Positive Symptom Association Probability Research Articles

788 VARIABLE GEOGRAPHICAL DIFFERENCES OF AMBULATORY ESOPHAGEAL REFLUX MONITORING IN MEXICO

Abstract Ambulatory esophageal reflux monitoring (AEpH) is useful in evaluating persistent or refractory esophageal symptoms despite adequate pharmacologic and/or surgical therapy. There is limited information whether there are geographical or regional differences in the diagnostic outcome of this test. Aim Characterize the diagnostic outcome of AEpH in a diverse population of Mexico. Analyze whether there is regional geographical diagnostic variability. Methods Data was collected from four major referral centers representing diverse geographical areas of Mexico: Mexico City-Central (two centers, years 2016-2020), Veracruz-South (years 2015-2020) and Monterrey-North (years 2013-2020). Consecutive patients undergoing AEpH with persistent GERD symptoms despite PPI therapy and negative upper endoscopy (no erosive disease >C or D LA classification) were entered into a data base and analyzed. Patients were classified as: NERD (acid exposure time (AET > 6.0%); hypersensitive esophagus (normal AET and positive symptom index (SI) or positive symptom association probability [SAP]); functional heartburn (NL AET, neg SI/SAP). Statistics: ANOVA, Chi-square and descriptive methods were used to compare variables among groups. Results 969 cases met inclusion criteria: 311 (32.1%) Central, 430 (44.3%) South, and 228 (23.5%) North. The results are summarized in the table. There were more women 618(63.8%) than men 351(36.2%); p < 0.001 with a mean age 47.7 ± 14.3. Patients were older in Central-Mexico 49.3 ± 13.6 years vs South 47.5 ± 15 and North 46.1 ± 13.6; p = 0.033. Functional heartburn was the most common diagnosis overall and more prevalent in Central-Mexico 171(55%) vs North 97(42.5%) and South 160(37.2%); p < 0.001. NERD was more predominant in the South 171(39.8%) vs North 72(31.6%) and Central-Mexico 98(31.5%); p = 0.029. Hypersensitive esophagus was more frequent in the North 59(25.9%) vs South 99(23%), and Central 42(13.5%); p < 0.001. Conclusion This is the first large data base study to evaluate the outcome of ambulatory esophageal reflux pH testing in Mexico. Our findings indicate a geographical variability of GERD phenotypes and suggest that further investigations are warranted to determine the causes of this distribution.

Gastroesophageal reflux disease in pediatric esophageal atresia: Assessment of clinical symptoms and pH-impedance data.

BACKGROUNDEsophageal atresia (EA) is the most common congenital anomaly of the gastrointestinal tract. Gastroesophageal reflux disease (GERD) is a frequent and lifelong problem in these patients. GERD can be asymptomatic and the incidence of esophageal gastric and intestinal metaplasia (Barrett’s esophagus) is increased in adults with EA compared with the general population. Timely and accurate diagnosis of GERD is important to reduce long-term problems and this may be achieved by pH-impedance testing.AIMTo assess symptoms and pH-impedance data in children after EA, in order to identify their specific features of GERD.METHODSThis study was conducted from November 2017 to February 2020 and involved 37 children who had undergone EA via open surgical repair (51.35% boys, 48.65% girls; age range: 1-14 years, median: 4.99 years). GERD diagnosis was made based on multichannel intraluminal impedance/pH study and two groups were established: EA without GERD, n = 17; EA with GERD, n = 20. A control group was established with 66 children with proven GERD (68.18% boys, 31.82% girls; median age: 7.21 years), composed of a nonerosive reflux disease (referred to as NERD) group (n = 41) and a reflux esophagitis group (n = 25). Upper gastrointestinal endoscopy with a mucosal esophageal biopsy was performed on all patients.RESULTSThe most frequently observed symptom in EA patients with GERD and without GERD was cough (70% and 76.5% respectively). The number of patients with positive symptom association probability in the EA groups was significantly larger in the EA without GERD group (P = 0.03). In the control reflux esophagitis group, prevalence of gastrointestinal symptoms was significantly higher than in the NERD group (P = 0.017). For both EA groups, there was strong correlation with index of proximal events (IPE) and total proximal events (EA with GERD: 0.96, P < 0.001; EA without GERD: 0.97, P < 0.001) but level of IPE was significantly lower than in GERD patients without any surgical treatment (P < 0.001). Data on distal mean nocturnal baseline impedance were significantly different between the EA with GERD group (P < 0.001) and the two control groups but not between EA without GERD and the two control groups.CONCLUSIONMean nocturnal baseline impedance may have diagnostic value for GERD in EA children after open surgical repair. IPE might be an additional parameter of pH-impedance monitoring.

