Anti-quenching NIR-II molecular fluorophores for in vivo high-contrast imaging and pH sensing.

The contrast and sensitivity of in vivo fluorescence imaging has been revolutionized by molecular fluorophores operating in the second near-infrared window (NIR-II; 1000-1700 nm), but an ongoing challenge is the solvatochromism-caused quenching in aqueous solution for the long-wavelength absorbing fluorophores. Herein, we develop a series of anti-quenching pentamethine cyanine fluorophores that significantly overcome the severe solvatochromism, thus affording stable absorption/emission beyond 1000 nm with up to ~ 44-fold enhanced brightness and superior photostability in aqueous solution. These advantages allow for deep optical penetration (8 mm) as well as high-contrast and highly-stable lymphatic imaging superior to clinical-approved indocyanine green. Additionally, these fluorophores exhibit pH-responsive fluorescence, allowing for noninvasive ratiometric fluorescence imaging and quantification of gastric pH in vivo. The results demonstrate reliable accuracy in tissue as deep as 4 mm, comparable to standard pH electrode method. This work unlocks the potential of anti-quenching pentamethine cyanines for NIR-II biological applications.

Large Buffering Effect of the Duodenal Bulb in Duodenal Switch: a Wireless pH-Metric Study.

INTRODUCTION: Bariatric procedures result in massive weight loss, however, not without side effects. Gastric acid is known to cause marginal ulcers, situated in the small bowel just distal to the upper anastomosis. We have used the wireless BRAVO™ system to study the buffering effect of the duodenal bulb in duodenal switch (DS), a procedure in which the gastric sleeve produces a substantial amount of acid. METHODS: We placed a pre- and a postpyloric pH capsule in 15 DS-patients (seven men, 44 years, BMI 33) under endoscopic guidance and verified the correct location by fluoroscopy. Patients were asked to eat and drink at their leisure, and to register their meals for the next 24 h. RESULTS: All capsules but one could be successfully placed, without complications. Total registration time was 17.2 (1.3-24) hours prepyloric and 23.1 (1.2-24) hours postpyloric, with a corresponding pH of 2.66 (1.74-5.81) and 5.79 (4.75-7.58), p < 0.01. The difference in pH between the two locations was reduced from 3.55 before meals to 1.82 during meals, p < 0.01. Percentage of time with pH < 4 was 70.0 (19.9-92.0) and 13.0 (0.0-34.6) pre and postpylorically, demonstrating a large buffering effect. CONCLUSION: By this wireless pH-metric technique, we could demonstrate that the duodenal bulb had a large buffering effect, thus counteracting the large amount of gastric acid passing into the small bowel after duodenal switch. This physiologic effect could explain the low incidence of stomal ulcers.

Short-segment and intrasphincteric gastroesophageal reflux.

PURPOSE OF REVIEW: The traditional gold standard for measuring gastroesophageal acid reflux has been by placing a pH sensor 5 cm proximal to the lower esophageal sphincter. It is known that damage induced by reflux is maximal near to the gastroesophageal junction and this has stimulated interest in determining acid reflux at that site. RECENT FINDINGS: The extent of esophageal exposure from refluxing gastric acid is inversely related to the distance proximal to the gastroesophageal junction. In addition, the pH transition point from gastric to esophageal pH can be displaced proximally within the lower esophageal sphincter without complete loss of sphincter tone. This intrasphincteric reflux is associated with proximal extension of cardia mucosa because of columnar metaplasia of the most distal esophageal squamous mucosa. SUMMARY: The most distal esophageal mucosa is exposed to substantially greater gastric acid refluxate than that recorded at the traditional site 5 cm proximal to the lower esophageal sphincter.

Evaluation of Gastroesophageal Reflux by Combined Multichannel Intraluminal Impedance and pH Monitoring and Esophageal Motility Patterns in Children with Esophageal Atresia.

