Mark R Fox

• MD
• Medical Doctor at University Hospital Zürich and Klinik Arlesheim

Introduction The Lyon 2.0 Consensus recommends prolonged, 96-hour, wireless pH-studies as the preferred diagnostic tool in unproven GERD when available.¹ This decision was based on the finding that prolonged pH measurements provide a higher diagnostic yield than 24-hr studies. However, the pH sensor may detach early, and 48-hour studies are routine...

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...

Frequent Gastro-Intestinal Disorders: Management of Functional Dyspepsia and Irritable Bowel Syndrome in Clinical Practice Abstract: Functional dyspepsia (FD) and irritable bowel syndrome (IBS), two common gastrointestinal entities with overlapping symptoms, should be diagnosed according to Rome IV criteria. This includes one or more of the followi...

Background: Gastroesophageal reflux disease seems more frequent after laparoscopic sleeve gastrectomy (LSG) than Roux-en-Y gastric bypass (LRYGB). Retrospective case series have raised concerns about a high incidence of Barrett esophagus (BE) after LSG. Objective: This prospective clinical cohort study compared the incidence of BE ≥5 years after...

Zusammenfassung Unangenehmes Völlegefühl nach den Mahlzeiten, Schmerzen im Oberbauch, Übelkeit und andere dyspeptische Symptome sind in der Allgemeinbevölkerung weit verbreitet, beeinträchtigen die Lebensqualität und verursachen erhebliche Kosten im Gesundheitswesen. In dieser Übersichtsarbeit wird die Rom-IV-Definition der funktionellen Dyspepsie...

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated condition causing esophageal symptoms, particularly dysphagia. Despite the important progress in the treatment of EoE, a significant proportion of patients continue to report symptoms that negatively impact quality of life. Esophageal manometry is used to assess motility and function, but...

INTRODUCTION Currently, there is a lack of information regarding the frequency of hospital admissions for hiccups and exploring the underlying causes. This study reports hospital admissions for hiccups in the United States (U.S.). METHODS A cross-sectional study was performed, utilizing information from the U.S. National Inpatient Sample (NIS) from...

LINKED CONTENT This article is linked to Yadlapat et al papers. To view these articles, visit https://doi.org/10.1111/apt.17180 and https://doi.org/10.1111/apt.17218

Background Scintigraphy is used for overall assessment of gastric emptying. Adherence to an international consensus protocol is recommended to ensure quality; however, this has not been widely adopted because preparation of the “egg‐beater” meal is inconvenient in clinical practice. In this report, we audit the tolerability and the results of gastr...

Purpose of review: Provocative tests have been advocated to address limitations of high-resolution manometry (HRM) with wet swallows. We describe the commonly used provocative manometric manoeuvres [rapid drink challenge (RDC), multiple rapid swallows (MRS), solid swallows and the solid test meal (STM)], compare their diagnostic yield and accuracy...

Recurrent and persistent bouts of hiccups impact the quality of life by interfering with eating, social interaction and work. Popular home remedies, such as breath holding and drinking ice water, target activity in the vagal and phrenic nerves that are thought to trigger these repetitive, myoclonic contractions. However, the pathophysiology of hicc...

LINKED CONTENT This article is linked to Wu et al papers. To view these articles, visit https://doi.org/10.1111/apt.16812

Nausea, vomiting and abdominal pain in diabetic patients are often attributed to diabetic gastropathy (DG). Post-pyloric ("jejunal") enteral nutrition (JN) may improve nutrition and glycaemia in difficult cases. The acute effects of JN on postprandial symptoms and gastric function in DG patients has not been studied. DG patients with moderate to se...

La Clasificación de Chicago v4.0 (CCv4.0) es el esquema actualizado para clasificar las alteraciones de la motilidad esofágica utilizando la métrica de la manometría de alta resolución (HRM). Para desarrollar la CCv4.0, 52 expertos internacionales diversos separados en siete subgrupos de trabajo utilizaron una metodología formalmente validada, en u...

Zusammenfassung. Die anorektale Funktionsdiagnostik ermöglicht die Messung des Analsphinkterdrucks, die Evaluierung der Rektumsensibilität sowie die Überprüfung der rektoanalen Reflexe, die wesentliche Elemente der Beurteilung der Darmentleerung darstellen. Sie wird mit einem Ballonexpulsionstest kombiniert, um sicherzustellen, dass die manometrisc...

Introduction Measurement of breath hydrogen (H2) and methane (CH4) excretion after ingestion of test-carbohydrates is used for different diagnostic purposes. There is a lack of standardization among centers performing these tests and this, together with recent technical developments and evidence from clinical studies, highlight the need for a Europ...

