Manual censoring of impedance tracings by the Wingate consensus reduces the number of impedance episodes, impacting on reflux categorization.

BACKGROUND: The Lyon consensus classifies the evidence of gastroesophageal reflux (GERD) based on endoscopic features and results of pH/impedance monitoring (pH-MII) including the post-reflux swallow-induced peristaltic wave index (PSPWI) and mean nocturnal baseline impedance (MNBI). The Wingate consensus established criteria to reduce inter-reviewer variability when assessing reflux episodes and PSPWI by impedance. This study aims to assess the influence of the Wingate criteria on the different pH-MII parameters obtained by automated analysis. METHODS: Thirty consecutive pH-MII off PPI were reviewed according to Wingate criteria. Number of impedance episodes and PSPWI were compared before and after censoring from automatic analysis. Reflux categorization according to Lyon consensus between censored and uncensored data was compared. Pearson correlations between impedance parameters and censored episodes were calculated. KEY RESULTS: Censoring the tracings significantly reduced the number of reflux episodes (66 [42-90.25] vs. 44.5 [21.5-61.5], p = 0.0105). Reasons for censoring were as follows: 1/ anterograde episode: 9.5 [6-13], 2/ impedance drop <50%: 1 [0-3], 3/ duration <4 s: 1 [0-2], 4/ <2 distal channels: 2.5 [1-4], and 5/ artifacts: 2 [1-5]. Censored episodes were in majority non-acid (16.5 [13-26.5] vs. 2 [0-4], p < 0.00001). Censoring altered the categorization of impedance episodes (<40 episodes, 6 vs. 13 for resp. uncensored vs. censored tracings, 40-80 episodes: 13 vs. 13, and >80 episodes: 11 vs. 4, p = 0.0264), but not the symptom index, the symptom association probability, or the categorization according to the Lyon consensus. Nevertheless, individual tracings were affected. The percentage of censored episodes was inversely correlated with the number of acidic impedance episodes (r = -0.62, p = 0.0002). CONCLUSION AND INFERENCES: Manual interpretation of impedance tracings based on the Wingate consensus reduces the number of impedance episodes, impacting on reflux categorization. Acidic reflux episodes are less likely to be censored, harboring a potential at improving automatic pH-MII analysis.

A Bitter Pill to Swallow: Pseudoachalasia Secondary to Oesophageal Deviation Resulting from Mediastinal Shift and Left Atrial Enlargement after Left Lower Lobectomy.

Pseudoachalasia, also known as secondary achalasia, is a rare clinical condition mimicking idiopathic achalasia but unrelated to primary loss of nitrergic innervation. It has mostly been attributed to malignancy infiltrating the oesophageal wall, but several other benign underlying pathologies have been reported. Because of similar manometric appearance, high-resolution manometry (HRM) of the oesophagus alone cannot distinguish between idiopathic achalasia and pseudoachalasia. Misdiagnosis can result in ineffective treatment by dilatation or even more invasive therapy. This is the first case-report of pseudoachalasia secondary to oesophageal deviation resulting from mediastinal shift and left atrial enlargement following prior left lower lobectomy. HRM, the gold standard for the diagnosis of achalasia, confirmed the incomplete relaxation of the lower oesophageal sphincter (LES) in absence of normal oesophageal peristalsis. However, additional workup with CAT scan and cardiac ultrasound identified an anatomical shift by the extrinsic mass effect resulting from the atrial enlargement, but without contrast retention at the LES.

A plethora of manifestations following a Mycoplasma pneumoniae infection: a case report.

Mycoplasma pneumoniae infection can present with a plethora of symptoms and result in a systemic vasculitis by activating a cascade of autoimmune reactions. In this case report, a young man without relevant past medical history was admitted to the hospital with diarrhea, abdominal pain and spiking fever. A CT-scan showed terminal ileitis. A 5-day broad spectrum antibiotic treatment (ciprofloxacin/clindamycin) did not result in any clinical improvement. On the contrary, the patient developed a cholestatic hepatitis, bilateral anterior uveitis and a dry cough. Extensive serological testing finally led to the diagnosis of a M. pneumoniae infection by paired serology (≥4-fold rise in IgG titer). In the diagnostic work-up, a PET-CT was performed and showed increased tracer uptake in the carotids and vertebral arteries, suggesting the diagnosis of vasculitis. After start of azithromycin and low-dose corticosteroids (0.5 mg/kg/day), a gradual clinical and biochemical improvement was observed. But subsequently, the patients relapsed and presented with an acute coronary syndrome. Coronary angiography revealed aneurysmatic deformation of the three coronary arteries, leading to the assumption of coronary vasculitis. Clinical improvement was achieved with high-dose corticosteroids (1 mg/kg/day). This case shows that M. pneumoniae is not merely a pulmonary infection, but that its primary symptoms can be diverse and misleading. All clinicians should be aware of its extrapulmonary manifestations.

