The Lyon Consensus provides conclusive criteria for and against the diagnosis of gastro-oesophageal reflux disease (GERD), and adjunctive metrics that consolidate or refute GERD diagnosis when ...primary criteria are borderline or inconclusive. An international core and working group was assembled to evaluate research since publication of the original Lyon Consensus, and to vote on statements collaboratively developed to update criteria. The Lyon Consensus 2.0 provides a modern definition of actionable GERD, where evidence from oesophageal testing supports revising, escalating or personalising GERD management for the symptomatic patient. Symptoms that have a high versus low likelihood of relationship to reflux episodes are described. Unproven versus proven GERD define diagnostic strategies and testing options. Patients with no prior GERD evidence (unproven GERD) are studied using prolonged wireless pH monitoring or catheter-based pH or pH-monitoring off antisecretory medication, while patients with conclusive GERD evidence (proven GERD) and persisting symptoms are evaluated using pH-impedance monitoring while on optimised antisecretory therapy. The major changes from the original Lyon Consensus criteria include establishment of Los Angeles grade B oesophagitis as conclusive GERD evidence, description of metrics and thresholds to be used with prolonged wireless pH monitoring, and inclusion of parameters useful in diagnosis of refractory GERD when testing is performed on antisecretory therapy in proven GERD. Criteria that have not performed well in the diagnosis of actionable GERD have been retired. Personalisation of investigation and management to each patient's unique presentation will optimise GERD diagnosis and management.
LINKED CONTENT
This article is linked to Wong et al papers. To view these articles, visit https://doi.org/10.1111/apt.16561 and https://doi.org/10.1111/apt.16783
LINKED CONTENT
This article is linked to Wong et al and Kahrilas papers. To view these articles, visit https://doi.org/10.1111/apt.16561 and https://doi.org/10.1111/apt.16572
Summary
Background
The pathogenesis of gastro‐oesophageal reflux disease (GERD) is complex and multifactorial. The oesophageal hypervigilance and anxiety scale (EHAS) is a novel cognitive‐affective ...evaluation of visceral sensitivity.
Aims
To investigate the interrelationship between EHAS and reflux symptom severity, psychological stress, acid reflux burden, phenotypes, and oesophageal mucosal integrity in patients with GERD.
Methods
Patients with chronic reflux symptoms and negative endoscopy underwent 24‐hour impedance‐pH monitoring for phenotyping, acid reflux burden, and mucosal integrity with mean nocturnal baseline impedance (MNBI) calculation. Validated scores for patient‐reported outcomes, including EHAS, GERD questionnaire (GERDQ), State‐Trait Anxiety Inventory score, and Taiwanese Depression Questionnaire score, were recorded.
Results
We enrolled 105 patients, aged 21‐64 years (mean, 48.8), of whom 58.1% were female; 27 had non‐erosive reflux disease, 43 had reflux hypersensitivity and 35 had functional heartburn. There were no significant differences in sex, EHAS, GERDQ, questionnaires of depression or anxiety among GERD phenotypes. EHAS was significantly correlated with GERDQ, questionnaires of depression and anxiety (P < 0.05). However, there were no significant correlations between GERDQ and questionnaires of depression or anxiety. Regarding patient‐reported outcomes, GERDQ positively correlated with acid exposure time and negatively correlated with MNBI (P < 0.05).
Conclusions
EHAS associates with reflux symptom severity and psychological stress but not with acid reflux burden or mucosal integrity. Thus, EHAS assessment shows promise in assessment of subjective patient outcome and satisfaction with treatment, a hitherto unmet clinical need.
The putative modulators for reflux symptom severity.
