Diets including Animal Food Are Associated with Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is a clinical condition with a prevalence of up to 25% in Western countries. Typical GERD symptoms include heartburn and retrosternal regurgitation. Lifestyle modifications, including diet, are considered a first-line therapeutic approach. To evaluate the impact of life habits on GERD in this cross-sectional study, we used data collected through an online survey from 1146 participants. GERD was defined according to the Montreal Consensus. For all participants, clinical and lifestyle characteristics were recorded. Overall, 723 participants (63.1%) consumed a diet including animal food (non-vegans), and 423 participants (36.9%) were vegans. The prevalence of GERD was 11% (CI 95%, 9–14%) in non-vegans and 6% (CI 95%, 4–8%) in vegans. In the multivariate analysis, after adjusting for confounding factors, subjects on a non-vegan diet were associated with a two-fold increase in the prevalence of GERD compared to vegans (OR = 1.96, CI 95%, 1.22–3.17, p = 0.006). BMI and smoking habits were also significantly associated with GERD. This study shows that an animal food-based diet (meat, fish, poultry, dairy, and eggs) is associated with an increased risk of GERD compared to a vegan diet. These findings might inform the lifestyle management of patients with GERD-related symptoms

Comparison of Short- and Long-Term Effectiveness between Anti-TNF and Ustekinumab after Vedolizumab Failure as First-Line Therapy in Crohn's Disease: A Multi-Center Retrospective Cohort Study

BACKGROUND The effectiveness of anti-TNF or ustekinumab (UST) as a second-line biologic after vedolizumab (VDZ) failure has not yet been described. AIMS AND METHODS In this retrospective multicenter cohort study, We aim to investigate the effectiveness of anti-TNF and UST as second-line therapy in patients with Crohn's disease (CD) who failed VDZ as a first-line treatment. The primary outcome was clinical response at week 16-22. Secondary outcomes included the rates of clinical remission, steroid-free clinical remission, CRP normalization, and adverse events. RESULTS Fifty-nine patients who failed on VDZ as a first-line treatment for CD were included; 52.8% patients received anti-TNF and 47.2% UST as a second-line therapy. In initial period (Week 16-22), the clinical response and remission rate was similar between both groups: 61.2% vs. 68%, p = 0.8 and 48.3% vs. 56%, p = 0.8 on anti-TNF and UST therapy, respectively. Furthermore, in the maintenance period the rate was similar: 75% vs. 82.3%, p = 0.8 and 62.5% vs. 70.5%, p = 0.8, respectively. Of the patients, 12 out of the 59 stopped the therapy, without a significant difference between the two groups (p = 0.6). CONCLUSION Second-line biological therapy after VDZ failure therapy was effective in >60% of the patients with CD. No differences in effectiveness were detected between the use of anti-TNF and UST as a second line

Effectiveness of third-class biologic treatment in crohn’s disease : A multi-center retrospective cohort study

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn’s disease (CD) failing anti-Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD. Results: Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second-and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second-and VDZ as a third-class therapy (group B). At week 16–22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5). Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.Peer reviewe

Is acid relevant in the genesis of dyspeptic symptoms associated with nonerosive reflux disease?

Abstract: A consistent subset of patients with NERD suffers from symptoms centered in the upper part of the abdomen that are more characteristic of functional dyspepsia than reflux disease. The cause of this overlap is still unclear, but acid has been implicated as one of the possible common pathophysiological factors responsible for these two categories of upper gastrointestinal (GI) symptoms. Many physiological investigations and the modest success of proton pump inhibitors in resolving dyspeptic symptoms associated with typical reflux syndrome seem to support the concept that functional dyspepsia and NERD are two separate entities, which need to be treated with different drugs

Nocturnal reflux and sleep disturbances: an overlooked link in the past.

