The authors would like to thank Restech for providing an educational grant.

The following study protocol was reviewed and approved by the Ethics Committee of the Medical Faculty of the University of Cologne.
NOTE: Ensure that the patient arrives NPO for the following gastrointestinal function testing. Perform a high-resolution manometry to determine the exact location of the lower esophageal sphincter (LES) and to rule out esophageal dysmotility disorders such as achalasia. The patient should be off antisecretory medication for at least 7 days prior to ensure a valid pH measurement.
1. Setting up the esophageal pH monitoring system
<ol>
	<li>Insert batteries into the esophageal monitoring system.</li>
	<li>Connect the esophageal pH catheter to the device.</li>
	<li>Start the device. Make sure date and time is accurate. Select Start study.</li>
	<li>Calibrate the catheter in solutions with pH 4 and 7 and rinse the probe in water. Set the probe aside for insertion.</li>
</ol>
2. Setting up laryngopharyngeal pH monitoring system by first formatting the SD card with patient&#8217;s data.
<ol>
	<li>Insert the SD card into the computer and open the software for laryngopharyngeal pH monitoring (e.g., DataView 4). Add a new patient by clicking on New and typing in all details about the patient. Click Save to save the data to the SD card. Eject the SD card and insert it into the recorder.</li>
	<li>Insert batteries into the transmitter using the supplied screwdriver to remove the cover of the transmitter case and install a new CR1632 lithium coin battery.</li>
	<li>Insert two AA batteries into the recorder.</li>
	<li>Turn the recorder on. Use the up/down keys to select Setup. Press any round key to select the Setup mode. Modify the time and date if needed by using the up/down keys to change the digits and any round key to select the respective value. If time and date is correct, select Yes and continue.</li>
	<li>Select No when the Recorder asks &#8220;Tst PSG Adapter?&#8221;.</li>
	<li>Select Study in the main menu.</li>
	<li>The transmitter is now detected automatically. Confirm that the correct transmitter is detected and press any round key for confirmation. The transmitter displays the serial number that is paired with the recorder.</li>
	<li>Attach the probe to the transmitter. 
	NOTE: When connected to the transmitter, the red light-emitting diode (LED) at the probe tip will flash once per second. The LED stops flashing after four hours to conserve battery life.</li>
	<li>Select Hydrate for the calibration process. Hydrate the probe with the provided clear water solution by placing the probe tip in the clear water solution and agitating briefly. Press any round key to start the hydration process. 
	NOTE: The Recorder will display &#8220;Hydrating&#8221; and will count down from &#8220;300 seconds&#8221; to zero or will transition to 15 seconds countdown when the recorder detects that the probe is hydrated. Set the probe aside for insertion.</li>
</ol>
3. Placing the esophageal pH catheter first
<ol>
	<li>Ensure that the patient is sitting upright, looks straight and swallows periodically. Provide a small glass of water with a straw to assist swallowing.</li>
	<li>Ask the patient which side of their nose is clearer and easier to breathe through.</li>
	<li>Apply a topical gel that contains a local anesthetic to the probe shaft for ease of insertion.</li>
	<li>Insert the Probe through the patient&#8217;s nose, straight in and not up. A measuring scale on the probe shaft helps to determine the correct position. 
	NOTE: The correct position is 5 cm above the LES as previously determined by high resolution manometry.</li>
</ol>
4. Securing the esophageal pH catheter
<ol>
	<li>Secure the probe as closely to the nares as possible to ensure that it does not move during the study using surgical tape.</li>
	<li>Attach the probe to the cheek, near the nose.</li>
	<li>Loop the probe over the ear and use tape to affix the probe to the neck, behind and below the ear.</li>
</ol>
5. Placing the laryngopharyngeal pH catheter
<ol>
	<li>Ensure that the patient is sitting upright, looks straight and swallows periodically.</li>
	<li>Apply a topical gel that contains a local anesthetic to the distal end of the probe shaft for ease of insertion. 
	Caution: DO NOT apply topical gel to the probe tip where the sensor is located.</li>
	<li>Insert the probe through the patient&#8217;s opposite nostril of the esophageal catheter, straight posteriorly and not up. 
	NOTE: The round probe tip will help it curve around and through the velopharyngeal port into the oropharynx. The distance from the patient&#8217;s nares to the oropharynx can often be estimated by using the distance from the nares to the earlobe.</li>
	<li>Confirm that the red light is clearly visible, lateral to or slightly below the uvula. Use a tongue depressor for clear visibility if needed. 
