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

This item is under embargo for a period of 12 months from the date of publication, in accordance with the publisher's policy.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

Author version made available in accordance with the publisher's policy.ABSTRACT 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. Material and Methods Impedance recordings from 40 infants (0-6months) enrolled in randomized placebo controlled trials of proton pump inhibitor (PPI) were retrospectively analyzed. Infants underwent 24hr pH-impedance monitoring prior to and after two weeks of double blind therapy with placebo or a PPI. Typical clinical signs of gastroesophageal 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) Ohm, p<0.001) but not with placebo (from 1445 (1033-1791) to 1650 (1292-1983) Ohm, 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 and 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

The influence of motion artefacts on magnetic resonance imaging of the clavicles for age estimation

Purpose To determine how motion affects stage allocation to the clavicle's sternal end on MRI. Materials and methods Eighteen volunteers (9 females, 9 males) between 14 and 30 years old were prospectively scanned with 3-T MRI. One resting-state scan was followed by five intentional motion scans. Additionally, a control group of 72 resting-state scans were selected from previous research. Firstly, six observers allocated developmental stages to the clavicles independently. Secondly, they re-assessed the images, allocating developmental statuses (immature, mature). Finally, the resting-state scans of the 18 volunteers were assessed in consensus to decide on the "correct" stage/status. Results were compared between groups (control, prospective resting state, prospective motion), and between staging techniques (stages/statuses). Results Inter-observer agreement was low (Krippendorff alpha 0.23-0.67). The proportion of correctly allocated stages (64%) was lower than correctly allocated statuses (83%). Overall, intentional motion resulted in fewer assessable images and less images of sufficient evidential value. The proportion of correctly allocated stages did not differ between resting-state (64%) and motion scans (65%), while correctly allocated statuses were more prevalent in resting-state scans (83% versus 77%). Remarkably, motion scans did not render a systematically higher or lower stage/status, compared to the consensus. Conclusion Intentional motion impedes clavicle MRI for age estimation. Still, in case of obvious disturbances, the forensic expert will consider the MRI unsuitable as evidence. Thus, the development of the clavicle as such and the staging technique seem to play a more important role in allocating a faulty stage for age estimation

Staging clavicular development on MRI : pitfalls and suggestions for age estimation

Background MRI of the clavicle's sternal end has been studied for age estimation. Several pitfalls have been noted, but how they affect age estimation performance remains unclear. Purpose/Hypothesis To further study these pitfalls and to make suggestions for a proper use of clavicle MRI for forensic age estimation. Our hypotheses were that age estimation would benefit from 1) discarding stages 1 and 4/5; 2) including advanced substages 3aa, 3ab, and 3ac; 3) taking both clavicles into account; and 4) excluding morphological variants. Study Type Prospective cross-sectional. Population Healthy Caucasian volunteers between 11 and 30 years old (524; 277 females, 247 males). Field Strength/Sequence 3T, T-1-weighted gradient echo volumetric interpolated breath-hold examination (VIBE) MR-sequence. Assessment Four observers applied the most elaborate staging technique for long bone development that has been described in the current literature (including stages, substages, and advanced substages). One of the observers repeated a random selection of the assessments in 110 participants after a 2-week interval. Furthermore, all observers documented morphological variants. Statistical Tests Weighted kappa quantified reproducibility of staging. Bayes' rule was applied for age estimation with a continuation ratio model for the distribution of the stages. According to the hypotheses, different models were tested. Mean absolute error (MAE) differences between models were compared, as were MAEs between cases with and without morphological variants. Results Weighted kappa equaled 0.82 for intraobserver and ranged between 0.60 and 0.64 for interobserver agreement. Stages 1 and 4/5 were allocated interchangeably in 4.3% (54/1258). Age increased steadily in advanced substages of stage 3, but improvement in age estimation was not significant (right P = 0.596; left P = 0.313). The model that included both clavicles and discarded stages 1 and 4/5 yielded an MAE of 1.97 years, a root mean squared error of 2.60 years, and 69% correctly classified minors. Morphological variants rendered significantly higher MAEs (right 3.84 years, P = 0.015; left 2.93 years, P = 0.022). Data Conclusion Our results confirmed hypotheses 3) and 4), while hypotheses 1) and 2) remain to be investigated in larger studies. Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019