In this population-based propensity score matched (PSM) cohort study, we aimed to investigate the risk of developing dementia with the use of acid suppressants, including proton pump inhibitors ...(PPIs) and histamine-2 receptor antagonists (H2 antagonists). Cohorts of PPI users (n = 2,778), H2 antagonist users (n = 6,165), and non-users (n = 86,238) were selected from a dataset covering the years 2000 to 2010 in Taiwan's National Health Insurance Research Database. Patients in the three groups were PSM at a ratio of 1:1 within each comparison cohort (CC). Three CCs were created: (1) PPI users compared to non-users (CC1, n = 2,583 pairs); (2) H2 antagonist users compared to non-users (CC2, n = 5,955 pairs); and (3) PPI users compared to H2 antagonist users (CC3, n = 2,765 pairs). A multivariable robust Cox proportional hazard model was used to estimate the adjusted hazard ratio (aHR) and the 95% confidence interval (CI) for the risk of developing dementia. The multivariable analysis results show that the aHR of developing dementia during the follow-up period was 0.72 (CC1: 95% CI = 0.51-1.03, P = 0.07) for PPI users and 0.95 (CC2: 95% CI = 0.74-1.22, P = 0.69) for H2 antagonist users, when compared to non-users. Between the patients using acid suppressants, there was no difference between PPI and H2 antagonist users in the risk of developing dementia (CC3: aHR = 0.82, 95% CI = 0.58-1.17, P = 0.28). In conclusion, no association was observed between the use of acid suppressants and the risk of developing dementia in any of the three CCs. Further, randomized controlled trials are warranted to confirm this relationship.
Existing nonvolatile ternary content-addressable-memory (nvTCAM) suffers from limited word-length (WDL), large write-energy (E W ) and search-energy (E S ), and large cell area (A). This paper ...develops a 3T1R nvTCAM cell using a single multiple-level cell (MLC)-resistive RAM (ReRAM) device to achieve long WDL, lower E W and E S , and reduced cell area. Two peripheral control schemes were developed, dual-replica-row selftimed and invalid-entry power consumption suppression (IEPCS), for the suppression of dc current in 3T1R nvTCAM cells in order to reduce E S . Two versions of the IEPCS scheme were developed (basic and charge-recycle-controlled) to alter the tradeoff between area overhead and power consumption in the updating of invalid-bits. A 128 b × 64 b 3T1R nvTCAM macro was fabricated using back-end-of-line ReRAM under 90-nm CMOS process. The fabricated MLC-based 3T1R nvTCAM macro achieved sub-1-ns search-delay and sub-6-ns wake-up time with supply voltage of 1 V and WDL = 64 b.
Background
Ineffective esophageal motility (IEM) is the most common motility disorder. However, little is known about its pathophysiology. Vagal afferent nerves convey esophageal intraluminal bolus ...information to solitary nucleus, which is likely to be involved with esophageal primary and secondary peristalsis (SP). We hypothesized that altered mucosal sensory afferents underlie the pathogenesis of IEM.
Methods
We prospectively collected esophageal biopsies from 38 patients with proton pump inhibitor‐refractory reflux symptoms from January to December 2019. All patients underwent high‐resolution manometry for the evaluation of primary and secondary peristalsis, and off‐PPI 24‐h impedance‐pH studies. Biopsies were analyzed using immunohistochemistry for identification of calcitonin gene‐related peptide‐immunoreactive (CGRP‐IR) nerves and qPCR for mRNA expression of potential mechanoreceptors.
Key Results
Overall 32 patients were finally analyzed which consisted of 11 patients with normal motility and 21 patients with IEM. The position of mucosal CGRP‐IR nerves from the esophageal lumen did not differ between the two groups (the proximal esophagus (p = 0.52), the mid‐esophagus (p = 0.92), the distal esophagus (p = 0.29)) with the similar reflux profile. No difference was seen in the position of CGRP‐IR nerves between patients with successful triggering of SP and those unable to trigger SP. There was also no difference in mRNA expression of each potential mechanoreceptors (TRPA1, TRPV1, TRPV4, ASIC1, ASIC3) between the two groups.
Conclusions and Inferences
Our study showed that mucosal sensory afferents nerve position and mRNA expression of potential mechanoreceptors did not correlate to weak esophageal contraction.