Commentary Gastro-oesophageal reflux disease (GORD) is highly prevalent in western countries. The main clinical manifestations are represented by heartburn and regurgitation and they are commonly used for the diagnosis of GORD, although their accuracy is far from optimal (1). The above symptoms can occur during the daytime and also throughout the nocturnal period. In the past, the progressively widespread use of 24-hour oesophageal pH-metry showed that the majority of reflux events belong to the post-prandial periods, while they are much less frequent during the nighttime (2). This temporal distribution of abnormal reflux episodes provided the rationale to explain, at least in part, the benefit of proton pump inhibitors (PPIs) in patients with GORD. In fact, these drugs are more effective during the daytime, when proton pumps are activated by fractioned meals, than through the nighttime, when their main pharmacological target does not work because of sleep (3). Despite the above findings, in the last decade we have witnessed a mounting evidence of the role of nighttime GORD in provoking a decreased quality of life, a variety of sleep disorders and diminished work performances (4). Several epidemiological surveys have confirmed that nocturnal reflux symptoms, in particular heartburn and regurgitation, can be reported by 2 out of 3 patients with GORD (5) and the relationship between GORD and sleep disorders has been recently established by many studies which have clearly demonstrated that 47%-57% of the GORD patients and approximately 25% of the US adult general population report having heartburn that awakens them from sleep during the night (6,7). Of the GORD patients, 63% report that they are unable to sleep well, 42% are unable to sleep during a full night, 39% have to take naps during the day and 34% have to sleep in a seated position because of nighttime heartburn (7). It has also been shown that sleep deprivation per se can adversely influence GORD, in that the inability to have a complete rest during the night is a potential mechanism for increasing the perception of symptoms in patients with GORD (8). Another important issue is the still poorly understood role of nocturnal reflux in determining extra-oesophageal and particularly respiratory symptoms because of the well-known longer-lasting duration and the slower clearing of supine refluxes compared with the daytime ones (9). Finally, the use of impedance-pH monitoring has shown that nocturnal weakly acidic reflux is as common as acid reflux in GORD patients (10) and a recent study has also proposed that this kind of nighttime reflux can sensitize oesophageal mucosa to the point to favor the occurrence of diurnal symptoms, such as sour or bitter taste in the mouth (11). The observational study performed in this field by French researchers (12) represents a further confirmation of the relevance of nocturnal reflux symptoms in the genesis of sleep disturbances leading to a reduced quality of life and work productivity on the day after. The strengths of the study consist in the high number of involved primary care physicians and the great sample of patients with nighttime GORD recruited by them. Nocturnal reflux symptoms were reported by 63,9% of the patients they analyzed and regular sleep disorders by 61,7% of them. These rates are quite similar to those already registered in previous epidemiological studies on this matter in western countries (4-7). In the study from Cadiot et al, multivariate statistical analysis demonstrated that nocturnal GORD symptoms, the age over 50 years and the use of hypnotic drugs were independent predictors of sleep disturbances. The last factor is of particular interest, because many doctors and patients ignore that drugs such as benzodiazepines, which are frequently taken by elderly people chronically and life-long, are associated with a slowing of gastric emptying and a reduction of lower oesophageal sphincter basal pressure, two of the main mechanisms favoring reflux events (8). The French Authors also showed that the control of GORD by administration of PPI therapy provoked a substantial decrease of nocturnal symptoms from 98,8% to 39,3% in patients reporting at least one nocturnal GORD symptom during the previous week and this was associated with the considerable improvement of other features pertaining to sleep disturbances. This is an important outcome of medical therapy of nighttime GORD, although the persistence of symptoms in about 40% of patients treated for 1 month with PPI therapy is a confirmation of the difficulty in blocking completely nocturnal reflux by the most powerful anti-secretory drugs at present used to cure GORD. In fact, they are more effective during the daytime than the nighttime as result of the activation of proton pumps by meals, unless we give them as double fractioned daily doses (3) or before dinner instead of before breakfast (13). Unfortunately, however, there is no mention of the dosing of PPIs, which were taken by almost all patients evaluated by Cadiot et al in their study. It must be acknowledged that the French investigation has other important limitations. Firstly, it has not been described whether the questionnaire the Authors used to collect symptom data was previously validated or was one of those already adopted for similar studies in the same field. It is well known that many of the questionnaires aimed at collecting subjective variables, such as symptoms, are questionable (14) and this is particularly true when changes of symptoms over time are monitored, as it was done before and one month after drug intake in patients with nocturnal symptoms who were recruited by the physicians coordinated by Cadiot et al. Secondly, PPI therapy was not only poorly defined in terms of dosage and timing of intake, but it is also evident that it was administered in uncontrolled manner. This represents a relevant bias in the interpretation of the results they obtained, even though the Authors themselves recognize that it would have been very difficult to organize a randomized, controlled trial in relation of the complex setting of the study. Thirdly, nocturnal cough cannot be considered with certainty as a reflux symptom, because it can be due to many causes and therefore needs to be substantiated by the use of more objective measurements. On the other hand, also typical reflux symptoms were defined in the study as GORD\u2013related exclusively on the basis of patients\u2019 perception and a more sound way to establish this relationship was lacking. Once again, this limitation is clearly due to large scale observational studies, which do not allow us to use more rigorous methods to show a firm link between symptoms and reflux events. In conclusion, this French research adds new fuel to the clinical relevance of an overlooked feature of reflux disease in the past, that is the important role of nocturnal reflux in inducing sleep disturbances and reduced work productivity on the day after. It is likely that we have to address more attention to nighttime GORD and to find additional drugs which are able to control it better than PPIs, which represent the first choice anti-reflux therapy today available. However, if the relationship between nocturnal reflux and sleep disturbances is established with great accuracy on the basis of instrumental methods, it is likely that patients with poor response to medical treatment can benefit from surgical fundoplication as further therapeutic option, even though data on the impact of this intervention on the improvement of sleep parameters related to nighttime reflux are very limited