Objective At high altitude (HA), acute mountain sickness (AMS) is accompanied by neurologic and upper gastrointestinal symptoms (UGS). The primary aim of this study was to test the hypothesis that delayed gastric emptying (GE), assessed by ¹³C‐octanoate breath testing (OBT), causes UGS in AMS. The secondary aim was to assess post‐gastric mechanisms...

This cross-sectional study evaluates the usefulness of the forced inspiratory suction and swallow tool for stopping hiccups in a group of volunteers who completed an online questionnaire..

Background Quarantine with social distancing has reduced transmission of COVID‐19; however, fear of the disease and these remedial measures cause anxiety and stress. It is not known whether these events have impacted the prevalence of gastrointestinal (GI) symptoms and disorders of brain‐gut interaction (DGBI). Methods An online platform evaluated...

Background: The efficacy and factors associated with patient outcomes for a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (LFD) compared with traditional dietary advice (TDA) based on modified National Institute for Clinical Excellence guidelines for irritable bowel syndrome with diarrhea (IBS-D) in regions...

The Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high‐resolution manometry (HRM). A key feature of CCv.4.0 is the more rigorous and expansive protocol that incorporates single wet swallows acquired in different positions (supine, upright) and provocative testing, incl...

Objective Acid exposure time (AET) from ambulatory pH studies and reflux oesophagitis are independent measurements used by the Lyon classification to diagnose GORD. This study aimed to validate AET reference ranges and diagnostic thresholds by analysis of 96-hour wireless pH studies from healthy, asymptomatic controls (HCs) and patients with and wi...

Background Chronic constipation is a prevalent disorder that affects quality of life of patients and consumes resources in healthcare systems worldwide. In clinical practice, it is still considered a challenge as clinicians frequently are unsure as to which treatments to use and when. Over a decade ago, a Neurogastroenterology and Motility journal...

Introduction Technology now allows up to 96-hour wireless pH-recording in clinical practice; however, no normal values exist for this methodology. This study acquired 96-hour esophageal pH recordings in healthy controls (HC) and compared these values against measurements in patients with endoscopic evidence of gastroesophageal reflux disease (GORD)...

Introduction Proton pump inhibitors (PPIs) are widely prescribed for gastro-oesophageal reflux disease (GORD) symptoms. The ‘PPI test’ is frequently used in lieu of formal testing. It has been shown previously that, with 48 hr pH monitoring, a 2-week PPI trial has limited accuracy for GERD diagnosis. However, it is possible that restricting to 48 h...

Several characteristics make magnetic resonance imaging (MRI) an useful technique for the assessment of digestive anatomy and function in health and disease. MRI acquires large field-of-view, dynamic, high-resolution, three-dimensional (3D) image data with excellent soft-tissue contrast in less than a second; it does not expose subjects to ionizing...

Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high‐resolution manometry (HRM). Fifty‐two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two‐years to develop CCv4.0. Key updates in CCv.4.0 consist of a m...

Since publication of Chicago Classification version 3.0 in 2015, the clinical and research applications of high‐resolution manometry (HRM) have expanded. In order to update the Chicago Classification, an International HRM Working Group consisting of 52 diverse experts worked for two years and utilized formally validated methodologies. Compared with...

Background This prospective study applied magnetic resonance imaging (MRI) to assess the effect of laparoscopic sleeve gastrectomy (LSG) on gastric structure and function. The impact of these changes on patient outcomes was analyzed.Method Obese patients without gastrointestinal symptoms referred for bariatric surgery were recruited prospectively....

Introduction: The development of a clinical guideline is a challenging process. National and international organizations have established a variety of approaches, grading systems, evaluation scales and voting modes, however a practical description which illustrates all steps from starting the initiative to publication and dissemination of the guid...

The cover image is based on the Original Article Volume and position change of the stomach during gastric accommodation and emptying: a detailed three‐dimensional morphological analysis based on MRI by Mark Fox, Anupam Pal, and Sreerup Banerjee., https://doi.org/10.1111/nmo.13865

Background The incidence of de novo gastroesophageal reflux disease (GERD) after LSG is substantial. However, an objective correlation with the structural gastric and EGJ changes has not been demonstrated yet. We aimed to prospectively evaluate the effects of laparoscopic sleeve gastrectomy (LSG) on the structure and function of the esophagogastric...

Background The proximal and distal regions of the stomach are thought to have different roles during gastric accommodation and emptying; however, regional changes in gastric structure and function during and after a meal have not been described in detail. This study applied non‐invasive imaging to study changes in regional gastric volume and morpho...