	NOTE: If the patient&#8217;s gag reflex is triggered, retract the probe to a higher position in the oropharynx.</li>
</ol>
6. Securing the probe and transmitter
<ol>
	<li>Secure the probe as closely to the nares as possible to ensure that it does not move during the study using surgical tape.</li>
	<li>Attach the probe to the cheek, near the nose.</li>
	<li>Loop the probe over the ear and use tape to affix the probe to the neck, behind and below the ear.</li>
	<li>Attach the transmitter to the patient&#8217;s clothing with the clip-on transmitter carrying case.</li>
</ol>
7. Ensuring that simultaneous pH measurements are performed
<ol>
	<li>Make sure the internal clocks of both pH measurement devices are synchronized. Manually adjust the times if needed.</li>
	<li>Start esophageal and laryngopharyngeal pH studies concurrently. Select a 24-hour study for the laryngopharyngeal pH measuring device.</li>
</ol>
8. Patient diary and instructions
<ol>
	<li>Ask the patient to fill out a detailed diary that includes mealtimes, exact time of supine periods and symptoms they experience during the time of the study.</li>
	<li>Provide the following instructions for the 24-hour measurement period to the patient to ensure a successful data recording: 
	Three mealtimes on day 1 of the study, one mealtime on day 2 of the study. 
	No supine periods before 9pm. 
	Eat, drink, and behave as usual (daily activities can be done). 
	Caution: Devices are NOT waterproof.</li>
</ol>
9. Removing the esophageal and laryngopharyngeal probe after the 24-hour study period is completed
<ol>
	<li>Concurrently end the study on both devices.
	<ol>
		<li>End the esophageal pH study by pressing the two buttons located in the middle simultaneously until &#8220;upload later&#8221; appears on the display.</li>
		<li>End the laryngopharyngeal pH study by simultaneously pressing the cough, ESC and heartburn button until &#8220;complete&#8221; appears on the display.</li>
	</ol>
	</li>
	<li>Remove tape and gently pull out both catheters.</li>
</ol>
10. Interpreting the results obtained by the esophageal pH study
<ol>
	<li>Connect the device to a computer. Open the software used for analyzing results obtained from the esophageal pH measuring device and upload the patient&#8217;s study.</li>
	<li>Manually type in the patient&#8217;s data and the information obtained by the patient&#8217;s diary, such as mealtimes, upright and supine periods and symptoms experienced during the study period. Delete any button presses that might have accidentally been performed by the patient during the study period.</li>
	<li>Exclude mealtimes from the data analysis.</li>
	<li>On the report, look at important parameters and thresholds provided to determine an abnormal esophageal acid exposure such as the composite score, the total % pH below baseline (upright and supine) and total number of events.</li>
	<li>Calculate a composite score (DeMeester score) for the study period using % time pH &#60; 4 total, upright and supine, total number of events, number of events lasting longer than 5 minutes and the duration of the longest event14. Make sure the report shows the composite score. 
	NOTE: A DeMeester score &#62; 14.72 displays an abnormal esophageal acid exposure.</li>
</ol>
11. Interpreting results obtained by laryngopharyngeal pH monitoring
<ol>
	<li>Insert the SD card into the computer and open the software used for analyzation of results obtained by the laryngopharyngeal pH measuring system. To upload the study, click on Retrieve.</li>
	<li>Manually add the information obtained by the patient&#8217;s diary, such as mealtimes, upright and supine periods and symptoms experienced during the study period. Left click on the graph and drag and highlight the area on which you want to add the event and choose the respective event. Delete any button presses that might have accidentally been performed by the patient during the study period.</li>
	<li>Exclude mealtimes from the data analysis.</li>
	<li>Click on Report to see a graph displaying acid exposure in the oropharynx during the study period, including supine period, symptoms and mealtimes as well as a study summary.</li>
	<li>On the report, look at important parameters and thresholds to determine an abnormal oropharyngeal acid exposure such as the composite score, the total % pH below baseline (pH &#60; 5.5 upright and pH &#60; 5 supine) and total number of events.</li>
	<li>Calculate a composite score (RYAN Score) for both the upright and supine period using the % time pH below 5.5 upright and 5 supine, total number of events and the duration of the longest event8. Make sure, a composite score for the upright and supine period is shown in the report. 
	NOTE: A RYAN Score of &#62; 9.4 upright and &#62; 6.8 supine shows a severely abnormal oropharyngeal acid exposure.</li>
</ol>