Complex Odor from Plants under Attack: Herbivore's Enemies React to the Whole, Not Its Parts

Background: Insect herbivory induces plant odors that attract herbivores ’ natural enemies. Assuming this attraction emerges from individual compounds, genetic control over odor emission of crops may provide a rationale for manipulating the distribution of predators used for pest control. However, studies on odor perception in vertebrates and invertebrates suggest that olfactory information processing of mixtures results in odor percepts that are a synthetic whole and not a set of components that could function as recognizable individual attractants. Here, we ask if predators respond to herbivoreinduced attractants in odor mixtures or to odor mixture as a whole. Methodology/Principal Findings: We studied a system consisting of Lima bean, the herbivorous mite Tetranychus urticae and the predatory mite Phytoseiulus persimilis. We found that four herbivore-induced bean volatiles are not attractive in pure form while a fifth, methyl salicylate (MeSA), is. Several reduced mixtures deficient in one component compared to the full spider-mite induced blend were not attractive despite the presence of MeSA indicating that the predators cannot detect this component in these odor mixtures. A mixture of all five HIPV is most attractive, when offered together with the noninduced odor of Lima bean. Odors that elicit no response in their pure form were essential components of the attractive mixture. Conclusions/Significance: We conclude that the predatory mites perceive odors as a synthetic whole and that th

Pressure-Flow Characteristics of Normal and Disordered Esophageal Motor Patterns

Copyright © 2015 Elsevier Inc. All rights reserved This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Objective To perform pressure-flow analysis (PFA) in a cohort of pediatric patients who were referred for diagnostic manometric investigation. Study design PFA was performed using purpose designed Matlab-based software. The pressure-flow index (PFI), a composite measure of bolus pressurization relative to flow and the impedance ratio, a measure of the extent of bolus clearance failure were calculated. Results Tracings of 76 pediatric patients (32 males; 9.1 ± 0.7 years) and 25 healthy adult controls (7 males; 36.1 ± 2.2 years) were analyzed. Patients mostly had normal motility (50%) or a category 4 disorder and usually weak peristalsis (31.5%) according to the Chicago Classification. PFA of healthy controls defined reference ranges for PFI ≤142 and impedance ratio ≤0.49. Pediatric patients with pressure-flow (PF) characteristics within these limits had normal motility (62%), most patients with PF characteristics outside these limits also had an abnormal Chicago Classification (61%). Patients with high PFI and disordered motor patterns all had esophagogastric junction outflow obstruction. Conclusions Disordered PF characteristics are associated with disordered esophageal motor patterns. By defining the degree of over-pressurization and/or extent of clearance failure, PFA may be a useful adjunct to esophageal pressure topography-based classification

Novel pressure-impedance parameters for evaluating esophageal function in pediatric achalasia

Objective: In achalasia, absent peristalsis and reduced esophagogastric junction (EGJ) relaxation and compliance underlie dysphagia symptoms. Novel high-resolution impedance manometry variables, that is, bolus presence time (BPT) and trans-EGJ-bolus flow time (BFT) have been developed to estimate the duration of EGJ opening and trans-EGJ bolus flow. The aim of this study was to evaluate esophageal motor function and bolus flow in children diagnosed with achalasia using these variables. Methods: High-resolution impedance manometry recordings from 20 children who fulfilled the Chicago Classification (V3) criteria for achalasia were compared with recordings of 15 children with normal esophageal high-resolution manometry findings and no other evidence suggestive of achalasia. Matlab-based analysis software was used to calculate BPT and BFT. Results: Both BPT and BFT were significantly reduced in achalasia patients compared with children with normal esophageal motility (BPT 3.3 s vs 5.1 s P < 0.01; BFT 1.4 s vs 4.3 s P < 0.001). BFT was significantly lower than BPT (achalasia difference 1.9 s ± 1.3 s, P = 0.001 and normal difference 0.9 ± 0.3 s, P = 0.001). Overall, there was a significant correlation between BPT and BFT (r = 0.825, P < 0.001). We observed a 2-way differentiation of achalasia patients; those in whom the BPT and BFT were proportional, but significantly lower than in patients with normal peristalsis, and those in whom BFT was disproportionately lower than BPT. Conclusions: Calculation of BPT and BFT may help determine whether esophageal bolus transport to the EGJ and/or esophageal emptying through the EGJ are aberrant. For achalasia, this may detect flow resistance at the EGJ, potentially improving both diagnosis and objective assessment of therapeutic effects