Objectives: Gastrointestinal involvement and impaired nutritional status are frequent in patients with systemic sclerosis (SSc). Hereby, we hypothesised that micronutrients and/or prealbumin could be deficitary in SSc. Methods: Patients with SSc and very early SSc (veSSc) were prospectively included. Clinical assessment, data recording and quali...

Background: Standard high-resolution manometry (HRM) protocols are based on 10 single water swallows acquired in the supine position. Aims: To assess the impact of position, rapid drink challenge and solid test meal on the diagnosis of oesophageal motility disorders. Methods: Seventy-two healthy volunteers (20-76 years) and 366 consecutive pat...

Background & aims: Wireless pH monitoring measures esophageal acid exposure time (AET) for up to 96 hrs. We evaluated competing methods of analysis of wireless pH data. Methods: Adult patients with persisting reflux symptoms despite acid suppression (n=322, 48.5±0.9 y, 61.7% women) from 2 tertiary centers were evaluated using symptom questionnai...

Background & aims: It is not clear how rapid ascent to high altitude causes the gastrointestinal symptoms of acute mountain sickness (AMS). We assessed the incidence of endoscopic lesions in the upper gastrointestinal tract in healthy mountaineers after rapid ascent to high altitude, their association with symptoms, and their pathogenic mechanisms...

Lactose is the main source of calories in milk, an essential nutriedigestion, patients with visceral hypersensitivity nt in infancy and a key part of the diet in populations that maintain the ability to digest this disaccharide in adulthood. Lactase deficiency (LD) is the failure to express the enzyme that hydrolyses lactose into galactose and gluc...

Dark chocolate is claimed to have effects on gastrointestinal function and to improve well-being. This randomised controlled study tested the hypothesis that cocoa slows gastric emptying and intestinal transit. Functional brain imaging identified central effects of cocoa on cortical activity. Healthy volunteers (HV) ingested 100 g dark (72 % cocoa)...

Zusammenfassung Die Ösophagusmanometrie erlaubt eine genaue Beurteilung der Kontraktilität der Speiseröhre und ist deshalb das Referenzverfahren für die Diagnostik ösophagealer Motilitätsstörungen. Aussagekraft und Bedeutung der Methode haben durch die Einführung der hochauflösenden Ösophagusmanometrie (HRM) noch weiter gewonnen, welche die funktio...

Background and aims Lactulose is a common food ingredient and widely used as a treatment for constipation or hepatic encephalopathy and a substrate for hydrogen breath tests. Lactulose is fermented by the colon microbiota resulting in the production of hydrogen (H2). H2 is a substrate for enteropathogens including Salmonella Typhimurium (S. Typhimu...

Objective This study assessed whether high‐resolution manometry (HRM) with a test meal can detect clinically relevant, abnormal motility already in very early systemic sclerosis (SSc) and whether this finding is associated with subsequent disease progression. Methods This prospective, longitudinal cohort study recruited 68 consecutive SSc patients...

Zusammenfassung Die gastroösophageale Refluxkrankheit stellt die häufigste Ursache für Symptome des oberen Gastrointestinaltrakts dar. Der Säure-Reflux in der postprandialen Phase ist der prädominante Faktor der gastroösophagealen Refluxkrankheit (gastro-esophageal Reflux disease, GERD) und führt zu Beschwerden wie Sodbrennen und saurem Aufstoßen....

Background and aims: Lactulose is a common food ingredient and widely used as a treatment for constipation or hepatic encephalopathy and a substrate for hydrogen breath tests. Lactulose is fermented by the colon microbiota resulting in the production of hydrogen (H2). H2 is a substrate for enteropathogens including Salmonella Typhimurium (S. Typhim...

Background: Current investigations of gastric emptying rarely identify the cause of symptoms or provide a definitive diagnosis in patients with dyspepsia. This study assessed gastric function by magnetic resonance imaging (MRI) using the modular "Nottingham test meal" (NTM) in healthy volunteers (HVs). Methods: The NTM comprises (a) 400 mL liqui...

Objectives: To investigate the performance of MR-defecography (MRD) in lateral body position as an alternative to supine position. Methods: 22 consecutive patients (16 females; mean age 51 ± 19.4) with obstructed defecation and 20 healthy volunteers (11 females; mean age 33.4 ± 11.5) underwent MRD in a closed-configuration 3T-MRI in supine and l...

Esophageal diseases are highly prevalent and carry significant socioeconomic burden. Despite the apparently simple function of the esophagus, we still struggle to better understand its physiology and pathophysiology. The assessment of large data sets and application of multiscale mathematical organ models have gained attention as part of the Physio...