<ol>
	<li>Dent, J., El-Serag, H. B., Wallander, M. A., Johansson, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Epidemiology+of+gastro-oesophageal+reflux+disease:+a+systematic+review.">Epidemiology of gastro-oesophageal reflux disease: a systematic review.</a> Gut. 54 (5), 710-717 (2005).</li><li>Koop, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=S2k+guideline:+gastroesophageal+reflux+disease+guided+by+the+German+Society+of+Gastroenterology:+AWMF+register+no.+021-013.">S2k guideline: gastroesophageal reflux disease guided by the German Society of Gastroenterology: AWMF register no. 021-013.</a> Zeitschrift f&#252;r Gastroenterologie. 52 (11), 1299-1346 (2014).</li><li>Becker, V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=New+aspects+in+the+pathomechanism+and+diagnosis+of+the+laryngopharyngeal+reflux-clinical+impact+of+laryngeal+proton+pumps+and+pharyngeal+pH+metry+in+extraesophageal+gastroesophageal+reflux+disease.">New aspects in the pathomechanism and diagnosis of the laryngopharyngeal reflux-clinical impact of laryngeal proton pumps and pharyngeal pH metry in extraesophageal gastroesophageal reflux disease.</a> World Journal of Gastroenterology. 21 (3), 982-987 (2015).</li><li>Vakil, N., van Zanten, S. V., Kahrilas, P., Dent, J., Jones, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Montreal+definition+and+classification+of+gastroesophageal+reflux+disease:+a+global+evidence-based+consensus.">The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus.</a> American Journal of Gastroenterology. 101 (8), 1900-1920 (2006).</li><li>Issing, W. J., Karkos, P. D., Perreas, K., Folwaczny, C., Reichel, O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dual-probe+24-hour+ambulatory+pH+monitoring+for+diagnosis+of+laryngopharyngeal+reflux.">Dual-probe 24-hour ambulatory pH monitoring for diagnosis of laryngopharyngeal reflux.</a> Journal of Laryngology &amp; Otology. 118 (11), 845-848 (2004).</li><li>Smit, C. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ambulatory+pH+measurements+at+the+upper+esophageal+sphincter.">Ambulatory pH measurements at the upper esophageal sphincter.</a> Laryngoscope. 108 (2), 299-302 (1998).</li><li>Worrell, S. G., DeMeester, S. R., Greene, C. L., Oh, D. S., Hagen, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pharyngeal+pH+monitoring+better+predicts+a+successful+outcome+for+extraesophageal+reflux+symptoms+after+antireflux+surgery.">Pharyngeal pH monitoring better predicts a successful outcome for extraesophageal reflux symptoms after antireflux surgery.</a> Surgical Endoscopy. 27 (11), 4113-4118 (2013).</li><li>Ayazi, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+technique+for+measurement+of+pharyngeal+pH:+normal+values+and+discriminating+pH+threshold.">A new technique for measurement of pharyngeal pH: normal values and discriminating pH threshold.</a> Journal of Gastrointestinal Surgery. 13 (8), 1422-1429 (2009).</li><li>Becker, V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=First+agreement+analysis+and+day-to-day+comparison+of+pharyngeal+pH+monitoring+with+pH/impedance+monitoring+in+patients+with+suspected+laryngopharyngeal+reflux.">First agreement analysis and day-to-day comparison of pharyngeal pH monitoring with pH/impedance monitoring in patients with suspected laryngopharyngeal reflux.</a> Journal of Gastrointestinal Surgery. 16 (6), 1096-1101 (2012).</li><li>Wilhelm, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pharyngeal+pH+monitoring+in+gastrectomy+patients+-+what+do+we+really+measure.">Pharyngeal pH monitoring in gastrectomy patients - what do we really measure.</a> United European Gastroenterology Journal. 4 (4), 541-545 (2016).</li><li>Mazzoleni, G., Vailati, C., Lisma, D. G., Testoni, P. A., Passaretti, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Correlation+between+oropharyngeal+pH-monitoring+and+esophageal+pH-impedance+monitoring+in+patients+with+suspected+GERD-related+extra-esophageal+symptoms.">Correlation between oropharyngeal pH-monitoring and esophageal pH-impedance monitoring in patients with suspected GERD-related extra-esophageal symptoms.</a> Neurogastroenterology &amp; Motility. 26 (11), 1557-1564 (2014).</li><li>Fuchs, H. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Simultaneous+laryngopharyngeal+pH+monitoring+(Restech)+and+conventional+esophageal+pH+monitoring-correlation+using+a+large+patient+cohort+of+more+than+100+patients+with+suspected+gastroesophageal+reflux+disease.">Simultaneous laryngopharyngeal pH monitoring (Restech) and conventional esophageal pH monitoring-correlation using a large patient cohort of more than 100 patients with suspected gastroesophageal reflux disease.</a> Dis Esophagus. 31 (10), (2018).</li><li>Fuchs, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Refluxassoziierte+Ver&#228;nderungen+des+Rest&#246;sophagus+nach+&#214;sophagektomie+und+Magenhochzug+-+Funktionsdiagnostik+im+Langzeitverlauf+bei+Patienten+mit+&#214;sophaguskarzinom+mit+einem+neuen+Instrument.">Refluxassoziierte Ver&#228;nderungen des Rest&#246;sophagus nach &#214;sophagektomie und Magenhochzug - Funktionsdiagnostik im Langzeitverlauf bei Patienten mit &#214;sophaguskarzinom mit einem neuen Instrument.</a> Zeitschrift f&#252;r Gastroenterologie. 54 (08), 436 (2016).</li><li>Jamieson, J. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ambulatory+24-h+esophageal+pH+monitoring:+normal+values,+optimal+thresholds,+specificity,+sensitivity,+and+reproducibility.">Ambulatory 24-h esophageal pH monitoring: normal values, optimal thresholds, specificity, sensitivity, and reproducibility.</a> American Journal of Gastroenterology. 87 (9), 1102-1111 (1992).</li><li>M&#252;ller, D. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Software+improvement+for+evaluation+of+laryngopharyngeal+pH+testing+(Restech)+-+a+comparison+between+DataView+3+and+4.">Software improvement for evaluation of laryngopharyngeal pH testing (Restech) - a comparison between DataView 3 and 4.</a> World Journal of Gastrointestinal Surgery. 12 (5), 236-246 (2020).</li><li>Weitzendorfer, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pepsin+and+oropharyngeal+pH+monitoring+to+diagnose+patients+with+laryngopharyngeal+reflux.">Pepsin and oropharyngeal pH monitoring to diagnose patients with laryngopharyngeal reflux.</a> Laryngoscope. 130 (7), 1780-1786 (2020).</li><li>Neto, R. M. L., Herbella, F. A. M., Schlottmann, F., Patti, M. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Does+DeMeester+score+still+define+GERD.">Does DeMeester score still define GERD.</a> Dis Esophagus. 32 (5), (2019).</li><li>Anandasabapathy, S., Jaffin, B. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multichannel+intraluminal+impedance+in+the+evaluation+of+patients+with+persistent+globus+on+proton+pump+inhibitor+therapy.">Multichannel intraluminal impedance in the evaluation of patients with persistent globus on proton pump inhibitor therapy.</a> Annals of Otology, Rhinology &amp; Laryngology. 115 (8), 563-570 (2006).</li></ol>

