Clarithromycin-based Helicobacter pylori eradication therapy is not associated with higher treatment failure compared with non-clarithromycin-based regimens in a tertiary referral hospital in Switzerland.

BACKGROUND AND AIMS: Due to increasing antibiotic resistance, various Helicobacter pylori eradication regimens other than clarithromycin-based therapies have been proposed. However, detailed data on which therapies were employed and their eradication success is lacking. The purpose of this study was to analyse the response rates of different eradication therapy schemes. METHODS: In this retrospective cohort study, we analysed data of 1721 patients and included 608 patients undergoing H. pylori eradication therapy at the Department of Gastroenterology at the University Hospital Zurich between 2004 and 2018. The primary endpoint was the success rates of clarithromycin- and non-clarithromycin-containing H. pylori eradication regimens. We furthermore analysed factors with potential impact on the outcome of H. pylori eradication therapies, such as demographics, and smoking and social status. RESULTS: The most common therapy scheme (71% of all cases) was proton pump inhibitor (PPI)-amoxicillin-metronidazole, followed by PPI-amoxicillin-clarithromycin (21%) and PPI-metronidazole-clarithromycin (6%). There was no difference between the H. pylori eradication success of clarithromycin vs non-clarithromycin-containing therapies (71% vs 71%, p = 0.764). CONCLUSION: Despite increasing clarithromycin resistance globally, there was no difference in the eradication success of clarithromycin- and non-clarithromycin-containing therapy regimens in Switzerland. As varying triple therapies do not increase eradication rates in real-world settings, other primary therapy options such as quadruple therapies should be explored.

Diagnostic Delay in Patients With Eosinophilic Esophagitis Has Not Changed Since the First Description 30 Years Ago: Diagnostic Delay in Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic progressive disease. Diagnostic delay (DD) is associated with increased risk of esophageal strictures and food impactions. We aimed to assess the evolution of DD since the first description of EoE in 1993 until 2021. METHODS: We analyzed data from patients prospectively included in the Swiss EoE database. DD was calculated as the time interval between the first occurrence of EoE symptoms and the confirmed diagnosis. DD was analyzed annually over time (1989-2021) and according to milestone publications in the field (1993: first description; 2007: first consensus recommendations; and 2011: updated consensus recommendations). In addition, a Cox proportional hazards model has been used to describe the relation between DD and covariates. RESULTS: Complete data of 1,152 patients (857 male [74%]; median age at diagnosis: 38 years, interquartile range: 28-49, range: 1-86) were analyzed. Overall, median DD was 4 years (interquartile range: 1-11, range, 0-56), with DD ≥ 10 years in 32% of the population. Over time, DD did not significantly change, neither annually nor according to release dates of milestone publications with a persistently stable fraction of roughly one-third of all patients with a DD of ≥10 years. Both ages at diagnosis ( P < 0.001, with an increase in DD up to the age of 31-40 years) and at symptom onset (younger patients had a longer DD; P < 0.001) were significantly associated with DD. DISCUSSION: DD has not changed since the first description of EoE almost 30 years ago and remains substantial. Even today, one-third of patients have a persistently high DD of ≥10 years. Substantial efforts are warranted to increase awareness for EoE and its hallmark symptom, solid food dysphagia, as an age-independent red-flag symptom among healthcare professionals and presumably the general population alike to lower risk of long-term complications.

Subjective Sound Quality Detection (HISQUI) over Time after Vibrant Soundbridge Implantation.

BACKGROUND: To evaluate the long-term audiological outcomes combined with the Hearing Implant Sound Quality Index (HISQUI) after Vibrant Soundbridge (VSB) implantation. METHODS: Prospective recall cohort study of patients who received a VSB in a tertiary academic medical center between 1996 and 2017. Air conduction (AC) and bone conduction (BC), sound field thresholds in aided and unaided conditions, and speech discrimination in noise (Oldenburger sentence test) were measured. Postoperative results were compared with preoperative audiograms. Furthermore, the HISQUI was evaluated. RESULTS: Ten patients (eleven implants) were included, the mean follow up period was nine years. The mean AC threshold preoperatively was between 63 and 70 dB, and the BC was between 38 and 49 dB from 500 to 4000 Hz. In the free-field audiogram, the mean threshold was between 61 and 77 dB unaided vs. between 28 and 52 dB in the aided condition. The average signal to noise ratio (SNR) in the Oldenburger sentence test in the unaided condition was 10 dB ± 6.7 dB vs. 2 dB ± 5.4 dB in the aided condition. Three patients reported a good to very good hearing result, four patients a moderate, and three patients a poor hearing result. There was a significant association between the years of implantation and the HISQUI (p = 0.013), as well as a significant decrease by 14 HISQUI points per 10 dB SPL decline (SE 5.2, p = 0.023). There was a significant difference between the change of BC over the years and the HISQUI, as well as the number of years after implantation and the HISQUI. On average, per dB decrease in BC, the HISQUI decreases by 1.4 points, and every year after implantation the HISQUI decreases by 2.7 points. CONCLUSIONS: The aided threshold in free field and speech understanding in noise improved significantly with VSB. An increase over time of BC thresholds was observed as well as a decrease in HISQUI score. This decrease in BC thresholds over time may be due to presbycusis. Therefore, monitoring of these patients over time should be considered to discuss alternative hearing rehabilitation measures in a timely manner.