Laryngeal signs and pH-multichannel intraluminal impedance in infants and children: The missing ring: LPR and MII-pH in children

Objectiveto investigate the reliability of laryngeal reflux finding score (RFS) and symptom index (RSI) in assessing gastroesophageal reflux (GER) in children and infants. Methodspatients with laryngeal or respiratory symptoms, who underwent laryngoscopy and esophageal pH-impedance (MII-pH) were recruited. RSI and RFS were correlated to MII-pH results. A RSI>13, RFS>7, acid exposure index>7%, total reflux episodes>100/24 h in infants or>70/24 h in children, or a positive symptom index or association probability, were considered pathological. Analysis considering age (</>12 months) was performed. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the laryngeal scores were calculated. Results197 children (median 53 months, 61 infants) were enrolled. MII-pH was pathological in 5/10 patients with RFS>7, and in 17/31 with RSI>13. RFS>7 had 3.9% sensitivity, 93% specificity, a PPV of 50 and a NPV of 34 in predicting GER disease. RFS was inversely associated to weakly acidic and proximal GER. RSI>13 had 13% sensitivity, 83% specificity, and a PPV and NPV similar to RFS. RSI was significantly associated with the number of acid reflux episodes, and, in infants, with bolus exposure index. ConclusionsRSI and RFS aren't accurate in predicting GER in infants and children. Acid reflux relates to laryngeal symptoms, but neither acid, nor proximal and weakly acidic GER relate to laryngeal alterations.

Higher Esophageal Symptom Burden in Obese Subjects Results From Increased Esophageal Acid Exposure and Not From Dysmotility

Esophageal motor disorders (EMD) and pathologic reflux are often identified in obese individuals, but it is not clear how obesity contributes to these symptoms. We examined the relationships among symptom burden, EMD, acid exposure time (AET), symptom association probability, and body mass index (BMI). We performed a retrospective study of 1089 consecutive patients who underwent high-resolution manometry, of which 426 patients also underwent reflux monitoring off acid suppression, over a 2-year period at a tertiary referral center. Symptom burden was assessed by questionnaires to determine dominant symptom intensity (DSI; product of symptom severity, and frequency, on 5-point Likert scales) and global symptom severity (GSS; global esophageal symptoms on 10-cm visual analog scales) at the time of esophageal testing; BMIs were recorded. We compared proportions of patients with EMD and abnormal reflux burden among BMI categories and correlated them with symptom burden. Four-hundred thirty-three patients (39.8%) met the criteria for EMD. Esophageal outflow obstruction was observed in higher proportions of patients with low BMIs (underweight, 25.9%; normal, 14.1%; overweight, 13.9%; and obese, 9.8%; P= .037), but EMDs were less frequent in obese patients (P= .047), despite higher symptom burden compared with non-obese patients (DSI, 10.5 ± 0.3 vs 9.7 ± 0.2; P= .03 and GSS, 6.5 ± 1 vs 5.9 ± 1; P= .01). Among the 426 patients who underwent reflux monitoring, the proportions with total AET (P= .02), and upright AET (P < .001) increased among BMI categories, supine AET trended strongly (P= .06), in combination with increasing DSI and GSS (P ≤ .001 for each comparison). BMI correlated with symptom burden, higher AET, and positive symptom association probability (P< .01 for each analysis). Increased symptom burden in obese individuals correlates with esophageal acid burden but not with motor disorders.

Correlation between cardiorespiratory events and gastro-esophageal reflux in preterm and term infants: Analysis of predisposing factors

BackgroundThe association between cardiorespiratory events (CRE) and gastro-esophageal reflux (GER) among neonates is still controversial. AimsTo test such an association in preterm and term infants. Study designProspective observational study. SubjectsForty-seven infants with suspected GER and recurrent CRE admitted at a neonatal intensive care unit, who underwent simultaneous and synchronized 24-hour recording of heart rate (HR), peripheral oxygen saturation (SpO2) and pH-impedance monitoring (MII-pH). HR/SpO2 data were filtered to avoid artefactual episodes of hypoxia and hypoperfusion. Outcome measuresThe main outcome measure was the symptom association probability (SAP), with a 2-minute time window. Infants with positive (>95%) and negative (≤95%) SAP index tests were compared by univariate and multivariate statistics. ResultsMedian gestational age at birth was 294/7 weeks, median age at study 36 days. We recorded 3341 GER events and 4936 CRE (4710 desaturations, 226 bradycardias); 609/4936 (12%) CRE were temporally associated with GER episodes: 338 preceded and 271 followed GER events. The SAP index was significant in 5/47 (11%) patients. The SAP index including only CRE following GER events was significant in 3/47 (6%). There was no significant difference in the number of acid, weakly acid, non-acid, pH-only events preceding or following CRE between infants with SAP-positive and SAP-negative tests. Infants with positive SAP-index tests compared to those with SAP-negative tests had lower weight gain in the three days preceding the test and tended to have lower birth weight. ConclusionsGER and CRE were associated in <11% of patients. The evaluation of ponderal growth might be helpful in predicting such an association.