The Relevance of Weakly Acidic Reflux in Patients With Barrett's Esophagus.

We read with great interest the paper by Krishnan et al1 on the factors predicting the persistence of intestinal metaplasia in patients with Barrett\u2019s esophagus before undergoing radiofrequency ablation (RFA). The authors found that uncontrolled, weakly acidic reflux is an important determinant of the incidence of persistent intestinal metaplasia in the distal esophagus, despite twice daily proton pump inhibitor (PPI) therapy before RFA. The advent of 24-hour esophageal pH impedance has allowed us to detect both acid and weakly acidic reflux, although the latter cannot necessarily be identified as a fluid containing bile salts. Moreover, it is well known that PPIs do not reduce the number of reflux episodes, but are only able to change acid into weakly acidic reflux. So, Krishnan et al documented a factor predicting the failure of RFA, but this is mainly the result of an ongoing, powerful, antisecretory therapeutic regimen taken by patients examined in their study instead of a welldefined pathophysiologic phenomenon. Using the same ambulatory pH-impedance technique, we have recently studied a group of patients with Barrett\u2019s esophagus off PPI therapy and showed that they have significantly greater acid and weakly acidic refluxes compared with patients with erosive esophagitis, nonerosive reflux disease, and control subjects. This means that patients with esophageal intestinal metaplasia have an increased reflux not only of acid, but also of weakly acid content independently of the intake of PPI therapy. This combined physiologic abnormality may be responsible for the formation of the esophageal metaplastic epithelium and perhaps for its persistence in those patients who do not benefit from RFA. In other words, also studying Barrett\u2019s patients off PPI therapy would have allowed Krishnan et al to find an uncontrolled weakly acidic reflux as the predictor of RFA failure without the interference of high-dosage PPI treatment, which determines a predominant reflux of this type. Moreover, the results of this study are further confirmation of the fact that weakly acidic reflux is able to induce not only the same symptoms of acid reflux, but is also associated with the same important esophageal histologic lesions, such as intestinal metaplasia, which characterizes patients with Barrett\u2019s esophagus. These findings reinforce the pathogenetic role of weakly acidic reflux in the generation of microscopic esophagitis, and metaplastic esophageal epithelium, and highlight the necessity of controlling this type of reflux to prevent the development of these histologic alterations. Thus, this investigation clearly claims for future studies aimed at testing whether stopping weakly acidic reflux by means of novel drugs or antireflux surgery may contribute to healing mucosal damage in Barrett\u2019s esophagus, or at least preventing RFA failure

The reason for failure of on-demand PPI therapy in NERD patients.