Dolores M&#252;ller received an educational grant from Restech. All other authors have nothing to disclose.

Esophageal pH monitoring is commonly used to confirm the diagnosis of GERD in patients with typical reflux symptoms. However, many patients present, in addition to typical reflux symptoms, with atypical reflux symptoms such as cough or hoarseness most likely related to LPR. Current guidelines suggest an empiric trial with PPIs to proof a reflux related origin of those symptoms and a standardized objective measurement is lacking2. Laryngopharyngeal pH testing, due to its location above the upper es...

Gastroesophageal reflux disease (GERD) is one of the most common benign diseases affecting up to 20% of people in western countries1. In addition to typical symptoms such as heartburn or regurgitation, some patients may suffer from atypical symptoms such as cough, hoarseness, or asthma2,3. Despite the agreement that chronic cough, chronic laryngitis, and asthma can have a reflux related origin and are significantly associated with laryngopharyngeal reflux (LPR), the exact pathomechanism still remains unclear. As these symptoms are usually part of a multifactorial process, they depict a great diagnostic and therapeutic challenge4.
Distal esophageal pH monitoring 5 cm above the lower esophageal sphincter is commonly used to determine abnormal esophageal acid exposure in patients with suspected GERD2. In an attempt to use the same technique, proximal conventional pH monitoring was introduced in the late 1990s as a diagnostic device to measure abnormal acid exposure at the upper esophageal sphincter (UES) as the probe is placed at or slightly above the UES. However, this method does not always provide valid and accurate results as the probe is not designed for an oropharyngeal environment leading to the measurement of invalid artifacts such as pseudoreflux events caused by drying out of the probe5,6.
Lately, laryngopharyngeal pH monitoring was introduced as a new diagnostic device specifically designed to measure acid exposure in the oropharynx, as the probe is placed above the UES slightly lateral to the uvula (Figure 1). Since previous research has shown it to have a positive predictive value of 80% for a successful outcome after antireflux surgery in patients with primarily atypical symptoms, this new tool has been a valuable addition to the diagnostic pathway in selected patients. Its tear drop sensor is equipped with an antimony technology that detects liquid and aerosolized acid and does not need direct mucosal contact to measure valid results. In addition, the sensor can, in contrast to proximal pH monitoring, resist drying out which may lead to more reliable results7,8.
Current literature on the correlation of concomitant conventional esophageal and laryngopharyngeal pH measurement is sparse. Previous studies either included only a small number of patients or did not perform both measurements simultaneously9,10,11. We recently published data on the correlation between both pH measurements in a large cohort of 101 patients with suspected GERD. We concluded that laryngopharyngeal and esophageal pH measurement do not necessarily need to correspond due to the existence of a variety of different reflux scenarios12. We furthermore developed a human reflux model with patients following esophagectomy and reconstruction with a gastric interposition showing 100% correlation between both pH monitoring methods in volume-refluxers13.
Here, we aim to provide instructions for simultaneous pH measurement using distal esophageal and laryngopharyngeal pH monitoring. In addition, guidance on analysis of composite acid exposure scores and correlation between results obtained by both methods is given. We furthermore present the newest data of a large patient cohort evaluated using simultaneous esophageal and laryngopharyngeal pH monitoring.

<table>
	<tbody>
		<tr>
			<td>AA Battery</td>
			<td>-</td>
			<td>-</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Calibration Solutions pH 4 and 7</td>
			<td>Medtronic</td>
			<td></td>
			<td>part of the Digitrapper Reflux Testing system</td>
		</tr>
		<tr>
			<td>CR 1632 Lithium coin cell battery</td>
			<td>-</td>
			<td>-</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Digitrapper pH &#38; Impedance catheter</td>
			<td>Medtronic</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Digitrapper Recorder</td>
			<td>Medtronic</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Gelicain</td>
			<td>PUREN</td>
			<td></td>
			<td>topical gel</td>
		</tr>
		<tr>
			<td>Hydration vials with clear water</td>
			<td>Respiratory Technology Corporation</td>
			<td></td>
			<td>part of the Restech Dx pH system</td>
		</tr>
		<tr>
			<td>Leukoplast</td>
			<td>BSN medical GmbH</td>
			<td></td>
			<td>surgical tape</td>
		</tr>
		<tr>
			<td>Restech Dx pH probe</td>
			<td>Respiratory Technology Corporation</td>
			<td></td>
			<td>part of the Restech Dx pH system</td>
		</tr>
		<tr>
			<td>Restech Recorder</td>
			<td>Respiratory Technology Corporation</td>
			<td></td>
			<td>part of the Restech Dx pH system</td>
		</tr>
		<tr>
			<td>Restech Transmitter</td>
			<td>Respiratory Technology Corporation</td>
			<td></td>
			<td>part of the Restech Dx pH system</td>
		</tr>
		<tr>
			<td>Screwdriver</td>
			<td>Respiratory Technology Corporation</td>
			<td></td>
			<td>part of the Restech Dx pH system</td>
		</tr>
		<tr>
			<td>SD Card plus Adapter</td>
			<td>Respiratory Technology Corporation</td>
			<td></td>
			<td>part of the Restech Dx pH system</td>
		</tr>
		<tr>
			<td>tongue depressor</td>
			<td>NOBAMED</td>
			<td></td>
			<td>wooden</td>
		</tr>
	</tbody>
</table>