High-resolution Manometry Findings During Solid Swallows Correlate With Delayed Reflux Clearance and Acid Exposure Time in Non-erosive Reflux Disease Patients.

Background/AimsThe role of esophageal motility in determining gastroesophageal reflux disease (GERD) severity has not been completely evaluated. A few studies have investigated high-resolution manometry (HRM) patterns during solid swallows. The present study evaluates the HRM patterns of non-erosive reflux disease (NERD) patients during both liquid and solid swallows and their correlation with the severity of GERD.MethodsIn 23 NERD patients and 15 healthy volunteers (HVs) HRM was performed during a standard solid meal in a seated position, followed by 24-hour impedance-pH monitoring.ResultsOf the 31 patients, 10 showed a pathological acid exposure time (AET; NERD patients), 13 a normal pH profile with positive symptom association probability (SAP; reflux hypersensitivity patients), and 8 normal AET and SAP (functional heartburn patients). Mean distal contractile integral and distal latency values, in all patient groups and HVs, were significantly higher during solid swallows. In the group of 10 NERD patients, the number of large breaks of the esophageal peristalsis was 16 out of 100 liquid swallows (16%) and 31 out of 171 solid swallows (18%). Fourteen out of 100 liquid swallows (14%) and 25 out of 171 solid swallows (15%) resulted ineffective. Mean reflux clearing time at multichannel intraluminal impedance-pH was 17.6 ± 3.7 seconds. NERD patients presented, during solid swallows, a significantly higher proportion of large peristaltic breaks and of ineffective swallows than reflux hypersensitivity and functional heartburn patients.ConclusionHRM during solid swallows reveals motor abnormalities, undetected during liquid swallows, which might be involved in delaying reflux and acid clearance in patients with GERD.

Diagnostic yield of ambulatory oesophageal studies on versus off proton pump inhibitors: a systematic review and meta-analysis.

Patients with persistent gastroesophageal reflux disease symptoms despite proton pump inhibitors are increasingly encountered. It remains controversial if proton pump inhibitors should be stopped before functional oesophageal tests. This meta-analysis compares the positive yield of oesophageal studies performed off versus on proton pump inhibitors. Pubmed, Embase and the Cochrane Library were searched for eligible studies. Outcomes assessed were the number of subjects with: elevated oesophageal acid exposure time when studied off versus on proton pump inhibitors; positive symptom index (≥50%) and/or positive symptom association probability (≥95%) for acid reflux; and/or non-acid reflux events off versus on proton pump inhibitors. The random effects model was applied. Fifteen studies (n = 5033 individuals; 33% on proton pump inhibitors; 32% men; mean age 52.1 years) were analysed. Pooled risk ratio for the comparison of high oesophageal acid exposure time off versus on proton pump inhibitors was 2.16 (95% confidence interval (CI) 1.42-3.28). The risk ratio of a positive symptom index (acid reflux) was 2.64 (95% CI 1.52-4.57) and the risk ratio of a positive symptom association probability (acid reflux) was 2.94 (95% CI 2.31-3.74). Conversely, the risk ratio of a positive symptom index (non-acid reflux) was 0.96 (95% CI 0.49-1.88) and risk ratio of a positive symptom association probability (non-acid reflux) was 0.54 (95% CI 0.30-0.99). Oesophageal studies after proton pump inhibitor cessation improve the positive yield for acid reflux-related events but reduce the detection of symptomatic non-acid reflux events.