A spontaneous animal model of intestinal dysmotility evoked by inflammatory nitrergic dysfunction.

BACKGROUND AND AIMS: Recent reports indicate the presence of low grade inflammation in functional gastrointestinal disorders (FGID), in these cases often called "post-inflammatory" FGIDs. However, suitable animal models to study these disorders are not available. The Biobreeding (BB) rat consists of a diabetes-resistant (BBDR) and a diabetes-prone (BBDP) strain. In the diabetes-prone strain, 40-60% of the animals develop diabetes and concomitant nitrergic dysfunction. Our aim was to investigate the occurrence of intestinal inflammation, nitrergic dysfunction and intestinal dysmotility in non-diabetic animals. METHODS: Jejunal inflammation (MPO assay, Hematoxylin&Eosin staining and inducible nitric oxide synthase (iNOS) mRNA expression), in vitro jejunal motility (video analysis) and myenteric neuronal numbers (immunohistochemistry) were assessed in control, normoglycaemic BBDP and diabetic BBDP rats. To study the impact of iNOS inhibition on these parameters, normoglycaemic BBDP rats were treated with aminoguanidine. RESULTS: Compared to control, significant polymorphonuclear (PMN) cell infiltration, enhanced MPO activity, increased iNOS mRNA expression and a decreased ratio of nNOS to Hu-C/D positive neurons were observed in both normoglycaemic and diabetic BBDP rats. Aminoguanidine treatment decreased PMN infiltration, iNOS mRNA expression and MPO activity. Moreover, it restored the ratio of nNOS to Hu-C/D positive nerves in the myenteric plexus and decreased the abnormal jejunal elongation and dilation observed in normoglycaemic BBDP rats. CONCLUSIONS: Aminoguanidine treatment counteracts the inflammation-induced nitrergic dysfunction and prevents dysmotility, both of which are independent of hyperglycaemia in BB rats. Nitrergic dysfunction may contribute to the pathophysiology of "low-grade inflammatory" FGIDs. Normoglycaemic BBDP rats may be considered a suitable animal model to study the pathogenesis of FGIDs.

Gastrointestinal motility changes and myenteric plexus alterations in spontaneously diabetic biobreeding rats.

BACKGROUND/AIMS: Type 1 diabetes is often accompanied by gastrointestinal motility disturbances. Vagal neuropathy, hyperglycemia, and alterations in the myenteric plexus have been proposed as underlying mechanism. We therefore studied the relationship between vagal function, gastrointestinal motiliy and characteristics of the enteric nervous system in the biobreeding (BB) rat known as model for spontaneous type 1 diabetes. METHODS: Gastric emptying breath test, small intestinal electromyography, relative risk-interval variability, histology and immunohistochemistry on antral and jejunal segments were performed at 1, 8 and 16 weeks after diabetes onset and on age-matched controls. RESULTS: We observed no consistent changes in relative risk-interval variability and gastric emptying rate. There was however, a loss of phases 3 with longer duration of diabetes on small intestinal electromyography. We found a progressive decrease of nitrergic neurons in the myenteric plexus of antrum and jejunum, while numbers of cholinergic nerve were not altered. In addition, a transient inflammatory infiltrate in jejunal wall was found in spontaneous diabetic BB rats at 8 weeks of diabetes. CONCLUSIONS: In diabetic BB rats, altered small intestinal motor control associated with a loss of myenteric nitric oxide synthase expression occurs, which does not depend on hyperglycemia or vagal dysfunction, and which is preceded by transient intestinal inflammation.

Longitudinal and cross-sectional factors associated with long-term clinical course in functional dyspepsia: a 5-year follow-up study.