Background Gastroesophageal reflux disease (GERD) and esophageal dysmotility are common in patients with esophageal atresia (EA). The aim of this study was to evaluate GERD and esophageal motility patterns in children with EA using combined multichannel intraluminal impedance and pH (MII-pH) monitoring and high-resolution esophageal manometry (HREM), respectively. The reflux patterns seen in EA patients were also compared with a control group of normal children with suspected GERD. Methods A retrospective chart review was done on 35 patients with EA and 35 age- and sex-matched normal controls with suspected GERD, who had undergone 24-hour MII-pH monitoring. Impedance data were compared between both cohorts. Eight of the EA patients also underwent HREM. Results In the EA cohort, the median age was 53 months, with 21 males, and 71.4% had Type C EA. A total of 85.7% of the EA cohort and 40% of the control group were on proton-pump inhibitor (PPI) therapy during the MII-pH study. There was no significant difference in the total retrograde bolus movements (RBMs) between the EA cohort (1,457) and the control group (1,482). Acidic RBMs was significantly lower in the EA group (208) compared with the control group (689), p = 0.0008. Nonacid reflux index (NARI) was significantly higher in EA children (1.1; 0.0-7.8) compared with controls (0.6; 0.0-5.7), p = 0.0046. In EA patients, only 335/1,183 (28%) total symptom occurrences were associated with RBM. The mean distal baseline impedance (DBI) was significantly lower in EA (1,029.6 [410.9 SD] Ω) compared with controls (2,998.2 [1028.8 SD] Ω) with suspected GERD, p < 0.0001. By logistic regression, only PPI use had a significant effect on DBI, p < 0.0001. HREM was abnormal in all eight EA patients. Four out of eight EA patients had a different peristaltic pattern for their solid swallows compared with their liquid swallows in HREM. Conclusions MII-pH testing allowed increased detection of nonacid reflux events in EA patients, which would have been missed with standard pH monitoring alone. NARI was the only reflux parameter which was significantly higher in the EA cohort compared with the control group with suspected GERD. Majority (72%) of symptoms in EA patients were not temporally related to RBM in MII-pH testing. DBI was significantly lower in EA patients compared with controls. Esophageal motility by HREM was abnormal in all EA patients.

Long segments of columnar-lined lower esophagus are not always metaplastic

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The presence of columnar epithelium in the esophagus is associated with two conditions: Barrett’s esophagus and heterotopic gastric mucosa. The former results from the metaplastic replacement of the normal distal squamous esophageal lining, is associated with gastroesophageal reflux and is a pre-neoplastic condition. The second is thought as a congenital condition, resulting from the incomplete squamous epithelialization of the esophagus during embryologic development. It is found mainly in the cervical esophagus. Histologically, Barrett’s esophagus is composed of an admixture of cardiac mucosa, oxintocardiac mucosa and intestinal metaplasia. Most of heterotopic gastric mucosa consists of oxyntic mucosa where the mucosal glands are straight and composed of parietal and chief cells. There are few reports of heterotopic gastric mucosa in the lower esophagus, generally presenting as small islands. In the present report, a series of four cases of large lower esophageal heterotopic gastric mucosa is described. All patients were initially misdiagnosed with Barrett’s esophagus and referred for surveillance. The correct diagnosis was based in endoscopic and histological features. In all, a circular tiny strip of squamous mucosa was observed at endoscopy between the lower end of the columnarlined esophagus and the esophagogastric junction, defined as the proximal end of the gastric folds. Biopsy samples taken from the columnar-lined segments of the four patients showed pure oxyntic mucosa. When columnar-lined esophagus is observed in the distal esophagus not in continuity with gastric mucosa, the diagnosis of heterotopic gastric mucosa must be thought and confirmed histologically by the presence of pure oxyntic mucosa

[Influence of chest physiotherapy on gastro-œsophageal reflux in children]. / Influence de la kinésithérapie respiratoire sur le reflux gastro-œsophagien chez l'enfant.