To The Editors: We read with interest the paper by Wu et al (1) showing that concomitant irritable bowel syndrome, in addition to functional dyspepsia, is associated with failure of on-demand Proton Pump Inhibitors (PPI) therapy in reflux patients. The Authors performed a large study in which all patients underwent conventional manometry and pH monitoring in order to be characterized. They included in the group with non-erosive reflux disease (NERD) patients with abnormal acid exposure and those with normal acid and a strong correlation between symptoms and acid reflux events (SI>75%). They classified patients with negative symptoms association as having functional heartburn (FH) and excluded them from the study. The separation of FH from NERD represents a very important point, because the former sub-group is likely to be associated more frequently with other functional GI disorders and this can influence the therapeutic PPIs response. Indeed, in a recent study (2), we have shown that sub-grouping the complex population of endoscopy-negative reflux patients by means of impedance-pH testing led us to demonstrate that several dyspeptic symptoms, such as those pertaining to the postprandial distress syndrome (3), overlap significantly more with FH than with NERD. This sustains the concept that FH may be part of functional GI disorders, in which other factors (i.e. visceral hypersensitivity, psychological factors, etc.) rather than acid seem to play a major role. Therefore, the response to PPI therapy, given in whatever modality in these patients, is very poor. However, the fact that NERD patients had higher failure rate of on-demand PPI therapy than those with Erosive Esophagitis (EE), even after Wu et al had excluded FH from their study, may depend on additional factors. For instance, the use of traditional pH-metry alone allowed the Authors to detect only NERD patients with an esophagus hypersensitive to acid, while those with a positive symptom association with weakly acidic reflux were necessarily missed. The modern impedance-pH technique has the merit to distinguish acid from weakly acidic reflux events and this allowed us to demonstrate that there is a subgroup of endoscopy-negative patients who have a clear association between heartburn and weakly acidic reflux episodes (4). The presence of patients pertaining to this last subgroup among those with NERD and normal acid in their esophagus represents one of the main causes of non response to PPIs (5) and could explain why in the above study the failure rate to these drugs was higher in NERD than in EE

The relevance of reflux monitoring off therapy.

To The Editors: We read the recent article by Vaezi MF. (1) with interest. The Author discussed on the opportunity to evaluate patients with symptoms suggestive of gastro-oesophageal reflux (GERD) by means of 24-h pH or impedance-pH monitoring On or Off therapy. He concluded that, after an empiric trial with twice-daily PPI therapy, in case of refractoriness, patients should undergo reflux monitoring On therapy in order to exclude reflux disease, while testing Off therapy has a limited value, because in this group it results only in an additional test proving what is already established by patients\u2019 lack of response to aggressive PPI therapy. We agree that an empiric treatment with a twice daily PPI trial is the correct initial approach to patients with suspected GERD and testing should be reserved only to those with persisting symptoms despite antisecretory drugs. However, we believe that a particular attention must be taken when considering the endoscopy-negative population. We have recently observed that patients with non-erosive reflux disease (NERD) evaluated using impedance-pH monitoring Off therapy (2) have frequently symptoms related to weakly acidic reflux, mainly in case of normal esophageal acid exposure. This appears a relevant point, in that we are now able to subtract this subgroup of patients with weakly acidic reflux disease from those without any reflux underlying their symptoms (functional heartburn, FH). These two subgroups require completely different therapeutic approaches (surgery or pain-modulators), although limited outcome data are available in this field (3,4). On the other hand, a recent study (4) has shown that NERD patients refractory to PPIs can equally respond to surgery. In the endoscopy-negative population the risk of including FH in NERD is rather high and we have shown that PPI therapy may cause an underestimation of GERD patients (inability to identify weakly acidic reflux patients) and an overestimation of FH patients (placebo effect) (5). These findings have been confirmed in a recent investigation, in which the analysis of PPIs response in a large number of endoscopy-negative patients with heartburn revealed that those patients with normal acid exposure and positive symptom association had a 50% response to PPIs (6). Therefore, we confirmed that the negative response to PPI therapy does not mean immediately that reflux can be excluded. Overall, in our opinion, impedance-pH testing On therapy is more indicated in patients with proven reflux disease (erosive esophagitis, Barrett\u2019s esophagus, previous abnormal pH-metry), while endoscopy-negative patients not responding to PPIs should be better assessed Off antisecretory therapy in order to be sure that they have GERD or not

The importance of subgrouping refractory NERD patients according to esophageal pH-impedance testing.