Permanent Tunneled Drainage of Ascites in Palliative Patients: Timing Needs Evaluation.

Background: Treatment of refractory ascites remains challenging. We evaluated the safety and efficacy of permanent tunneled peritoneal catheters (PTPC) in this condition. Methods: We retrospectively analyzed consecutive patients in palliative situations in a tertiary referral center. Safety parameters, symptom relief, and survival were assessed. Results: Seventy patients were included from February 2012 to January 2021. Ninety percent had ascites due to malignancy, 10% due to end-stage liver disease. The technical procedure was successful in all cases; no deaths occurred. Procedure-related infections were rare and only observed in patients without peri-interventional antibiotics. Most patients experienced symptom relief (76%) and were satisfied with the device (83%). Survival after PTPC was relatively short (median 19 days). Discussion: PTPC is a safe option for refractory ascites in palliative settings with symptom relief in the majority of patients and should be considered early after onset of ascites. Periprocedural antibiotic prophylaxis may be considered to avoid procedure-related infections.

Solid Swallow Examination During High Resolution Manometry and EGJ-Distensibility Help Identify Esophageal Outflow Obstruction in Non-obstructive Dysphagia.

Single water swallow (SWS) high-resolution manometry (HRM) may miss relevant esophageal motility disorders. Solid test meal (STM) during HRM and lately the functional lumen imaging probe (FLIP) have been shown to be of diagnostic value in the assessment of motility disorders. We aimed to assess the diagnostic yield of STM and FLIP in non-obstructive dysphagia (NOD). Patients assessed for dysphagia with both HRM and FLIP between April 2016 and August 2019 were analyzed for signs of non-obstructive EGJ outflow obstruction (EGJOO) according to Chicago Classification 3.0 (CCv3) and CC adapted for the use with solid swallows (CC-S), followed by an individual group-specific analysis. Five subjects without dysphagia served as control group. Standard HRM- and FLIP-values as well as esophagograms and Eckardt Scores were analyzed. Forty-two patients were identified (male/female, 14/36, median age 62). Twenty-five (59.5%) were diagnosed with EGJOO during STM only (= SWS-negative patients; CC-S). The EGJ distensibility index (EGJ-DI) of symptomatic patients was significantly lower compared to the control group (p = 0.006). EGJ-DI was < 3mm2/mmHg in 67% and 88% of patients diagnosed according to CC-S and CCv3, respectively. The IRP during STM showed a significant association to the corresponding EGJ-DI values (p < 0.001). Seventy-six percent of patients received treatment because of additional STM evaluation with a favorable clinical response rate of 89%. STM and FLIP identify EGJOO in symptomatic patients with normal SWS during HRM. STM resembles an inexpensive and clinically meaningful option to diagnose motility disorders and helps to select patients for interventional treatment.

Adding a liquid test meal to a standardized lactulose hydrogen breath test significantly influences abdominal symptom generation and hydrogen values.