INTRODUCTION: Chest physiotherapy is regularly prescribed for children, particularly in cystic fibrosis. Gastro-oesophageal reflux is common in this disease and is associated with certain chest physiotherapy manoeuvres. AIM OF THE STUDY: To evaluate the influence of two chest physiotherapy techniques on gastro-oesophageal reflux in children. MATERIAL AND METHOD: Twenty-nine children were investigated by routine pHmetry. During the examination, they performed two chest physiotherapy manoeuvres in a seated position for 10 minutes each with a 5 minutes rest between them. The two manoeuvres used were a slow expiration technique (ELPr) and positive expiratory pressure (PEP). It was a prospective study and the order of manoeuvres was randomised. The pH traces were analysed blindly when all the studies had been completed. RESULTS: In the sample, 21% of children had gastro-oesophageal reflux during the physiotherapy session. No relationship was found between reflux during physiotherapy and pathological reflux (P=0.411) nor the physiotherapy technique used (P=0.219). CONCLUSION: The use of these two chest physiotherapy techniques in children in a seated position can produce gastro-oesophageal reflux.

The use of SmartPill for gastric monitoring.

Testing to define delayed gastric emptying is required to diagnose gastroparesis; rapid emptying is found in other patients. Commonly performed methods of gastric emptying testing include scintigraphy and breath testing. The SmartPill wireless motility capsule (WMC) system is US FDA-approved for evaluating suspected delayed emptying in gastroparesis and functional dyspepsia. The device measures transit in the stomach, small intestine, and colon by detecting characteristic pH transitions; and quantifies pressure waves in each gut region. WMC gastric emptying times correlate with scintigraphic measures. Incremental benefits of WMC testing in patients with suspected gastroparesis include delineation of pressure abnormalities and small intestinal and colonic transit delays. Acceptance of trial data confirming usefulness of WMC testing in suspected gastric motor disorders has been hampered by small sample sizes and design limitations. Ongoing multicenter studies will validate the utility of WMC methods in patients with suspected gastroparesis and other upper gastrointestinal motor disorders.

Can multichannel intraluminal pH-impedance monitoring be limited to 3 hours? Comparison between ambulatory 24-hour and post-prandial 3-hour recording.

Esophageal multichannel intraluminal pH-impedance recording (MII) is now a valid technique for determining the acidic, liquid, gas or mixed nature of gastroesophageal reflux episodes. However, some recordings may stop prematurely due to technical reasons or poor patient tolerance of the probe. Therefore, we questioned whether analysis of post-prandial 3-hour recording could predict the results obtained in ambulatory 24-hour recording. Fifty patients with symptoms of gastroesophageal reflux disease were investigated. For each patient, post-prandial 3-hour MII was recorded after a test meal, then followed by ambulatory 21-hour MII. Correlation between the total number of liquid reflux events in the 3-hour and 24-hour recordings was elevated (R=0.71; P<0.001), with better correlation for acid (R=0.80; P<0.001) and weak acid reflux (R=0.56; P<0.001) than non-acid reflux (R=0.44; P<0.01). Sensitivity and specificity of 3-hour recording in detecting elevated liquid reflux over 24 hours (id>75reflux/24 h) were 49% and 100%, respectively, for 8 or less liquid/mixed reflux events per 3 hours, and 78% and 88%, respectively for 15 or more liquid/mixed reflux events per 3 hours. The sensitivity and specificity of symptom association probability (SAP) calculated over 3 hours were 56% and 91%, respectively. In conclusion, we identified relevant indicators on the 3-hour post-prandial recording likely to give accurate prediction of absence or presence of gastroesophageal reflux disease from 24-hour MII recording.

The effect of a hay grid feeder on feed consumption and measurement of the gastric pH using an intragastric electrode device in horses: a preliminary report.