Clinical Impact of Increasing the Threshold for Distal Esophageal Acid Exposure Time (AET)

Introduction: A wireless pH capsule study with a composite score is a reliable method to quantify acid exposure in the distal esophagus. The optimal cut-off value for pathological acid exposure time is not standardized and ranges from 4.4% - 5.8% in different studies. We evaluated the reflux burden and symptom association of patients when the threshold for acid exposure time (AET) is varied from 4% to 6%. Methods: All 96-hour wireless pH capsule studies in our urban, academic gastroenterology practice between January 2016 and December 2017 were analyzed using AET greater than 4%, 5%, and 6% as the threshold for abnormal acid reflux to evaluate the differential yield of pathologic acid exposure with these alternative thresholds. All antacids or acid suppression medications were held for at least 7 days prior to the examinations. Results: A total of 257 consecutive patients (94 male, mean age 52.6 years (19-84 years) were included for analysis. Using the 4%, 5%, and 6% threshold values for overall AET; 19.8% (51), 27.6% (71), and 33% (85) patients did not have evidence of abnormal acid reflux respectively, over a 96-hour period. The evaluation of the 34 patients who were “missed” by increasing the AET from 4% to 6% showed: Median symptom association probability (SAP) for heartburn and regurgitation was 98.6 (IQR 84.3) and 72.4 (IQR 97.3), respectively. The median symptom index (SI) for heartburn and regurgitation was 26.8 (IQR 37) and 12.3 (IQR 25.7) respectively and the mean DeMeester score was 19.5 (range: 12.9 - 27). At 5% threshold value (14 out of 34 missed patients), SAP was positive (>95%) in 8 and 4 patients for heartburn and regurgitation respectively. The SI was positive (>50%) in 1 patient for heartburn and none for regurgitation. At 4% threshold value for AET (20 out of 34 missed patients), SAP was positive in 12 and 5 patients for heartburn and regurgitation respectively. The SI was positive in 3 patients for heartburn and 3 patients regurgitation. Conclusion: Increasing the percent AET from 4% to 6% reduces the identification of pathologic acid reflux by 14%. Using 6% as the AET threshold primarily reduces the identification of positive SAP and SI for heartburn and regurgitation symptoms to acid reflux. Patients in this group may represent a subgroup of reflux patients that specific targeted therapies may improve therapeutic outcomes and warrants further study.

Cardiorespiratory events in infants with gastroesophageal reflux symptoms: Is there any association?

Cardiorespiratory (CR) events (apnea, bradycardia, oxygen desaturation) and gastroesophageal reflux (GER) symptoms often coexist in infants admitted to Neonatal Intensive Care Unit, leading to over-prescription of drugs and delayed discharge. We aimed to evaluate the relationships between CR and GER events. The temporal associations between CR and GER events were analyzed in symptomatic infants who underwent synchronized CR and pH-impedance monitoring. The symptom association probability (SAP) index was used to identify infants with a significant number of temporal associations. Gastroesophageal reflux characteristics and the chronological sequence of CR and GER events occurring within 30seconds of each other were evaluated according to SAP index. Of the 66 infants enrolled, aged 29 (18-45) days, 58 had CR events during monitoring. From these 58 patients, a total of 1331 CR events and 5239 GER (24% acidic) were detected. The SAP index was positive in seven (12%) infants. These infants had greater GER frequency, duration, and proximal extent (P<.05). The number of temporal associations was 10 times greater in the positive SAP group. Gastroesophageal reflux events preceded CR events in 83% of these associations. These GER events had a higher proximal extent (P=.004), but showed no differences in pH values. The simultaneous evaluation of CR and GER events could be useful to identify infants with severe GER and significant temporal associations between these events. Treatment of GER could be indicated in these infants, but as the GER events involved are mainly non-acidic, empirical treatment with antacids is, often, inappropriate.

Hypopharyngeal multichannel intraluminal impedance leads to the promising outcome of antireflux surgery in Japanese population with laryngopharyngeal reflux symptoms.

Clinical characteristics of laryngopharyngeal reflux (LPR) in Japanese population remain unclear, and its treatment outcome is suboptimal. The objectives of this study were to evaluate Japanese patients with LPR symptoms using hypopharyngeal multichannel intraluminal impedance (HMII) and to assess the outcome of antireflux surgery (ARS). Subjects included patients who had LPR symptoms for > 12 weeks or laryngoscopic findings suggestive of LPR and underwent laryngoscopy and esophageal testing including HMII. Abnormal proximal exposure (APE) was defined as LPR ≥ 1/day and/or full column reflux (FCR) (reflux 2cm distal to the upper esophageal sphincter) ≥ 5/day on HMII. Patients with APE were offered ARS and the outcome of ARS was objectively assessed using Reflux Symptom Index (RSI). From July 2015 to September 2016, 52 patients with LPR symptoms (28 men, 24 women, median BMI 22.3) underwent HMII, and 38 patients (73%) had APE. Of them, 29 (76%) patients were not obese (BMI < 25) and 19 (50%) patients had a negative DeMeester score. Approximately one-third of LPR and FCR events were non-acid in the distal esophagus. A positive symptom-association probability was seen only in 18 patients (35%). Mild esophagitis and hiatal hernia were found in 5 (10%) and 23 (48%) patients, respectively. All 12 patients (100%) who had undergone ARS were able to discontinue PPI and had a significant improvement in the RSI scores postoperatively (22.9 ± 10.0 vs. 6.8 ± 6.8, p <.001). APE was frequently observed in Japanese patients with LPR symptoms. Obesity and esophagitis were uncommon in this population. Since a large number of patients with APE had negative DeMeester score and proximal reflux events were often non-acid, a conventional pH monitoring is insufficient. HMII is crucial to evaluate patients with LPR symptoms as the documentation of APE is a key for successful outcome of ARS.