OBJECTIVE: While single sugar tests are controversially discussed, combination tests with meals are gaining more attention. The aim of this study was to analyze the impact of adding a test meal to lactulose hydrogen breath tests (LHBT) on hydrogen values and abdominal symptoms in patients with functional gastrointestinal disorders (FGIDs). METHODS: Data of 81 FGID patients between 2014-2018 were analyzed. Patients underwent LHBT with 30 g lactulose + 300 mL water and a nutrient challenge test (NCT) including 400 mL liquid test meal + 30 g lactulose. To statistically assess the effect of a test meal on abdominal symptoms and H2, mixed-effect models were used. RESULTS: Adding a test meal to LHBT showed a significant increase in nausea [odds ratio (OR) 1.4; 95% confidence interval (CI), 1.1-1.7], decrease in abdominal pain (OR 0.7; 95% CI, 0.6-0.9), borborygmi (OR 0.5; 95% CI, 0.4-0.6), diarrhea (OR 0.4; 95% CI, 0.3-0.6), and H2 production (estimate -5.3, SE 0.7, P < 0.001). The effect on bloating was only significant in functional dyspepsia, irritable bowel syndrome-functional dyspepsia mixed type and functional abdominal pain/bloating (OR 0.1; 95% CI, 0.0-0.2; OR 1.7; 95% CI, 1.2-2.3 resp OR 4.4; 95% CI, 1.8-10.6). CONCLUSIONS: Significant effects on abdominal symptoms and H2 production by adding a test meal to LHBT in FGID patients are shown. Increased occurrence of nausea may be caused by gastric/duodenal hypersensitivity; decreased H2, diarrhea and borborygmi by slower and more physiologic gastric emptying resulting in later arrival of the test substance in the bowel. We recommend NCTs instead of LHBT to more physiologically represent FGID patients' meal-induced burden.

Better response to low FODMAP diet in disorders of gut-brain interaction patients with pronounced hydrogen response to a nutrient challenge test.

BACKGROUND AND AIM: Previous studies have shown a reduction of gastrointestinal symptoms in irritable bowel syndrome (IBS) patients following a low FODMAP diet (LFD). It remains unknown which disorders of gut-brain interaction (DGBI) patients would benefit most from LFD. We aimed to analyze LFD response regarding a preceding nutrient challenge test (NCT). METHODS: Data of 110 consecutive DGBI patients undergoing NCT and LFD between August 2015 and August 2018 were analyzed retrospectively. LFD response was assessed by changes in IBS Symptom Severity Score (IBS-SSS). In mixed-effects linear regression models, the impact of hydrogen values and abdominal symptoms during NCT, performed with 30-g lactulose and 400-mL liquid test meal, on IBS-SSS changes were analyzed. RESULTS: Low FODMAP diet induced a significant IBS-SSS reduction of 78 points (95% confidence interval [CI] 50-96; P < 0.001). Patients with higher NCT-induced hydrogen increase during proximal intestinal transit had a significantly better LFD response (-66 IBS-SSS reduction per 10-ppm hydrogen increase, 95% CI -129 to -4, P = 0.045). Additionally, the higher the NCT-induced maximum hydrogen increase during mid-distal and distal intestinal transit, the better are the responses to LFD (-6 IBS-SSS per 10-ppm maximum delta hydrogen, 95% CI -11 to -1, P = 0.040). There was no association of LFD response with abdominal symptom generation during NCT. CONCLUSIONS: Our study is the first one analyzing and demonstrating significant associations between NCT results and LFD response. These findings are of high clinical importance, as they identify a subgroup of DGBI patients that may profit most from a restrictive LFD as first-line therapy.

Increased visceral sensitivity, elevated anxiety, and depression levels in patients with functional esophageal disorders and non-erosive reflux disease.

BACKGROUND: Little is known about possible underlying psychological abnormalities and physiology of reflux hypersensitivity (RH) as defined in the recent Rome IV classification. We aimed to assess markers of psychological comorbidity as well as gastro-esophageal reflux measurements in RH patients compared to controls and also in patients with functional heartburn (FH) and non-erosive reflux disease (NERD) versus controls. METHODS: Data of 304 patients visiting our Functional Diagnostics Centre from 2016 to 2018 were analyzed. We focused on a psychological assessment using validated questionnaires (visceral sensitivity index; VSI, hospital anxiety and depression score; HADS) as well as multichannel intraluminal impedance (MII) and pH-metry data from the diagnostic work-up. KEY RESULTS: We found a decreased VSI of 57.8 ± 15.4 points (pts) among RH patients (n = 45) indicating higher visceral sensitivity compared to 85.7 ± 2.0 pts in the control group (n = 31, P < 0.001). Furthermore, a significant difference in VSI was found between the FH (60.8 ± 23.3 pts, n = 59, P < 0.001) and between the NERD (61.9 ± 20.8 pts, n = 67, P < 0.001) both compared to the control group. The HADS also displayed a significant difference between the RH (11.9 ± 6.0 pts, P < 0.001), FH (11.0 ± 7.4 pts, P < 0.001), respectively, NERD (11.3 ± 8.9 pts, P < 0.001) as compared to the control group (2.0 ± 1.4 pts). CONCLUSIONS AND INFERENCES: Increased sensation to visceral stimuli as well as anxiety and depression appears to play an important role not only in reflux hypersensitivity and functional heartburn as defined by Rome IV but also in NERD. These findings are in line with the disease concept of disorders of gut-brain interaction in which psychological comorbidities and visceral hypersensitivity play a major role.