REASONS FOR PERFORMING STUDY: Obesity and gastric ulceration are highly prevalent in horses. Management modifications for preventing squamous gastric ulceration include frequent feeding and free access to pasture; however, these practices may predispose horses to obesity. OBJECTIVES: To compare the percentage of hay consumed, intragastric pH and horse activity between feeding from the ground and a hay grid feeder. STUDY DESIGN: Crossover experimental study. METHODS: A pH electrode was inserted into the stomach to record the intragastric pH for 48 h. Horses received 1% of their body weight in grass hay twice a day. Horses were assigned to be fed from the ground or a commercial hay grid feeder for 24 h and then switched to the opposite protocol for an additional 24 h. Horses were continuously video-recorded and the percentage of time spent eating or drinking, walking or standing, and lying down were calculated. Two point data were compared by paired t test and pH over time was compared by repeated measures ANOVA. RESULTS: Horses consumed significantly greater amounts of grass hay when fed on the ground compared with a hay grid feeder (n = 9; P<0.001). There were no significant differences between the groups for mean intragastric pH values (n = 6; P = 0.97), mean intragastric pH over time (n = 6; P = 0.45) the length of time the pH was below 4.0 (n = 6; P = 0.54), and the percentage of time horses spent eating or drinking (n = 9; P = 0.52), walking or standing (n = 9; P = 0.3), or lying down (n = 9; P = 0.4). Within each group horses spent more time eating during the day compared with the night (n = 9; hay grid feeder P = 0.003; ground feeding P = 0.007). CONCLUSIONS: The hay grid feeder studied may be used to reduce the amount of hay ingested by horses without reducing the time horses spend eating.

Intragastric acidity during the first day following administration of low-dose proton pump inhibitors: a randomized crossover study.

OBJECTIVE: Low-dose proton pump inhibitors (PPIs) are often administrated as maintenance therapy for gastroesophageal reflux disease (GERD) and on-demand PPI therapy is a viable option for long-term management of GERD. The aim of this study is to investigate intragastric acidity during the first day following the administration of low-dose PPIs. SUBJECTS AND METHODS: The study employed a crossover design. The subjects were 10 healthy volunteers who were administrated lansoprazole 15 mg (orally disintegrating) or rabeprazole 10mg. All subjects underwent pH monitoring with a wireless system during the first day after PPI administration. RESULTS: There was no significant difference in the average intragastric pH during the first day of administration of lansoprazole and rabeprazole (3.3±1.1 vs. 3.2±0.7, paired t test), although the pH was significantly higher with both drugs as compared with the baseline (1.8±0.4, P<0.01). The pH 4 holding time ratio during the first day showed no significant difference between lansoprazole and rabeprazole (35.2±22.4% vs. 34.3±15.0%), and was also significantly higher than at baseline (0.35±1.73%, P<0.01). The two PPIs differed with respect to the peak of the pH 4 holding time ratio. CONCLUSIONS: Lansoprazole 15 mg and rabeprazole 10 mg showed sufficient inhibition of intragastric acidity during the first day after PPI administration and the effects did not differ between drugs, although there was a difference in their time at which the peak effects were reached.

Traditional vs wireless intragastric pH monitoring: are the two techniques comparable?

BACKGROUND: Few data are available comparing intragastric pH measured with the traditional catheter-based and the more recent wireless system (Bravo), and also comparing intraesophageal and intragastric pH during reflux events. Aims of our study were to elucidate these points. METHODS: Eleven subjects with functional dyspepsia underwent placement of a Bravo capsule 9 cm below the squamo-columnar junction (SCJ) and of a dual-electrode catheter, so that the distal electrode was located 9 cm below and the proximal one 6 cm above the SCJ. KEY RESULTS: The wireless system showed lower intragastric pH than the traditional catheter in the postprandial period (median 2.2 wireless vs 2.7 catheter, P < 0.05) but not in the whole 24 h. Moreover, during the 24 h, minimum intraesophageal pH during reflux events was lower than the simultaneous pH in the gastric body recorded using the catheter (2.2 vs 2.4, P < 0.01) and in the postprandial period lower than the one recorded using both techniques (2.3 vs 2.8 wireless and 3.2 catheter, P < 0.001). CONCLUSIONS & INFERENCES: (i) after meals, in the 1st 2 h postprandial pH in the gastric body is significantly lower when measured with the wireless capsule than with the traditional catheter, presumably because of less buffering by food in proximity of the mucosa, (ii) during reflux events intraesophageal pH is lower than pH in the gastric body, in accordance with the notion of greater intragastric acidity in the subcardial region.