Reflux-cough syndrome: Assessment of temporal association between reflux episodes and cough bursts.

Gastro-esophageal reflux can be the cause of chronic cough. In the assessment of the temporal association between reflux and cough, previous studies have used a two-minute time window, based on studies in patients with heartburn. However, it remains unclear whether the optimal time window duration for the evaluation of reflux-induced cough is two minutes as well. Therefore, we aimed to determine whether a two-minute time window is optimal to diagnose reflux-induced cough. In this multicenter study, 137 patients with chronic cough were evaluated using 24-h pH-impedance-pressure monitoring. Repetitive symptom association analysis was employed using an array of time windows of various duration. For each time window, the symptom association probability (SAP) and symptom index (SI) were calculated. A total of 4377 cough burst episodes and 5074 reflux episodes were detected. The number of patients with a positive SAP increased with increasing window duration until a plateau was reached around a time window duration of 1.5min. Similarly, the SI increased steeply until a window duration of about 2min, after which a linear increase was seen. A two-minute time window seems appropriate for evaluation of the relationship between reflux and chronic cough using 24-h pH-impedance-pressure monitoring. A time window duration of 30s or 1min is too short to diagnose patients with reflux-induced cough accurately.

The binomial symptom index for the evaluation of temporal association between cardiorespiratory symptoms and gastroesophageal reflux in neonates

Abstract Introduction The evaluation of symptom association between gastroesophageal reflux and cardiorespiratory events in preterm infants remains unclear. This paper describes a conservative approach to decision-making of anti-reflux surgery through symptom association analysis. Methods Forty-three neonates with potentially reflux-related cardiorespiratory symptoms underwent synchronized esophageal impedance-pH and cardiorespiratory monitoring. Three indices were considered to evaluate symptom association, the symptom index (SI), the symptom sensitivity index (SSI) and the symptom association probability (SAP). A conservative strategy was adopted regarding the decision of anti-reflux surgery, and therefore, patients were scheduled for laparoscopic Nissen fundoplication if the three indices showed a positive assessment of symptom association. Retrospectively, these indices and the binomial symptom index (BSI) were contrasted against the decision of anti-reflux surgery using different windows of association. Results Thirteen patients showed positive symptom association but only two underwent anti-reflux surgery. The SI and the SSI showed an increasing trend with the width of the window of association. The SAP was affected randomly by slightly altering the windowing parameters. The BSI showed the best performance with the two-minute window (κ = 0.78). Conclusions The pathology under study is known to improve with maturity. However, the severity of cardiorespiratory symptoms may threaten the neonate's life and therefore, on some occasions, invasive treatments must be considered to protect life. The BSI provides a good prediction of a combination of positive SI, SSI and SAP, which may improve clinical decisions. However, further clinical studies are required to prove the BSI as an optimal predictor of clinical outcomes.

Impairment of chemical clearance and mucosal integrity distinguishes hypersensitive esophagus from functional heartburn