Symptoms related to abnormal gastrointestinal motility and function are common. Oropharyngeal and oesophageal dysphagia, heartburn, bloating, abdominal pain and alterations in bowel habits are among the most frequent reasons for seeking medical attention from internists or general practitioners and are also common reasons for referral to gastroente...

Background Ineffective oesophageal motility (IEM) is frequent in patients with systemic sclerosis (SSc). High-resolution oesophageal manometry (HRM) is the reference standard test for oesophageal motility and addition of a test meal increases diagnostic sensitivity and specificity. Objectives This study assessed whether using a test meal instead o...

Introduction The cause of IBS is uncertain; however, food intolerance shares many features with this condition. Consumption of Fermentable Oligo–, Di– and Mono–saccharides And Polyols (FODMAPs) has been shown to induce IBS-type symptoms (Shephard 2008) and clinical trials have shown that a low FODMAP diet can improve symptoms in this patient group...

Introduction Diabetic gastroparesis (DG) affects up to 20% patients with type I Diabetes Mellitus (DM). Impaired gastric function is thought to be the cause of nausea, vomiting, abdominal pain and impaired glycaemic control. DG does not respond reliably to intensive insulin regimes or prokinetic medications. Jejunal nutrition (JN) is an option in p...

Esophageal symptoms can arise from gastroesophageal reflux disease (GERD) as well as other mucosal and motor processes, structural disease, and functional esophageal syndromes. GERD is the most common esophageal disorder, but diagnosis may not be straightforward when symptoms persist despite empiric acid suppressive therapy and when mucosal erosion...

Chronic diarrhoea is a common problem, hence clear guidance on investigations is required. This is an updated guideline from 2003 for the investigations of chronic diarrhoea commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG). This document has undergone significant revision in content thro...

This corrects the article DOI: 10.1038/nrgastro.2017.130.

This corrects the article DOI: 10.1038/nrgastro.2017.132.

Disturbances of gastric, intestinal and colonic motor and sensory functions affect a large proportion of the population worldwide, impair quality of life and cause considerable health-care costs. Assessment of gastrointestinal motility in these patients can serve to establish diagnosis and to guide therapy. Major advances in diagnostic techniques d...

BACKGROUND: Advances in clinical measurement of esophageal motility and function have improved the assessment of swallowing disorders and reflux symptoms. Variation in data acquisition, analysis, and reporting exists and impacts on diagnosis and management. AIMS AND METHODS: This study examined variation in esophageal manometry methodology between...

Clinical history, questionnaire data and response to antisecretory therapy are insufficient to make a conclusive diagnosis of GERD in isolation, but are of value in determining need for further investigation. Conclusive evidence for reflux on oesophageal testing include advanced grade erosive oesophagitis (LA grades C and D), long-segment Barrett’s...

Functional dyspepsia is a prevalent functional gastrointestinal disorder that can significantly erode the quality of life of sufferers and places a major cost burden on healthcare services. In this article, we review the recent literature, selecting the information we consider relevant since it has changed our clinical management of patients with f...

GERD is a common condition worldwide. Key mechanisms of disease include abnormal oesophagogastric junction structure and function, and impaired oesophageal clearance. A therapeutic trial of acid-suppressive PPI therapy is often the initial management, with endoscopy performed in the setting of alarm symptoms and to exclude other conditions. If symp...

High-resolution manometry (HRM) and new analysis algorithms, summarized in the Chicago Classification, have led to a restructured classification of oesophageal motility disorders. This advance has led to increased detection of clinically relevant disorders, in particular achalasia. It has become apparent that the cardinal feature of achalasia - imp...

Background: Advances in clinical measurement of esophageal motility and function have improved the assessment of swallowing disorders and reflux symptoms. Variation in data acquisition, analysis, and reporting exists and impacts on diagnosis and management. Aims and methods: This study examined variation in esophageal manometry methodology betwe...

Background: Current investigations of stomach function are based on small test meals that do not reliably induce symptoms and analysis techniques that rarely detect clinically relevant dysfunction. This study presents the reference intervals of the modular "Nottingham test meal" (NTM) for assessment of gastric function by gamma scintigraphy (GSc)...

Background: High-resolution manometry (HRM) has resulted in new revelations regarding the pathophysiology of gastro-esophageal reflux disease (GERD). The impact of new HRM motor paradigms on reflux burden needs further definition, leading to a modern approach to motor testing in GERD. Methods: Focused literature searches were conducted, evaluati...

Background: An international group of experts evaluated and revised recommendations for ambulatory reflux monitoring for the diagnosis of gastro-esophageal reflux disease (GERD). Methods: Literature search was focused on indications and technical recommendations for GERD testing and phenotypes definitions. Statements were proposed and discussed...