Comparison of continuous pH-meter and intermittent pH paper monitoring of gastric pH in critically ill children.

OBJECTIVE: A gastric pH below 4 increases the risk of gastrointestinal hemorrhage in critically ill patients. The pH can be monitored intermittently by testing the gastric aspirate using pH paper or continuously using a pH-meter (often in combination with multichannel intraluminal impedance). The objective of this study was to compare these two methods of pH measurement. METHODS: An observational, prospective study was conducted in critically ill children between 1 month and 14 years with at least two risk factors for gastrointestinal hemorrhage. Gastric pH was measured continuously by a multichannel pH-meter tube and every 2 h using pH paper on aspirates of gastric juice. RESULTS: A total of 471 gastric pH measurements were analyzed. The mean gastric pH measured by the pH-meter was 4.3±2.5 and that by pH paper was 3.9±2.2. The gastric pH was above 4 in 49.6% of the measurements taken on the basis of the gastric aspirate and in 49.8% of the pH-meter readings. The correlation between the two methods was moderate (0.59; P<0.001) but the concordance was low (0.54). The concordance with regard to determining a gastric pH above or below 4 was 77%. CONCLUSION: pH paper is a simple and inexpensive method that can be useful for initial patient monitoring, but it should not be used as a substitute for monitoring by pH-meter in patients in whom strict control of the gastric pH is required.

Acid and weakly acid gastroesophageal refluxes and type of respiratory symptoms in children.

OBJECTIVES: To evaluate the association between the frequency of acid reflux (AR) and weakly acid reflux (WAR) and specific respiratory symptoms (RS) in childhood. STUDY DESIGN: We retrospectively reviewed medical records of children with difficult-to-treat RS, not under acid suppressive therapy, and with a positive multiple intraluminal esophageal impedance (pH/MII) monitoring. To discriminate children with prevalent AR and WAR events, a ROC curve was designed and the distribution of the different RS in children with prevalent AR or WAR events was analyzed. RESULTS: A higher number of AR over WAR events was detected (p < 0.0001) but the WAR-to-AR events ratio progressively decreased with the age of the subjects (p < 0.01). Similar total number of reflux events was found in the three age group and in children with a more prevalent WAR or AR. The most prevalent RS, equally distributed among the three age groups, were persistent and/or nocturnal cough, wheezy bronchitis/asthma, and recurrent lower respiratory tract infections (RLRTI). Apnoea was most frequent in infants (p = 0.036). A higher frequency of RLRTI, but not of nocturnal cough or wheezy bronchitis/asthma, was shown in WAR as compared with AR patients (p = 0.040), and specifically those in the school-aged group (p = 0.013). Age and WAR were respectively identified as independent predictors of apnoea and RLRTI (p < 0.05). CONCLUSION: WAR events are common in children with gastroesophageal reflux and difficult-to-treat RS and often associated with RLRTI. These findings support the role of pH/MII monitoring in the evaluation of these patients and may explain the disappointing clinical results often observed with anti-acid treatments.

Combined lung-sound and reflux-monitoring: a pilot study of a novel approach to detect nocturnal respiratory symptoms in gastro-oesophageal reflux disease.

