An expert panel-based study on recognition of gastro-esophageal reflux in difficult esophageal pH-impedance tracings.

BACKGROUND: Despite existing criteria for scoring gastro-esophageal reflux (GER) in esophageal multichannel pH-impedance measurement (pH-I) tracings, inter- and intra-rater variability is large and agreement with automated analysis is poor. To identify parameters of difficult to analyze pH-I patterns and combine these into a statistical model that can identify GER episodes with an international consensus as gold standard. METHODS: Twenty-one experts from 10 countries were asked to mark GER presence for adult and pediatric pH-I patterns in an online pre-assessment. During a consensus meeting, experts voted on patterns not reaching majority consensus (>70% agreement). Agreement was calculated between raters, between consensus and individual raters, and between consensus and software generated automated analysis. With eight selected parameters, multiple logistic regression analysis was performed to describe an algorithm sensitive and specific for detection of GER. KEY RESULTS: Majority consensus was reached for 35/79 episodes in the online pre-assessment (interrater κ = 0.332). Mean agreement between pre-assessment scores and final consensus was moderate (κ = 0.466). Combining eight pH-I parameters did not result in a statistically significant model able to identify presence of GER. Recognizing a pattern as retrograde is the best indicator of GER, with 100% sensitivity and 81% specificity with expert consensus as gold standard. CONCLUSIONS & INFERENCES: Agreement between experts scoring difficult impedance patterns for presence or absence of GER is poor. Combining several characteristics into a statistical model did not improve diagnostic accuracy. Only the parameter 'retrograde propagation pattern' is an indicator of GER in difficult pH-I patterns.

New insights in gastroesophageal reflux, esophageal function and gastric emptying in relation to dysphagia before and after anti-reflux surgery in children.

In children with gastroesophageal reflux (GER) disease refractory to pharmacological therapies, anti-reflux surgery (fundoplication) may be a treatment of last resort. The applicability of fundoplication has been hampered by the inability to predict which patient may benefit from surgery and which patient is likely to develop post-operative dysphagia. pH impedance measurement and conventional manometry are unable to predict dysphagia, while the role of gastric emptying remains poorly understood. Recent data suggest that the selection of patients who will benefit from surgery might be enhanced by automated impedance manometry pressure-flow analysis (AIM) analysis, which relates bolus movement and pressure generation within the esophageal lumen.

Esophageal impedance baselines in infants before and after placebo and proton pump inhibitor therapy.

BACKGROUND: Esophageal impedance monitoring records changes in conductivity. During esophageal rest, impedance baseline values may represent mucosal integrity. The aim of this study was to assess the influence of acid suppression on impedance baselines in a placebo-controlled setting. METHODS: Impedance recordings from 40 infants (0-6 months) enrolled in randomized placebo-controlled trials of proton pump inhibitor (PPI) were retrospectively analyzed. Infants underwent 24 h pH-impedance monitoring prior to and after 2 weeks of double blind therapy with placebo or a PPI. Typical clinical signs of gastro-esophageal reflux (GER) were recorded and I-GERQ-R questionnaire was completed. KEY RESULTS: Median (IQR) impedance baseline increased on PPI treatment (from 1217 (826-1514) to 1903 (1560-2194) Ω, P < 0.001) but not with placebo (from 1445 (1033-1791) to 1650 (1292-1983) Ω, P = 0.13). Baselines before treatment inversely correlate with the number of GER, acid GER, weakly acid GER, acid exposure, and symptoms. The change in baseline on treatment inversely correlates with acid exposure and acid GER. Patients with initial low baselines have no improved symptomatic response to treatment. CONCLUSIONS & INFERENCES: Impedance baselines are influenced by GER and increase significantly more with PPI therapy than with placebo. Clinical impact of this observation remains undefined as targeting therapy at infants with low baselines does not improve symptomatic response to treatment.

Gastroesophageal reflux in pediatrics; (patho)physiology and new insights in diagnostics and treatment.

GER is the passage of gastric contents into the esophagus and is referred to as GER disease (GERD) when GER causes troublesome symptoms and/or complications. GERD in infants and children is sometimes difficult to diagnose and even more difficult to treat. The diagnosis of GERD is hampered by the fact that GER symptoms such as irritability and crying, feed refusal and regurgitation are common problems in infants and these symptoms are not specific for GERD. Diagnostic criteria for the objective diagnosis of GERD with commonly used diagnostic tests such as pH-metry, pH-impedance monitoring and endoscopy are poorly or not defined. In this review the current understanding of (patho)physiology of GERD, clinical history in infants and children, new insights in diagnostic modalities and the role of non-pharmacological and pharmacological interventions are discussed.

Decreased active von Willebrand factor level owing to shear stress in aortic stenosis patients.

BACKGROUND: Aortic stenosis patients often show bleeding complications. Previously, a prolonged platelet function analyzer (PFA-100) closure time was observed with plasma of severe aortic stenosis patients. To elucidate a possible role of circulating preactivated von Willebrand factor (VWF), we determined the level of VWF in its active, platelet-binding conformation in plasma of patients with aortic stenosis. PATIENTS/METHODS: Sixty-two aortic stenosis patients were included in this study. VWF and related parameters were measured, and the results were related to severity of aortic stenosis. RESULTS: VWF activation factor, indicating the proportion of circulating VWF able to bind to platelets, correlated negatively with peak transvalvular gradient and PFA-100 closure time. No correlation was observed between ADAMTS13 activity and peak transvalvular gradient or PFA-100 closure time. Both VWF antigen and VWF propeptide levels were significantly higher in patients with mild and moderate aortic stenosis, but not in those with severe stenosis. CONCLUSIONS: Our data demonstrate that the aortic pressure gradient is inversely associated with VWF activation factor, but not with VWF antigen or VWF multimerization in patients with aortic stenosis. These findings might have implications for the bleeding observed in patients with aortic stenosis.