To The Editor: We read with great interest the paper by Frazzoni et al. (1) on the role of robot-assisted laparoscopic fundoplication in the treatment of PPI-refractory GERD patients as diagnosed by on-PPI impedance-pH monitoring. We must congratulate with the authors as they clearly demonstrated the efficacy of anti-reflux surgery in PPI-refractory GERD patients, including a long-term (3years) evaluation to reinforce their findings. They clearly showed that the major therapeutic gain of surgery relies on the reduction of weakly acidic reflux episodes, but we argue that some points of the study need to be discussed more in depth. The authors included in their analysis patients who underwent preoperative on-PPI impedance-pH testing revealing positive symptom association probability (SAP)/symptom index (SI), and/or abnormal oesophageal acid exposure time (AET), and/or abnormal number of total refluxes. Thanks to the clinical application of 24-hour oesophageal impedance-pH, we have previously proposed a subclassification of patients with typical reflux symptoms and normal upper gastrointestinal endoscopy into three different groups: (a) non-erosive reflux disease (NERD) pH-POS patients with normal endoscopy and abnormal distal AET; (b) hypersensitive oesophagus \u2013 patients with normal endoscopy, normal distal AET and positive symptom association for either acid or non-acid reflux; and (c) functional heartburn (FH) \u2013 patients with normal endoscopy, normal distal AET and negative symptom association for acid and non-acid reflux (2,3). It is not clear whether the authors have totally excluded from their analysis the subgroup of patients with FH, who represent about 25% of those having typical reflux symptoms without any kind of reflux underlying them. They cannot anymore considered within the realm of GERD according to Rome III criteria (4,5) and frequently do not respond to PPIs. It is also obvious that they cannot benefit from surgical anti-reflux therapy. Since the introduction of impedance-pH monitoring in clinical practice, different normal values have been proposed in order to diagnose GERD. The most common used [i.e. the United States (US), Belgian-French (BF) and Italian (ITA) normal values] have different upper limits of normality for distal AET (USA=6.3%, BF=6.2% and ITA=4.2%, respectively) and total number of reflux episodes (USA=73/daily, BF=72/daily and ITA=54/daily, respectively), the two main parameters used to distinguish normal from abnormal GER (6-8). Moreover, a recent paper by Zerbib et al (9) modified the French impedance normal values reducing their upper limit of normality for total reflux episodes to 53 that was almost the same value we proposed several years before (8). In their study, Frazzoni et al. applied normal values that are significantly lower than those mentioned before (AET=3.3%; total number of reflux episodes=45). Given these lower limits of normality, one can hypothesize that some patients have been enrolled and treated despite the presence of a mild or border-line disease, with the risk of weaken the very good outcomes obtained among their PPI-refractory GERD patients. Therefore, we believe that indicating the number and intensity of symptoms reported by their patients during the testing day could be useful in order to justify the choice of a surgical approach and to corroborate the strength of their findings in terms of post-surgical outcome. Whereas the diagnostic utility of impedance-pH monitoring in diagnosing GERD in both patients on- and off-PPI therapy have been extensively demonstrated in several recent studies (10-14), very scant data are available on the real clinical impact of this novel technique in GERD management (15). This is particular true for patients with NERD and normal esophageal acid exposure with positive symptom association to acid and/or non-acid reflux who are characterized by an \u201chypersensitive esophagus\u201d and represent about half of the NERD patients and 1/3 of the entire GERD population (16). To date, these patients are considered a very difficult task for both gastroenterologists and surgeons in terms of management and treatment, since no effective drugs are available in our pharmacological armamentarium (i.e. PPI and H2 antagonists as well as antacids are not effective in these patients). Thus, we think that the Authors, demonstrating the very good efficacy of anti-reflux surgery in patients with positive symptoms association (64%) and without history of esophagitis (50%), had the remarkable opportunity to emphasize this concept and highlight that an excellent therapeutic chance for this large group of patients actually exists and should be strongly considered, although further studies are necessary to confirm these findings. Moreover, the Authors compared the results of impedance-pH testing performed before and after robot-assisted laparoscopic fundoplication without discussing the fact that the patients were on PPI drugs during the first examination and their results could have been different if the preoperative impedance-pH was done in patients not taking any antisecretory compounds. In fact, it is well known that PPI therapy does not reduce the number of total reflux episodes, but changes the chemical nature of refluxate which becomes predominantly weakly acidic from acid. We are aware that surgical therapy enables to block both acid and weakly acidic refluxes and this certainly affected the positive results obtained by Frazzoni et al (1) on the prevalent control of weakly acidic reflux episodes. We think that it is not fair to compare functional tests on PPIs before and off PPIs after surgery. In conclusion, we believe that this is a very interesting study showing the benefit of surgical therapy in controlling mainly weakly acidic refluxes of patients not responding to PPIs; however, a better characterization of the study population and a more in depth discussion of the main findings would have been useful for the reader