simultaneous laryngopharyngeal and conventional esophageal ph monitoring

In addition to typical reflux symptoms, many patients with gastroesophageal reflux disease (GERD) present with extraesophageal symptoms such as cough, hoarseness or asthma, which can be caused by laryngopharyngeal reflux (LPR). Due to their multifactorial origin, those symptoms can be a great diagnostic and therapeutic challenge. Esophageal pH-monitoring is commonly used to determine abnormal esophageal acid exposure and confirm the diagnosis of GERD. However, for better evaluation of acid exposure above the upper esophageal sphincter, a new laryngopharyngeal pH measurement system is now available and may lead to more reliable results in patients with predominantly extraesophageal symptoms. This article aims to present a standardized protocol for simultaneous pH measurement using esophageal and laryngopharyngeal pH probes in order to obtain acid exposure scores from both measurements.

A total of 181 patients were evaluated using the previously described standardized protocol. Results of the first 101 patients have been previously published12. The following data depicts an extension of the previously published cohort, however, evaluated using the new software for analyzation of results obtained by laryngopharyngeal pH testing15. Demographic data is depicted in Table 1. All patients presented with atypical symptoms including chronic cough,...

Watch this Scientific Journal Video about Simultaneous Laryngopharyngeal and Conventional Esophageal pH Monitoring at JoVE.com

Simultaneous Laryngopharyngeal and Conventional Esophageal pH Monitoring

Laryngopharyngeal pH monitoring has been specifically designed to measure acid exposure above the upper esophageal sphincter and complements diagnostic evaluation in patients that present with mainly extraesophageal reflux symptoms. Patients with suspected laryngopharyngeal reflux (LPR) were evaluated using distal esophageal and laryngopharyngeal pH testing simultaneously.

In addition to typical reflux symptoms, many patients with gastroesophageal reflux disease (GERD) present with extraesophageal symptoms such as cough, ...

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2.7K Views.  University of Cologne. Laryngopharyngeal pH monitoring has been specifically designed to measure acid exposure above the upper esophageal sphincter and complements diagnostic evaluation in patients that present with mainly extraesophageal reflux symptoms. Patients with suspected laryngopharyngeal reflux (LPR) were evaluated using distal esophageal and laryngopharyngeal pH testing simultaneously.

Video: Simultaneous Laryngopharyngeal and Conventional Esophageal pH Monitoring

Monitoring of Systemic and Hepatic Hemodynamic Parameters in Mice

The use of mouse models in experimental research is of enormous importance for the study of hepatic physiology and pathophysiological disturbances. However, due to the small size of the mouse, technical details of the intraoperative monitoring procedure suitable for the mouse were rarely described. Previously we have reported a monitoring procedure to obtain hemodynamic parameters for rats. Now, we adapted the procedure to acquire systemic and hepatic hemodynamic parameters in mice, a species ten-fold smaller than rats. This film demonstrates the instrumentation of the animals as well as the data acquisition process needed to assess systemic and hepatic hemodynamics in mice. Vital parameters, including body temperature, respiratory&#160;rate&#160;and heart&#160;rate were recorded throughout the whole procedure. Systemic hemodynamic parameters consist of carotid artery pressure (CAP) and central venous pressure (CVP). Hepatic perfusion parameters include portal vein pressure (PVP), portal flow rate as well as the flow rate of the common hepatic artery (table 1). Instrumentation and data acquisition to record the normal values was completed within 1.5 h. Systemic and hepatic hemodynamic parameters remained within normal ranges during this procedure.
This procedure is challenging but feasible. We have already applied this procedure to assess hepatic hemodynamics in normal mice as well as during 70% partial hepatectomy and in liver lobe clamping experiments. Mean PVP after resection (n= 20), was 11.41&#177;2.94 cmH2O which was significantly higher (P&#60;0.05) than before resection (6.87&#177;2.39 cmH2O). The results of liver lobe clamping experiment indicated that this monitoring procedure is sensitive and suitable for detecting small changes in portal pressure and portal flow rate. In conclusion, this procedure is reliable in the hands of an experienced micro-surgeon but should be limited to experiments where mice are absolutely needed.

This film demonstrates how to acquire systemic and hepatic hemodynamics in mice. The whole monitoring includes acquisition of vital parameters, systemic blood pressure, central venous pressure, common hepatic artery flow rate, and portal vein pressure as well as the portal flow rate in mice.