BACKGROUND: Increased prevalence of respiratory symptoms has been commonly reported in patients with gastro-oesophageal reflux disease (GERD). AIM: To introduce a novel Lung-Sound-Monitoring device that allows simultaneous measurement of both nocturnal respiratory symptoms and episodes of acidic and biliary refluxes. METHODS: Nocturnal respiratory symptoms (coughing and wheezing) were continuously recorded in 20 healthy subjects and 30 reflux patients with respiratory symptoms in parallel to combined pH-monitoring and Bilitec measurement. RESULTS: Analysis could be completed in 20 healthy subjects and in 25 patients with reflux. A clear temporal correlation to reflux phases was detected in 49% of coughing and 41% of wheezing events, respectively. Moreover, 89% of the coughing and 100% of the wheezing events succeeded reflux episodes. Finally, the technique was capable of assessing a statistically significant difference between patients and controls regarding the occurrence of these symptoms. CONCLUSIONS: Our pilot study establishes the Lung-Sound-Monitoring system as a unique tool to measure objectively the temporal correlation between gastroesophageal reflux and the appearance of respiratory symptoms. It represents a useful technique to identify patients with respiratory symptoms due to reflux, and therefore allows one to determine and quantify the impact of therapeutic interventions such as antireflux therapy on respiratory symptoms.

Effective administration method of intravenous proton pump inhibitor: a novel testing using a BRAVO catheterless pH monitoring system.

BACKGROUND/AIMS: This study investigated the use of the BRAVO catheterless pH monitoring system to determine the effective administration method of intravenous proton pump inhibitor and the effectiveness of 80 mg pantoprazole per day on the regulation of gastric acid. METHODS: A total of 32 patients who underwent endoscopic resection were randomly assigned to the repeated bolus injections group (40 mg dose, twice per day) and continuous infusion group (mixed with 5% glucose, continuous infusion of 80 mg per day). Then, pantoprazole was administered and intragastric pH was measured for 48 hours through a BRAVO capsule. The length of time until the intragastric pH reached 4 and 6 after administration was measured, as well as the mean/median pH for 48 hours and the fraction times (%) of pH >4 and >6 for 48 hours. The factors affecting intragastric pH were also analyzed. RESULTS: There were no complications due to the attachment of the BRAVO capsule. No significant differences according to administration methods were found in all factors. Only Helicobacter pylori had significant effect on the fraction times (%) of pH >4 and >6 for 48 hours (p<0.05). CONCLUSIONS: The effects of intravenous proton pump inhibitor were similar between the administration methods. Therefore, the repeated bolus injection method, which is relatively simple, is a good choice. Regarding the dose of intravenous pantoprazole, which is used after successful endoscopic hemostasis, 80 mg would be sufficient. We hope that this study encourages the use of the BRAVO catheterless pH monitoring system.

[Nocturnal long-term monitoring of lung sounds in patients with gastro-oesophageal reflux disease]. / Nächtliche Langzeitregistrierung von Lungengeräuschen bei Patienten mit gastroösophagealem Reflux.

Gastro-oesophageal reflux disease (GERD) is one of the most common clinical conditions in the developed countries. Particular interest in pulmonary manifestations of this disease has arisen over the last few years. Although the high coincidence between reflux and chronic cough is unquestioned, the proof of a causal correlation is still lacking. In this paper we present the Marburger Lung-Sound-Monitoring as a new method for the detection of nocturnal respiratory symptoms such as cough, wheezing and throat clearing and their temporal correlation with reflux. This method will in future allow us to precisely record and to evaluate the extent and duration of reflux events and their correlation with respiratory symptoms.

[Clinical and instrumental characteristics of the gastroesophageal reflux in children with bronchial asthma, possibilities of therapy].

The group of 141 school-year children with bronchial asthma was examined. The condition of upper gastrointestinal tract was assessed. Gastroesophageal reflux disease was revealed in 94 children (66.7%). Dyspepsia, mucosal damage and changes of 24-hour pH monitoring data were more intensive in acute period of asthma and in children with severe asthma. Acid supression in the complex therapy of gastroesophageal reflux disease permited to minimise symptoms of dyspepsia and improve the pH monitoring data.

[Peculiarities of acid production in gastric ulcer type I and II].

The literature data are presented on the nature and characteristics of acid-production on gastric ulcer disease. Functional status and gastric acid-production indicators related to duration of ulcer disease, especially its clinical course, the nature of complications. The advantage as aspiration probe method, and stomach pH-metry were shown. Indicators of stomach acid-production should be taken into account when determining the surgical tactics and choice of intervention method for ulcer disease.