OBJECTIVES: Functional dyspepsia (FD) is a heterogeneous disorder with different pathophysiological mechanisms underlying the symptom pattern, but little is known about its clinical course. The aims of this study were to study the long-term evolution of symptoms in a clinical FD population and to identify factors associated with outcome. METHODS: FD patients who previously underwent gastric function testing and filled out a dyspepsia symptom score (DSS) were contacted. At follow-up, patients indicated whether symptoms had worsened, remained unchanged, improved, or disappeared. Anxiety and depression, DSS, chronic fatigue symptoms, irritable bowel syndrome (IBS) comorbidity, and FD-specific quality of life (QoL) were assessed using mailed questionnaires. Bivariate associations between different patient characteristics and DSS and QoL at follow-up were tested; multiple linear regression was used to identify factors associated with the outcomes, both longitudinally and cross-sectionally. RESULTS: Data were obtained from 253 patients (84.9% of the eligible and consenting population (n=298) and 53.2% of the original population (n=476)). The mean duration of follow-up was 68±2 months. Disappeared, improved, unchanged, and worsened symptoms were reported by 17.4, 38.3, 30.8, and 13.4% of the patients, respectively. Correlations between dyspepsia symptoms at initial visit and follow-up were small to moderate in magnitude. DSS at initial visit and trait anxiety were longitudinally associated with DSS at follow-up, with a trend found for weight loss; depression, chronic fatigue, and IBS at follow-up were cross-sectionally associated with DSS. Trait anxiety, weight loss, and DSS at initial visit were independently associated with QoL at follow-up; depression as well as DSS and chronic fatigue at follow-up were cross-sectionally associated. CONCLUSIONS: About half of FD patients reported disappeared or improved symptoms after a mean follow-up of 5 years. Although stability of symptom levels is low to moderate, DSS at initial visit, trait anxiety, and initial weight loss are more strongly associated with outcome than gastric sensorimotor function.

Contribution of different triggers to the gastric accommodation reflex in humans.

Accommodation of the stomach consists of a vagally mediated relaxation of the proximal stomach, providing the meal with a reservoir. Our aim was to study whether, similar to other vagally mediated processes, the accommodation reflex is also determined by cephalic, oropharyngeal, gastric, and intestinal phases. Eleven healthy subjects underwent in randomized order five gastric barostat studies and two satiety drinking tests. In all studies, isobaric tone measurements (at minimal distending pressure + 2 mmHg) were performed 20 min before and 20 min after a nutrient stimulus. The stimuli included only visual and olfactory exposure to a meal (cephalic stimulation), taking liquid nutrient in the mouth without swallowing (sham feeding), ingestion of a 200-ml 300-kcal nutrient meal with blocked outflow to the pylorus (gastric retention), and meal infusion through a nasointestinal tube (duodenal instillation), or normal ingestion (control). During satiety testing, subjects ingested liquid nutrient at a fixed rate of 15 ml/min until maximum satiety, with an inflated or deflated intrapyloric balloon assembly. Progressively bigger gastric relaxatory responses were seen with cephalic stimulation (18 +/- 19 ml), sham feeding (54 +/- 21 ml), gastric retention (95 +/- 47), duodenal instillation (144 +/- 33), and control (232 +/- 33 ml). The amount of nutrient ingested at maximum satiety was significantly lower with an inflated intrapyloric balloon (1,223 +/- 103 vs. 1,392 +/- 124 ml, P < 0.05). The accommodation reflex in humans lacks a cephalic phase, but it can be activated from the oropharynx, the stomach, and the duodenum. Blocking passage to the duodenum significantly decreases the amplitude of the accommodation reflex and induces early satiety.

Pathogenesis and therapy for idiopathic dyspepsia.

Functional dyspepsia (FD) is one of the most common gastrointestinal disorders. This review summarizes recent progress in our understanding of the pathogenesis and therapy for FD. Although distinction among FD, irritable bowel syndrome, and reflux disease is difficult in population-based studies, separate entities can be recognized in patients who seek medical attention. The pathogenesis of FD remains unclear, but recent studies have demonstrated a role for acute gastrointestinal infection in triggering FD and in genetic polymorphisms of G-proteins in predisposing to FD. The role of abnormalities in gastric motor function, visceral hypersensitivity, and psychosocial factors in the pathophysiology of dyspeptic symptoms has been the topic of multiple studies. Treatment options for FD remain limited. Recent studies have focused on acid-suppressive drugs and on novel prokinetics. Progress in our understanding of the pathogenesis and pathophysiology of FD may lead to new or improved treatment modalities. Areas of major advances are the role of infection and genetic predisposition and studies on the role of abnormalities in gastric motility and sensitivity.