in female patients, respectively. The risk for RCC associated with anti-TNF in IBD was 0.8 (0.3–2.5) in men and 1.4 (0.2–5.5) in women. Conclusion The favorable patient and tumor profiles in IBD with anti-TNF may suggest incidentally discovered RCC on abdominal imaging. SIRs for IBD-RCC were not increased after anti-TNF exposure.

OP-23 FUNCTIONAL DYSPEPSIA IS ASSOCIATED WITH DUODENAL EOSINOPHILIA IN A PEDIATRIC COHORT.

Objectives: Functional dyspepsia (FD) is a highly prevalent gastrointestinal disorder with unknown etiology. We aimed to assess the association between dyspeptic symptoms and duodenal eosinophilia in children referred for upper endoscopy. Methods: In this retrospective cohort study, all histopathology reports of normal upper endoscopies performed at a single tertiary center between 2010 and 2014 were reviewed. FD was defined as epigastric pain or discomfort for more than 2 months with no response to acid suppressants. Controls were those with non-erosive reflux disease, dysphagia or rumination syndrome. Duodenal biopsies were analyzed by pathologists blinded to indication. Intramucosal eosinophils were counted per mm2 on haematoxylin and eosin stained digital imaged sections using Aperio eSlide Manager. Demographics, clinical variables, family history and histologic findings were compared between cases and controls. Results: In total, 36 cases and 36 non-matched controls were identified of which 56% and 53% were female (p = 0.81). Mean (± SD) age was higher in cases compared to controls (13.6 (± 3.1) vs. 10.5 (± 4.0) years; p = .001). Dyspeptic symptoms (epigastric pain 81% and/or upper abdominal discomfort 33%) were food-related in 69% and nocturnal in 31% of cases. Self-reported nausea (64% vs. 17%; p < .0001), lethargy (19% vs. 0%; p = .005) and a family history of functional gastrointestinal disorders (28% vs. 3%; p = .003) were more common in cases than controls. There was a higher but not significantly different rate of atopic history (39% vs. 25%; p = .21) and psychological co-morbidity (53% vs. 39%; p = .24) in FD cases versus controls. Duodenal intraepithelial lymphocytes per 100 enterocytes were similar in cases and controls (median (IQR) 10 (8–13) vs. 12 (8–18); p = 0.12). Duodenal eosinophil counts per mm2 were significantly increased in cases compared to controls (151 (118–207) vs. 76 (60–106); p < 0.001). Conclusions: This study confirms recent reports of duodenal eosinophilia in FD. The high rate of atopic and psychological co-morbidity in FD suggests multi-factorial mechanisms and may explain why current therapeutic options aimed at symptom control are largely unsatisfactory. Duodenal eosinophilia in FD should be considered a therapeutic target.

Applications of peptide hormone ligands for the treatment of dumping and short bowel syndrome

HighlightsPasireotide, a novel somatostatin analogue, is effective in early and late dumping syndrome.GLP‐1 analogues alleviate signs and symptoms of dumping syndrome.Teduglutide decreases the needs for parenteral support in short bowel syndrome.The effects of GLP‐1 analogues in short bowel syndrome are promising. &NA; Dumping syndrome is a common and debilitating complication of upper gastrointestinal surgery. Accelerated gastric emptying and dysregulated secretion of gastrointestinal (GI) hormones are involved in its pathophysiology. Pasireotide, a novel somatostatin analogue, improved dumping in a phase‐2 study. Preliminary data suggest that the glucagon‐like peptide‐1 (GLP‐1) analogue liraglutide can also improve dumping. Short bowel syndrome is the most common cause of intestinal failure and involves not only a loss of mucosal absorptive area but also hypersecretion and accelerated transit. GLP‐2 is the best studied hormone involved in intestinal adaptation. An increasing body of evidence demonstrates that the GLP‐2 analogue teduglutide reduces parenteral support needs. New GLP‐2 analogues and analogues of other GI hormones such as liraglutide are being investigated as promising treatments in short bowel syndrome.

Infective Esophagitis: Inhaled Steroids Treatment for Eosinophilic Esophagitis not Always Safe

A 23-year-old male presented with acute dysphagia and odynophagia for solids. He had multiple episodes of vomiting, retrosternal chest pain and fever but denied shortness of breath of cough. He was previously diagnosed with EoE aged 16 years following presentation with an acute food bolus obstruction, on a background of long standing dysphagia. His other medical history was unremarkable, with no history of allergies or atopy. He had no known history of HSV infection. Following the initial diagnosis, he was treated with inhaled Fluticasone 250mcg 2 puffs twice a day swallowed and Omeprazole 20mg daily with symptomatic relief. The repeat esophagogastroscopy (EGD) showed some persistent ridging and edema. Biopsy showed showed persistent features of EoE with raised eosinophil counts. Overall, he had symptomatic improvement but EoE remained resistant to standard treatment endoscopically and histologically.

Letter: functional dyspepsia is associated with duodenal eosinophilia in an Australian paediatric cohort—methodological issues to avoid misinterpretation. Authors’ reply

SIRS, We read with interest the comments on the statistical methods that we used in our paper. As we stated, our study aimed to assess a hypothesised relationship between duodenal eosinophilia and functional dyspepsia, rather than to determine predictors of functional dyspepsia, as suggested in the letter from Drs. Safiri and Ayubi. The distinction is important, as we were primarily interested in the association between duodenal eosinophilia and functional dyspepsia case status. This association remains statistically significant even when exact, rather than asymptotic, statistical inference is used both on univariate (OR = 28.8; 95% CI: 7.4-139.2) and multivariate analysis (OR = 26.4; 95% CI: 5.6-183.2). Other variables in our model are only included to control for potential confounders of this relationship. Despite this, we believe that the best validation of the findings is replication in an independent sample, rather than reanalysing our data using different statistical methods. We acknowledge that there is reduced power to identify confounders in this analysis given the relatively small sample size. However, we do not agree that this translates to a bias.