The use of mouse models in experimental research is of enormous importance for the study of hepatic physiology and pathophysiological disturbances. ...

A Rat Model of Ventricular Fibrillation and Resuscitation by Conventional Closed-chest Technique

A rat model of electrically-induced ventricular fibrillation followed by cardiac resuscitation using a closed chest technique that incorporates the basic components of cardiopulmonary resuscitation in humans is herein described. The model was developed in 1988 and has been used in approximately 70 peer-reviewed publications examining a myriad of resuscitation aspects including its physiology and pathophysiology, determinants of resuscitability, pharmacologic interventions, and even the effects of cell therapies. The model featured in this presentation includes: (1) vascular catheterization to measure aortic and right atrial pressures, to measure cardiac output by thermodilution, and to electrically induce ventricular fibrillation; and (2) tracheal intubation for positive pressure ventilation with oxygen enriched gas and assessment of the end-tidal CO2. A typical sequence of intervention entails: (1) electrical induction of ventricular fibrillation, (2) chest compression using a mechanical piston device concomitantly with positive pressure ventilation delivering oxygen-enriched gas, (3) electrical shocks to terminate ventricular fibrillation and reestablish cardiac activity, (4) assessment of post-resuscitation hemodynamic and metabolic function, and (5) assessment of survival and recovery of organ function. A robust inventory of measurements is available that includes &#8211; but is not limited to &#8211; hemodynamic, metabolic, and tissue measurements. The model has been highly effective in developing new resuscitation concepts and examining novel therapeutic interventions before their testing in larger and translationally more relevant animal models of cardiac arrest and resuscitation.

This article describes a rat model of electrically-induced ventricular fibrillation and resuscitation by chest compression, ventilation, and delivery of electrical shocks that simulates an episode of sudden cardiac arrest and conventional cardiopulmonary resuscitation. The model enables gathering insights on the pathophysiology of cardiac arrest and exploration of new resuscitation strategies.

A rat model of electrically-induced ventricular fibrillation followed by cardiac resuscitation using a closed chest technique that incorporates the basic ...

Simultaneous PET/MRI Imaging During Mouse Cerebral Hypoxia-ischemia

Dynamic changes in tissue water diffusion and glucose metabolism occur during and after hypoxia in cerebral hypoxia-ischemia reflecting a bioenergetics disturbance in affected cells. Diffusion weighted magnetic resonance imaging (MRI) identifies regions that are damaged, potentially irreversibly, by hypoxia-ischemia. Alterations in glucose utilization in the affected tissue may be detectable by positron emission tomography (PET) imaging of 2-deoxy-2-(18F)fluoro-&#7429;-glucose ([18F]FDG) uptake. Due to the rapid and variable nature of injury in this animal model, acquisition of both modes of data must be performed simultaneously in order to meaningfully correlate PET and MRI data. In addition, inter-animal variability in the hypoxic-ischemic injury due to vascular differences limits the ability to analyze multi-modal data and observe changes to a group-wise approach if data is not acquired simultaneously in individual subjects. The method presented here allows one to acquire both diffusion-weighted MRI and [18F]FDG uptake data in the same animal before, during, and after the hypoxic challenge in order to interrogate immediate physiological changes.

The method presented here uses simultaneous positron emission tomography and magnetic resonance imaging. In the cerebral hypoxia-ischemia model, dynamic changes in diffusion and glucose metabolism occur during and after injury. The evolving and irreproducible damage in this model necessitates simultaneous acquisition if meaningful multi-modal imaging data are to be acquired.

Dynamic changes in tissue water diffusion and glucose metabolism occur during and after hypoxia in cerebral hypoxia-ischemia reflecting a bioenergetics ...

Surgical Models of Gastroesophageal Reflux with Mice

Multiple surgical procedures have been reported to induce gastroesophageal reflux in animals. Herein, we report three surgical models with mice aiming to induce reflux of gastric contents, duodenal contents or mixed contents. Surgical procedures and general principles have been described in detail. A researcher with surgical experience should be able to grasp the technique after a short period of practice. After surgery, most mice can survive and develop reflux esophagitis similar to that in humans. However, it should be noted that histological differences between mouse and human esophagus are the inherent limitations of these surgical models. If used for research on Barrett&#8217;s esophagus and adenocarcinoma, these procedures may need to be combined with genetic modifications.

This article demonstrates surgical procedures of gastroesophageal reflux with mice. These models are useful tools for research on mechanisms and treatment of gastroesophageal reflux disease and potentially Barrett&#8217;s esophagus and esophageal adenocarcinoma.

Multiple surgical procedures have been reported to induce gastroesophageal reflux in animals. Herein, we report three surgical models with mice aiming to ...

Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis

Keratoconus is a bilateral and progressive corneal ectasia. In order to slow down its progression, corneal collagen cross-linking (CXL) has recently been introduced as an efficient treatment option. In biological and chemical sciences, crosslinking refers to new chemical bonds formed between reactive molecules. Hence, the aim of corneal collagen CXL is to synthetically increase the formation of crosslinks between collagen fibrils in the corneal stroma. Despite the fact that the efficiency of the conventional CXL (C-CXL) protocol has already been shown in several clinical studies, it might benefit from improvements in duration of the procedure and removal of corneal epithelium. Hence, in order to provide a coherent evaluation of two new and optimized CXL protocols, we studied keratoconus patients who had undergone one of the three CXL treatments: iontophoresis (I-CXL), accelerated CXL (A-CXL), and conventional CXL (C-CXL). A-CXL is a 6 time faster CXL procedure using a ten time higher UVA irradiance but still including an epithelium removal. Iontophoresis is a transepithelial non-invasive technique in which a small electric current is applied to improve riboflavin penetration throughout the cornea. Using anterior segment optical coherence tomography (AS OCT) and in vivo confocal microscopy (IVCM), we conclude that regarding the depth of treatment penetration, conventional CXL protocol remains the standard for treating progressive keratoconus. Accelerated CXL seems to be a quick, effective and safe alternative to treat thin corneas. The use of iontophoresis is still being investigated and should be considered with greater caution.

Corneal collagen cross-linking (CXL) is the only conservative treatment currently available to halt keratoconus progression by improving the biomechanical rigidity of the corneal stroma. The aim of this manuscript is to highlight the methods of three different protocols of CXL: conventional CXL (C-CXL), accelerated CXL (A-CXL), and iontophoresis CXL (I-CXL).

Keratoconus is a bilateral and progressive corneal ectasia. In order to slow down its progression, corneal collagen cross-linking (CXL) has recently been ...

ADSC-sheet Transplantation to Prevent Stricture after Extended Esophageal Endoscopic Submucosal Dissection

In past years, the cell-sheet construct has spurred wide interest in regenerative medicine, especially for reconstructive surgery procedures. The development of diversified technologies combining adipose tissue-derived stromal cells (ADSCs) with various biomaterials has led to the construction of numerous types of tissue-engineered substitutes, such as bone, cartilage, and adipose tissues from rodent, porcine, or human ADSCs. Extended esophageal endoscopic submucosal dissection (ESD) is responsible for esophageal stricture formation. Stricture prevention remains challenging, with no efficient treatments available. Previous studies reported the effectiveness of mucosal cell-sheet transplantation in a canine model and in humans. ADSCs are attributed anti-inflammatory properties, local immune modulating effects, neovascularization induction, and differentiation abilities into mesenchymal and non-mesenchymal lineages. This original study describes the endoscopic transplantation of an ADSC tissue-engineered construct to prevent esophageal stricture in a swine model. The ADSC construct was composed of two allogenic ADSC sheets layered upon each other on a paper support membrane. The ADSCs were labeled with the PKH67 fluorophore to allow probe-based confocal laser endomicroscopy (pCLE) monitoring. On the day of transplantation, a 5-cm and hemi-circumferential ESD known to induce esophageal stricture was performed. Animals were immediately endoscopically transplanted with 4 ADSC constructs. The complete adhesion of the ADSC constructs was obtained after 10 min of gentle application. Animals were sacrificed on day 28. All animals were successfully transplanted. Transplantation was confirmed on day 3 with a positive pCLE evaluation. Compared to transplanted animals, control animals developed severe strictures, with major fibrotic tissue development, more frequent alimentary trouble, and reduced weight gain. In our model, the transplantation of allogenic ADSCs, organized in double cell sheets, after extended ESD was successful and strongly associated with a lower esophageal stricture rate.

This study reports a successful method of endoscopical adipose tissue-derived stromal cell (ADSC)-sheet transplantation for esophageal stricture prevention after an extended endoscopic submucosal dissection (ESD) in a swine model.

In past years, the cell-sheet construct has spurred wide interest in regenerative medicine, especially for reconstructive surgery procedures. The ...

Esophageal Heat Transfer for Patient Temperature Control and Targeted Temperature Management

Controlling patient temperature is important for a wide variety of clinical conditions. Cooling to normal or below normal body temperature is often performed for neuroprotection after ischemic insult (e.g. hemorrhagic stroke, subarachnoid hemorrhage, cardiac arrest, or other hypoxic injury). Cooling from febrile states treats fever and reduces the negative effects of hyperthermia on injured neurons. Patients are warmed in the operating room to prevent inadvertent perioperative hypothermia, which is known to cause increased blood loss, wound infections, and myocardial injury, while also prolonging recovery time. There are many reported approaches for temperature management, including improvised methods that repurpose standard supplies (e.g., ice, chilled saline, fans, blankets) but more sophisticated technologies designed for temperature management are typically more successful in delivering an optimized protocol. Over the last decade, advanced technologies have developed around two heat transfer methods: surface devices (water blankets, forced-air warmers) or intravascular devices (sterile catheters requiring vascular placement). Recently, a novel device became available that is placed in the esophagus, analogous to a standard orogastric tube, that provides efficient heat transfer through the patient&#39;s core. The device connects to existing heat exchange units to allow automatic patient temperature management via a servo mechanism, using patient temperature from standard temperature sensors (rectal, Foley, or other core temperature sensors) as the input variable. This approach eliminates vascular placement complications (deep venous thrombosis, central line associated bloodstream infection), reduces obstruction to patient access, and causes less shivering when compared to surface approaches. Published data have also shown a high degree of accuracy and maintenance of target temperature using the esophageal approach to temperature management. Therefore, the purpose of this method is to provide a low-risk alternative method for controlling patient temperature in critical care settings.