Esophageal acid exposure still plays a major role in patients with NERD.

To The Editor: We read with great interest the paper by Zhong et al (1) on the significant correlation between esophageal intraluminal baseline impedance and the severity of acid reflux as well as esophageal mucosal histopathological changes, such as dilated intercellular spaces (ICS) and tight junction alterations. This means that low baseline impedance values reflect microscopic mucosal inflammatory abnormalities, which are mainly induced by acid and increase across the spectrum of GERD. In particular, the Chinese study reports that the mean baseline impedance values in non-erosive reflux disease (NERD) were significantly lower than in controls and, among NERD subgroups, the lowest levels pertained to patients with increased acid reflux events and those with mixed acid/weakly acidic reflux episodes. Analyzing the results more in depth, one can realize that an important information is lacking. In fact, patients with NERD were classified into 4 groups on the basis of normal/abnormal number of reflux episodes (i.e. acid, weakly acidic, mixed acid and weakly acidic, alkaline) without mentioning anything about the level of esophageal acid exposure in them. Previous studies documented that about 40% of NERD patients have abnormal distal esophageal acid exposure time (AET) (2-5). For instance, Martinez et al. reported that 45% of their NERD patients had an increased AET (3), while we observed a rate ranging from 33% to 42% of abnormal AET in large samples of endoscopy-negative patients (2,4,5). Moreover, it has been shown that both patients with abnormal number of weakly acidic or mixed reflux events and those with normal number of acid reflux episodes may have also abnormal AET (6,7). Thus, classifying patients only on the basis of the number of reflux episodes without considering the presence of a normal/abnormal AET may lead to an underestimation or overestimation of the role of acid in these patients. Moreover, this could represent a potential confounding factor for the evaluation of baseline impedance values in both weakly acidic and mixed reflux subgroups, thus questioning the conclusion that also weakly acidic reflux decreases baseline impedance values in NERD patients. It must be also stressed that the number of patients with abnormal number of weakly acidic reflux events is much higher than expected. In fact, the increase in weakly acidic reflux may be the result of PPI therapy (8) and we wonder whether the withdrawal of these drugs had been done for a period long enough to guarantee that impedance-pH testing was not affected by the above treatment. Anyway, the results obtained in this study cannot be easily extrapolated to those we can find in populations of Western countries. Finally, it is very surprising that the authors acknowledged the use of light microscopy (LM) instead of transmission electron microscopy (TEM) as an important limitation of their study. In fact, we have shown that LM is able to demonstrate with very good accuracy all the histopathological alterations characterizing microscopic esophagitis, including the ICS (9,10). This method is not only easier and cheaper than TEM, but also more practical as it can be used routinely during the daily clinical practice. An expert pathologist permits to exploit on biopsy samples the entire diagnostic information contained in each element proper of esophageal microscopic inflammation and, if it is true that finding low baseline impedance values is expression of subtle inflammatory mucosal changes, a good correlation between this new functional marker and the damage of esophageal mucosa would be better found by using LM rather than TEM