Hypersensitive esophagus (HE) is defined by endoscopy-negative heartburn with a normal acid exposure time but positive symptom association probability (SAP) and/or symptom index (SI) on impedance-pH monitoring, and proton pump inhibitor (PPI) responsiveness. Functional heartburn (FH) is distinguished by negative SAP/SI and PPI refractoriness. The clinical value of SAP and SI has been questioned. We aimed to investigate whether impairment of chemical clearance and of mucosal integrity, expressed by the postreflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI), characterize HE independently of SAP and SI. Impedance-pH tracings from PPI-responsive endoscopy-negative patients, 125 with nonerosive reflux disease and 108 with HE, distinguished by an abnormal and a normal acid exposure time, and from 70 patients with FH were retrospectively selected and blindly reviewed. The mean PSPW index and MNBI were significantly lower in nonerosive reflux disease (30%, 1378Ω) than in HE (51%; 2274Ω) and in both of them as compared with FH (76%; 3445Ω) (P=0.0001). Both the PSPW index (adjusted odds ratio 0.863, P=0.001) and the MNBI (adjusted odds ratio 0.998, P=0.001) were independent predictors of HE; with their combined assessment, the area under the curve on receiver operating characteristic analysis was 0.957. SAP and/or SI was positive in 67 of the 108 HE patients (62%), whereas the PSPW index and/or MNBI was abnormal in 99 of the 108 HE patients (92%; P<0.0001). HE is characterized by impairment of chemical clearance and mucosal integrity, which explains the increased reflux perception. When SAP and SI afford uncertain results, the PSPW index and MNBI should be analyzed.

Prevalence, characteristics, and treatment outcomes of reflux hypersensitivity detected on pH-impedance monitoring.

Positive symptom association probability (SAP) with physiologic esophageal acid exposure time (AET) on pH-impedance monitoring defines reflux hypersensitivity (RH), a correlate of acid sensitivity on pH monitoring. We evaluated prevalence, clinical characteristics, and symptomatic outcomes of RH in a prospective observational cohort with reflux symptoms undergoing pH-impedance monitoring. Reflux hypersensitivity was diagnosed when SAP was positive with pH- and/or impedance-detected reflux events with physiologic AET. Symptom burden was assessed using dominant symptom intensity (DSI, product of symptom severity and frequency on 5-point Likert scales) and global symptom severity (GSS, global esophageal symptoms on 100-mm visual analog scales) by questionnaire, both at baseline and on prospective follow-up. Clinical characteristics and predictors of symptomatic improvement were assessed with univariate and multivariate analyses. Seventy-seven patients (29%) met criteria for RH, of which 53 patients (53.7 ± 1.8 years, 66% F) were contacted after 3.3 ± 0.2 years for follow-up. Reflux hypersensitivity was detected on pH-impedance testing both on and off antisecretory therapy; pH alone missed 51% of RH. About 57% reported ≥50% GSS improvement. Sixteen patients undergoing antireflux surgery (ARS) reported better symptom improvement compared to 37 patients treated medically (GSS change: p = 0.005; DSI change: p = 0.04). Hiatus hernia (p = 0.03) and surgical management (p ≤ 0.04) predicted symptom improvement on univariate analysis, while acid sensitivity was a negative predictor for outcome on both univariate (p = 0.02) and multivariate analyses (p ≤ 0.04). Reflux hypersensitivity is a mechanism for persistent reflux symptoms in almost one-third of patients undergoing pH-impedance testing. While acid sensitivity predicts suboptimal symptom improvement, antireflux therapy may improve RH in select settings.

El índice de síntomas binomial para la evaluación de la asociación temporal entre síntomas cardiorrespiratorios y reflujo gastroesofágico en neonatos

IntroductionThe evaluation of symptom association between gastroesophageal reflux and cardiorespiratory events in preterm infants remains unclear. This paper describes a conservative approach to decision-making of anti-reflux surgery through symptom association analysis. MethodsForty-three neonates with potentially reflux-related cardiorespiratory symptoms underwent synchronized esophageal impedance-pH and cardiorespiratory monitoring. Three indices were considered to evaluate symptom association, the symptom index (SI), the symptom sensitivity index (SSI) and the symptom association probability (SAP). A conservative strategy was adopted regarding the decision of anti-reflux surgery, and therefore, patients were scheduled for laparoscopic Nissen fundoplication if the three indices showed a positive assessment of symptom association. Retrospectively, these indices and the binomial symptom index (BSI) were contrasted against the decision of anti-reflux surgery using different windows of association. ResultsThirteen patients showed positive symptom association but only two underwent anti-reflux surgery. The SI and the SSI showed an increasing trend with the width of the window of association. The SAP was affected randomly by slightly altering the windowing parameters. The BSI showed the best performance with the two-minute window (κ =0.78) ConclusionsThe pathology under study is known to improve with maturity. However, the severity of cardiorespiratory symptoms may threaten the neonate's life and therefore, in some occasions, invasive treatments must be considered to protect life. The BSI provides a good prediction of a combination of positive SI, SSI and SAP, which may improve clinical decisions. However, further clinical studies are required to prove the BSI as an optimal predictor of clinical outcomes.

24-hour pH-impedance monitoring on therapy to select patients with refractory reflux symptoms for antireflux surgery. A single center retrospective study.