Background: Ano-rectal manometry (ARM) is the most commonly performed investigation for assessment of anorectal dysfunction. Its use is supported by expert consensus documents and international guidelines. Variation in technology, data acquisition, and analysis affect results and clinical interpretation. This study examined variation in ARM betwee...

Background: As treatments for constipation become increasingly available, it is important to know when to progress along the treatment algorithm if the patient is not better. Aim: To establish the definition of failure of a treatment to provide adequate relief (F-PAR) to support this management and referral process in patients with chronic const...

Background: Etiology of gastro-esophageal reflux disease (GERD) is multifactorial, but incompetence of the esophago-gastric junction (EGJ) appears to be of crucial importance. Established manometric parameters for assessment of EGJ barrier function are sub-optimal, potentially because they reflect only a very brief (up to 30 seconds), not necessar...

Background: Criteria for transient lower esophageal sphincter relaxations (TLESRs) are well-defined for Dentsleeve manometry. As high-resolution manometry (HRM) is now the gold standard to assess esophageal motility, our aim was to propose a consensus definition of TLESRs using HRM. Methods: Postprandial esophageal HRM combined with impedance wa...

Background/aims: The Chicago Classification for diagnosis of esophageal motility disorders by high-resolution manometry (HRM) is based on single water swallows (SWS). Emerging data suggest that a "Rapid Drink Challenge" (RDC) increases sensitivity for motility disorders. This study establishes normal values and diagnostic thresholds for RDC in cli...

Small intestinal bacterial overgrowth (SIBO) has been implicated in the pathogenesis of irritable bowel syndrome (IBS). Psychosocial factors and low-grade colonic mucosal immune activation have been suggested to play important roles in the pathophysiology of IBS. In total, 94 patients with IBS and 13 healthy volunteers underwent a 10 g lactulose hy...

Introduction Despite advances in HRM and pH monitoring there is wide variation in technique and technology while reporting is often subjective and open to interpretation. This study assesses current practice around the world. Methods Through an on-line platform (Qualtrics LLC), a survey was distributed to unselected oesophageal units through inter...

Dietary factors have important effects on gastrointestinal function. Any factor that increases gastric distention (e. g. meal volume), slows gastric emptying (e. g. calorie load), or promotes acid secretion (e. g. calcium, certain amino acids) increases the risk of gastroesophageal reflux. Further factors that modulate esophageal sensitivity (e. g....

The first priority in the clinical assessment of patients with difficulty swallowing is to distinguish between pharyngeal and esophageal dysphagia. Then, after exclusion of structural and mucosal pathology by endoscopy, physiological investigations are performed to identify the cause of esophageal dysfunction and symptoms. The aim of manometry is t...

Hiccups are familiar to everyone, but remain poorly understood. Acute hiccups can often be terminated by physical manoeuvres. In contrast, persistent and intractable hiccups that continue for days or months are rare, but can be distressing and difficult to treat. To review the management of hiccups, including a systematic review of reported efficac...

Introduction Oesophageal physiology testing has advanced markedly in the last decade. Tools such as high resolution manometry (HRM) have become widely available and have enhanced our understanding of oesophageal (dys)function. However this has also led to wide variation in testing methods and analysis. Before a consensus is built towards setting qu...

Objectives: Enhanced characterization of esophageal peristaltic and sphincter function provided by esophageal pressure topography (EPT) offers a potential diagnostic advantage over conventional line tracings (CLT). However, high-resolution manometry (HRM) and EPT require increased equipment costs over conventional systems and evidence demonstratin...

Figure S1. Analysis population flowchart. AE, adverse event; PD, pharmocodynamic; pH/impedance, combined pH, and multichannel intraluminal impedance.

Patients with obstructive defecation have abnormalities of anorectal function and/or structure. Conventional anorectal manometry (ARM) can identify abnormal function and behaviour (dyssynergia); however agreement between manometry and defecography is only fair. High resolution (HR-)ARM may improve diagnostic agreement by differentiating pressure ef...

The Chicago Classification (CC) of esophageal motility disorders, utilizing an algorithmic scheme to analyze clinical high-resolution manometry (HRM) studies, has gained acceptance worldwide. This 2014 update, CC v3.0, developed by the International HRM Working Group, incorporated the extensive clinical experience and interval publications since th...

Background Approximately, 20–30% of patients with gastro-esophageal reflux disease (GERD) experience persistent symptoms despite treatment with proton pump inhibitors (PPIs). These patients may have underlying dysmotility; therefore, targeting gastric motor dysfunction in addition to acid inhibition may represent a new therapeutic avenue. The aim o...