Mucosal afferents nerve position does not differ between patients with normal motility and those with IEM.
Background
Bismuth quadruple therapy is the treatment of choice for the first‐line therapy of Helicobacter pylori infection in areas of high clarithromycin resistance. Currently, the impact of the ...promising treatment on gut microbiota remains unclear.
Aim
To investigate the short‐term and long‐term impacts of bismuth quadruple therapy on gut microbiota.
Methods
Adult patients with H. pylori‐related gastritis were treated with 14‐day bismuth quadruple therapy. Fecal samples were collected before treatment at week 2, week 8, and week 48. Nucleic acid extraction from fecal samples was performed. The V3‐V4 region of the bacterial 16S rRNA gene was amplified by polymerase chain reaction and sequenced with the MiSeq followed by data analysis using Qiime pipeline.
Results
Eleven patients received complete follow‐up. Before treatment, the most abundant phyla were Firmicutes (45.3%), Bacteroidetes (24.3%), Proteobacteria (9.9%), and Actinobacteria (5.0%). At the end of bismuth therapy, the relative abundances of Bacteroidetes and Actinobacteria decreased to 0.5% (P < .001) and 1.3% (P = .038), respectively. Additionally, the relative abundance of Verrucomicrobia also decreased from 3.2% to 1.11E−3% (P = .034). In contrast, the relative abundances of Proteobacteria and Cyanobacteria increased (P < .001 and P = .003, respectively). At week 8, the relative abundances of all phyla restored to the levels at baseline. The relative abundances of all phyla at week 48 also did not significantly differ from those at baseline. During eradication therapy, 6 patients (55%) reported at least 1 adverse event. The relative abundance of phylum Proteobacteria in patients with adverse effects was more than that in patients without adverse effects (68.7% ± 8.8% vs 43.4% ± 25.5%; P = .048).
Conclusions
Bismuth quadruple therapy for H. pylori eradication can lead to short‐term dysbiosis of gut microbiota. The increase in Proteobacteria in gut microbiota may attribute to the development of adverse effects during bismuth quadruple therapy.
Background and Aim
Ineffective esophageal motility (IEM) is associated with gastroesophageal reflux disease. Secondary peristalsis contributes to esophageal clearance. Prucalopride promotes secondary ...peristalsis by stimulating 5‐hydroxytrypatamine 4 receptors in the esophagus. We aimed to determine whether prucalopride would augment secondary peristalsis in gastroesophageal reflux disease patients with IEM.
Methods
After a baseline recording of primary peristalsis, secondary peristalsis was stimulated by slow and rapid mid‐esophageal injections of air in 15 patients with IEM. Two separate sessions with 4‐mg oral prucalopride or placebo were randomly performed.
Results
Prucalopride significantly increased primary peristaltic wave amplitude (68.1 ± 10.0 vs 55.5 ± 8.8 mmHg, P = 0.02). The threshold volume for triggering secondary peristalsis was significantly decreased by prucalopride during slow (9.3 ± 0.8 vs 12.0 ± 0.8 mL; P = 0.04) and rapid air injection (4.9 ± 0.3 vs 7.1 ± 0.1 mL; P = 0.01). Secondary peristalsis was triggered more frequently after application of prucalopride (55% 43–70%) than placebo (45% 33–50%) (P = 0.008). Prucalopride did not change pressure wave amplitudes during slow air injection (84.6 ± 8.1 vs 57.4 ± 13.8 mmHg; P = 0.19) or pressure wave amplitudes during rapid air injection (84.2 ± 8.6 vs 69.5 ± 12.9 mmHg; P = 0.09).
Conclusions
Prucalopride enhances primary peristalsis and mechanosensitivity of secondary peristalsis with limited impact on secondary peristaltic activities in IEM patients. Our study suggests that prucalopride appears to be useful in augmenting secondary peristalsis in patients with IEM only via sensory modulation of esophageal secondary peristalsis.
PDF