Treatment of gastro-esophageal reflux refractory symptoms is challenging. This monocenter retrospective study assessed the value of preoperative pH-impedance monitoring 'on' therapy to predict functional outcome after laparoscopic fundoplication in patients with refractory reflux symptoms. Patients with a preoperative pH-impedance monitoring 'on' proton pump inhibitors (PPIs) twice daily were assessed at least 6 months after a laparoscopic fundoplication for refractory reflux symptoms. Failure of fundoplication was defined by a Visick score > 2. Postoperative symptoms were assessed by the reflux disease questionnaire (RDQ). The pH-impedance parameters analyzed were the number of reflux events (total, acid, non-acid), esophageal acid exposure time, esophageal bolus exposure time, and symptom-reflux association defined by symptom index (SI) >50% and symptom association probability (SAP) >95%. Thirty-three patients (18 female patients, median age 46 years) were assessed after a mean follow-up of 41.3 (range 7-102.2) months. Seven (21.2%) patients were considered as failures. Compared to patients with favorable outcome, these patients were more often 'on' PPI therapy (86% vs 23%, p < 0.05) and had higher RDQ scores in each domain: heartburn (p < 0.05), regurgitation (p < 0.05) and dyspepsia (p < 0.05). A positive SAP was the only pH-impedance parameter statistically associated with successful postoperative outcome (p = 0.004). On therapy, a preoperative positive symptom association probability is the only pH-impedance parameter associated with favorable outcome after laparoscopic fundoplication for refractory reflux symptoms. These results should be confirmed by prospective studies.

Changes in symptom reflux association using dynamic pH thresholds during ambulatory pH monitoring: an observational cross-sectional study.

Symptom reflux association (SRA) assesses symptoms associated with reflux events defined by pH <4.0, but limited symptoms associate with reflux events. We evaluated the impact of alternate pH thresholds on SRA in a large ambulatory pH database. Acid exposure time (AET), reflux events, and associated symptoms (within 2 minutes following a reflux event) were extracted from ambulatory pH studies performed off antireflux therapy (722 patients, 49.1 ± 0.5 years, 66.8% F) over a 7-year period. Symptom association probability (SAP) and symptom index (SI) were calculated at pH 3.5, 4.0, 4.5, and 5. Receiver operating characteristics (ROC) were generated using SRA at any pH as gold standard; areas under the curve (AUCs) were determined. Discordant cases were reanalyzed to determine changes in SRA and predictors of change using multivariate regression. At pH 4.0, 41% had a positive SAP, and 34% had a positive SI. While there was sustained gain in SI positivity from acidic to more weakly acidic pH thresholds, SAP positivity was highest at pH 4.5. On ROC analysis, performance characteristics were best at pH 4.0 (AUC 0.97) for SAP, and at pH 4.5 and 5.0 (AUC 0.92-0.94) for SI. On multivariate logistic regression adjusting for age, gender, and change in AET and reflux events, only number of associated symptoms predicted change in SRA (P < 0.0001). Changing pH thresholds for reflux events augments SRA by increasing reflux events associated with existing symptoms, while symptom recording remains the principal determinant of SRA.

The combination of pH monitoring in the most distal esophagus and symptom association analysis markedly improves the clinical value of esophageal pH tests

Objective: The poor sensitivity of esophageal pH monitoring substantially limits the clinical value of the test. The aim of this study was to compare the diagnostic accuracy of esophageal pH monitoring and symptom association analysis performed at the conventional level with that obtained in the most distal esophagus. Material and methods: Eighty-two patients with typical reflux symptoms and 49 asymptomatic subjects underwent dual 48-h pH monitoring with the electrodes positioned immediately above, and 6 cm above the squamo-columnar junction (SCJ). The degree of esophageal acid exposure and the temporal relationship between reflux events and symptoms were evaluated. Results: The sensitivity of pH recording and the diagnostic yield of Symptom Association Probability (SAP) were significantly higher for pH monitoring performed at the distal compared with the conventional level (82% versus 65%, p<0.001 and 74% versus 62%, p<0.001, respectively). The greatest improvement was observed in patients with non-erosive disease. In this group, the sensitivity increased from 46% at the standard level to 66% immediately above the SCJ, and with the combination of a positive SAP as a marker for a positive pH test, the diagnostic yield further increased to 94%. Conclusion: The diagnostic accuracy of esophageal pH monitoring in the most distal esophagus is superior to that performed at the conventional level and it is further improved with the combination of symptom association analysis. PH monitoring with the pH electrode positioned immediately above the SCJ should be introduced in clinical practice and always combined with symptom association analysis.