This study presents a novel method to provide efficient patient temperature control for cooling or warming patients. A single use, triple lumen device is placed into the esophagus, analogous to a standard orogastric tube, and connects to existing heat exchange units to perform automatic patient temperature management.

Controlling patient temperature is important for a wide variety of clinical conditions. Cooling to normal or below normal body temperature is often ...

Absorbent Microbiopsy Sampling and RNA Extraction for Minimally Invasive, Simultaneous Blood and Skin Analysis

Conventional skin biopsy limits the clinical research that involves cosmetically sensitive areas or pediatric applications due to its invasiveness. Here, we describe the protocol for using&#160;an absorbent microneedle-based device, absorbent microbiopsy, for minimally invasive sampling of skin and blood mixture. Our goal is to help facilitate rapid progress in clinical research, the establishment of biomarkers for skin disease and reducing the risk for clinical research participants. In contrast to conventional skin biopsy techniques, the absorbent microbiopsy can be performed within seconds and does not require intensive training due to its simple design. In this report, we describe the use of absorbent microbiopsy, including loading and application, on a&#160;volunteer. Then, we show how to isolate RNA from the absorbed sample. Finally, we demonstrate the use of quantitative reverse transcription PCR (RT-qPCR) to quantify mRNA expression levels of both blood (CD3E and CD19) and skin (KRT14 and TYR). The methods that we describe utilize off the shelf kits and reagents. This protocol offers a minimally invasive approach for simultaneous sampling of skin and blood within the same absorbent microbiopsy matrix. We have found human ethics committees, clinicians and volunteers to be supportive of this approach to dermatological research.

In this article, we demonstrate how the absorbent microbiopsy technique is performed and how the sample can be used for RNA extraction for simple and simultaneous sampling of skin and blood in a minimally invasive manner.

Conventional skin biopsy limits the clinical research that involves cosmetically sensitive areas or pediatric applications due to its invasiveness. Here, ...

Cardiac Magnetic Resonance for the Evaluation of Suspected Cardiac Thrombus: Conventional and Emerging Techniques

We present the conventional cardiac magnetic resonance (CMR) protocol for evaluating a suspected thrombus and highlight emerging techniques.&#160;The appearance of a mass on certain magnetic resonance (MR) sequences can help differentiate a thrombus from competing diagnoses such as a tumor. T1 and T2 signal characteristics of a thrombus are related to the evolution of hemoglobin properties. A thrombus typically does not enhance following contrast administration, which also helps differentiation from a tumor. We also highlight the emerging role of T1 mapping in the evaluation of a thrombus, which can add another level of support in diagnosis. Prior to any CMR exam, patient screening and interviews are critical to ensure safety and to optimize patient comfort. Effective communication during the exam between the technologist and the patient promotes proper breath holding technique and higher quality images. Volumetric post processing and structured reporting are helpful to ensure that the radiologist answers the ordering services&#39; question and communicates these results effectively. Optimal pre-MR safety evaluation, CMR exam execution, and post exam processing and reporting allow for delivery of high quality radiological service in the evaluation of a suspected cardiac thrombus.

The goal of this article is to describe how cardiac magnetic resonance can be used for the evaluation and diagnosis of a suspected cardiac thrombus. The method presented will describe data acquisition as well as the pre-procedure and post-procedure protocol.

We present the conventional cardiac magnetic resonance (CMR) protocol for evaluating a suspected thrombus and highlight emerging techniques.&#160;The ...

Simultaneous Electrocardiography Recording and Invasive Blood Pressure Measurement in Rats

For studies related to cardiovascular physiology or pathophysiology, blood pressure (BP) and electrocardiography are basic observational parameters. Research focusing on cardiovascular disease models, potential cardiovascular therapeutic targets or pharmaceutical agents requires assessment of systemic arterial pressure and heart rhythm changes. In situations where radio telemetry systems are not available or affordable, the technique of femoral artery cannulation is an alternative way to obtain intra-arterial pressure waveform recordings and systemic BP measurements. This technique is economical and can be performed with standard equipment in animal facilities. However, invasive arterial pressure recording requires cannulation of small arteries, which can be a challenging surgical skill. Here, we present step-by-step protocols for femoral artery cannulation procedures. Key procedures include the calibration of the data acquisition system, tissue dissection and femoral artery cannulation, and setup of the arterial cannulation system for pressure recording. Surface electrocardiography recording procedures are also included. We also present examples of BP recordings from normotensive and hypertensive rats. This protocol allows reliable direct recordings of systemic BP with simultaneous electrocardiography.

Here, we describe a setup for simultaneous recording of electrocardiography and intra-arterial blood pressure (BP) in experimental rats, which can be done with standard equipment in animal facilities and can be applied to physiological or pharmacological studies to investigate pathogenic or therapeutic mechanisms in cardiovascular medicine.

For studies related to cardiovascular physiology or pathophysiology, blood pressure (BP) and electrocardiography are basic observational parameters. ...