Intra- and interrater reliability of the Chicago Classification of achalasia subtypes in pediatric High Resolution Esophageal Manometry (HRM) recordings

This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving'. © 2017 John Wiley & Sons, Inc. All rights reserved. This author accepted manuscript is made available following 12 month embargo from date of publication (June 2017) in accordance with the publisher’s archiving policyBackground Subtyping achalasia by high‐resolution manometry (HRM) is clinically relevant as response to therapy and prognosis have shown to vary accordingly. The aim of this study was to assess inter‐ and intrarater reliability of diagnosing achalasia and achalasia subtyping in children using the Chicago Classification (CC) V3.0. Methods Six observers analyzed 40 pediatric HRM recordings (22 achalasia and 18 non‐achalasia) twice by using dedicated analysis software (ManoView 3.0, Given Imaging, Los Angeles, CA, USA). Integrated relaxation pressure (IRP4s), distal contractile integral (DCI), intrabolus pressurization pattern (IBP), and distal latency (DL) were extracted and analyzed hierarchically. Cohen's κ (2 raters) and Fleiss’ κ (>2 raters) and the intraclass correlation coefficient (ICC) were used for categorical and ordinal data, respectively. Results Based on the results of dedicated analysis software only, intra‐ and interrater reliability was excellent and moderate (κ=0.89 and κ=0.52, respectively) for differentiating achalasia from non‐achalasia. For subtyping achalasia, reliability decreased to substantial and fair (κ=0.72 and κ=0.28, respectively). When observers were allowed to change the software‐driven diagnosis according to their own interpretation of the manometric patterns, intra‐ and interrater reliability increased for diagnosing achalasia (κ=0.98 and κ=0.92, respectively) and for subtyping achalasia (κ=0.79 and κ=0.58, respectively). Conclusions Intra‐ and interrater agreement for diagnosing achalasia when using HRM and the CC was very good to excellent when results of automated analysis software were interpreted by experienced observers. More variability was seen when relying solely on the software‐driven diagnosis and for subtyping achalasia. Therefore, diagnosing and subtyping achalasia should be performed in pediatric motility centers with significant expertise

Long-term follow-up including extensive complement analysis of a pediatric C3 glomerulopathy cohort

BACKGROUND: C3 glomerulopathy (C3G) is a rare kidney disorder characterized by predominant glomerular depositions of complement C3. C3G can be subdivided into dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). This study describes the long-term follow-up with extensive complement analysis of 29 Dutch children with C3G. METHODS: Twenty-nine C3G patients (19 DDD, 10 C3GN) diagnosed between 1992 and 2014 were included. Clinical and laboratory findings were collected at presentation and during follow-up. Specialized assays were used to detect rare variants in complement genes and measure complement-directed autoantibodies and biomarkers in blood. RESULTS: DDD patients presented with lower estimated glomerular filtration rate (eGFR). C3 nephritic factors (C3NeFs) were detected in 20 patients and remained detectable over time despite immunosuppressive treatment. At presentation, low serum C3 levels were detected in 84% of all patients. During follow-up, in about 50% of patients, all of them C3NeF-positive, C3 levels remained low. Linear mixed model analysis showed that C3GN patients had higher soluble C5b-9 (sC5b-9) and lower properdin levels compared to DDD patients. With a median follow-up of 52 months, an overall benign outcome was observed with only six patients with eGFR below 90 ml/min/1.73 m(2) at last follow-up. CONCLUSIONS: We extensively described clinical and laboratory findings including complement features of an exclusively pediatric C3G cohort. Outcome was relatively benign, persistent low C3 correlated with C3NeF presence, and C3GN was associated with higher sC5b-9 and lower properdin levels. Prospective studies are needed to further elucidate the pathogenic mechanisms underlying C3G and guide personalized medicine with complement therapeutics. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00467-021-05221-6