Patients with refractory reflux symptoms often do not have GERD.

In patients with typical reflux symptoms that persist despite proton pump inhibitors (PPIs) it is sometimes overlooked that treatment fails due to the presence of other disorders than gastroesophageal reflux disease (GERD). The aim of this study was to determine the underlying cause of reflux symptoms not responding to PPI therapy in tertiary referral patients. Patients with reflux symptoms refractory to PPI therapy who underwent 24-h pH-impedance monitoring were analyzed. Patients in whom a diagnosis was already established before referral, who had previous esophageal or gastric surgery, or who had abnormalities on gastroscopy other than hiatus hernia, were excluded. In total, 106 patients were included. Esophageal manometry showed achalasia in two patients and distal esophageal spasm in another two. Twenty-four-hour pH-impedance monitoring revealed a total acid exposure time <6% in 60 patients (56.6%) of which 25 had a positive symptom association probability (SAP) while 35 showed a negative SAP. Sixty-nine patients ended up with a final diagnosis of GERD while 32 patients (30.2%) were diagnosed with functional heartburn (FH), two with functional chest pain, two with achalasia, and one with rumination. A trend toward an association with a final diagnosis of FH was found with the atypical symptom epigastric pain (p=0.059) and with a secondary diagnosis of functional dyspepsia (p=0.083). Approximately one-third of the patients referred with refractory reflux symptoms suffer from disorders other than GERD, predominantly FH. This explains, at least partly, why many patients will not benefit from acid inhibitory treatment.

PTH-179 Prolonged reflux monitoring may change the diagnosis of oesophageal hypersensitivity to pathological gastroesophageal reflux

<h3>Introduction</h3> Esophageal hypersensitivity is diagnosed in 5–12% of patients referred for reflux monitoring. These patients do not have pathological gastroesophageal reflux (GOR) which is mainly monitored for 24–48 h but perceive their symptoms with normal degree of GOR. As a result of such diagnosis clinicians tend to shift the focus of treatment from antireflux therapy to pain modulation agents. Our aim was to investigate change of diagnosis from oesophageal hypersensitivity to true GOR when more prolonged reflux monitoring is applied. <h3>Method</h3> All patients with heartburn and/or chest pain referred for prolonged wireless reflux monitoring in the period of January 2010 to February 2015 were selected for this retrospective study. Those with a positive reflux-symptom association for the above symptoms during the first 48 h of recording were included. The cut off for positive symptom association probability (SAP) was ≥95% and a positive symptom index (SI) was ≥50%. The total duration of reflux monitoring was 96 h. Presence of pathological GOR on the 3^rdand/or 4^th24 h of recording was considered as positive GORD. Change of diagnosis from oesophageal hypersensitivity to true reflux was identified. <h3>Results</h3> 183 patients with normal wireless pH monitoring at 48 hr completed a full 4 days study. During the 1st 48 h, 40 patients had positive SAP and/or SI for <b>heartburn</b>[13 males (M) and 27 females (F)]. Of these, 12 (30%) showed pathological GOR on extended monitoring (M: F- 3:9). The prevalence of pathological GOR on extended monitoring was: 11/38 (28.9%) patients with SAP + (regardless of SI), 4/13 (30.7%) with SI + (regardless of SAP), 8/27 (29.6%) with SAP + and SI –, 3/11 (27.3%) of those with both SAP and SI +. Only 2 patients were SAP –, SI + and only one had reflux. During the first 48 h, a total of 27 patients (M: F = 8: 19) with <b>chest pain</b>, had positive SAP and/or SI. Of these, 5 (18.5%) showed pathological reflux (M: F 1:4) during extended reflux monitoring. The prevalence of pathological GOR on extended monitoring was: 5/24 (20.8%) SAP + patients (regardless of SI), 4/10 (40%) with SI+ (regardless of SAP), 1/17 (5.9%) with SAP + and SI –, 4/7 (57.1%) with both SAP and SI +. <h3>Conclusion</h3> This study demonstrates that for the patients diagnosed with oesophageal hypersensitivity based on their chest pain or heartburn, this diagnosis can change in nearly 20 to 30% of the cases (respectively) to pathological GOR if prolonged reflux monitoring is applied. Diagnosis of oesophageal hypersensitivity might be partially technology or methodology dependent and modification of reflux monitoring methods can influence detection of GORD and oesophageal hypersensitivity. <h3>Disclosure of interest</h3> None Declared.