Pyloric dilation with the esophageal functional lumen imaging probe in gastroparesis improves gastric emptying, pyloric distensibility, and symptoms.

BACKGROUND AND AIMS: The role of decreased pyloric distensibility in gastroparesis as measured by the endolumenal functional luminal imaging probe (EndoFLIP) has been receiving increasing attention. In this study, we present clinical outcomes to pyloric dilation with the esophageal FLIP (EsoFLIP) in regard to gastric emptying, symptom evolution, and FLIP metrics. METHODS: Patients evaluated for gastroparesis (gastric emptying studies of t1/2 ≥180 minutes during 13C-octanoic acid breath test and/or gastric remnants during gastroscopy after a sufficient fasting period) were scheduled for EsoFLIP controlled pyloric dilation. Pre- and postprocedural gastric emptying studies, questionnaires (Patient Assessment of Upper GI Symptoms Severity Index [PAGI-SYM; including the Gastroparesis Cardinal Symptom Index] and Patient Assessment of Quality of Life Index [PAGI-QOL]), and FLIP metrics were documented. Dilation was conducted according to a self-developed algorithm. RESULTS: Forty-six patients were analyzed (72% women; median age, 39 years [range, 18-88]). Etiologies of gastroparesis were diabetic in 10 patients (22%), idiopathic in 33 (72%), and postoperative in 3 (6%). Postprocedural gastric emptying time decreased from a median of 211 minutes to 179 minutes (P = .001). In accordance, pyloric distensibility, PAGI-SYM, PAGI-QOL, and Gastroparesis Cardinal Symptom Index values improved significantly. After a median follow-up of 3.9 months, 57% of all treated patients with returned questionnaires reported improved symptoms. CONCLUSIONS: Pyloric EsoFLIP controlled dilation shows value in the treatment of gastroparesis, both subjectively and objectively. Long-term follow-up to assess efficacy and comparative trials are warranted.

Nutrient Challenge Testing Is Not Equivalent to Scintigraphy-Lactulose Hydrogen Breath Testing in Diagnosing Small Intestinal Bacterial Overgrowth.

Background/Aims: Small intestinal bacterial overgrowth (SIBO) is a common condition in disorders of gut-brain interaction (DGBI). Recently, a combined scintigraphy-lactulose hydrogen breath test (ScLHBT) was described as an accurate tool diagnosing SIBO. We aim to analyze whether a lactulose nutrient challenge test (NCT), previously shown to separate DGBI from healthy volunteers, is equivalent to ScLHBT in diagnosing SIBO. Methods: We studied data of 81 DGBI patients undergoing ScLHBT with 30 g lactulose and 300 mL water as well as NCT with 30 g lactulose and a 400 mL liquid test meal. Differences in proportion of positive SIBO diagnoses according to specified cecal load and time criteria for NCT and ScLHBT, respectively, were tested in an equivalence trial. An odds ratio (OR) range of 0.80-1.25 was considered equivalent. Results: Diagnosis of SIBO during NCT was not equivalent to SIBO diagnosis in ScLHBT, considering a hydrogen increase before cecal load of 5.0%, 7.5%, or 10.0%, respectively ([OR, 3.76; 90% CI, 1.99-7.09], [OR, 1.87; 90% CI, 1.06-3.27], and [OR, 1.11; 90% CI, 0.65- 1.89]). Considering only time to hydrogen increase as criterion, the odds of a positive SIBO diagnosis in the NCT (0.65) was lower than in ScLHBT (1.70) (OR, 0.38; 90% CI, 0.23-0.65). Conclusions: This study could not show an equivalence of NCT and ScLHBT in diagnosing SIBO. A possible explanation might be the different transit times owing to unequal testing substances. The effect of this deviation in relation to consecutive therapy regimens should be tested in further prospective studies.

Short-term outcome after singular hydraulic EsoFLIP dilation in patients with achalasia: A feasibility study.

BACKGROUND: Achalasia is a chronic esophageal motility disorder characterized by impaired relaxation of the lower esophageal sphincter, determined by an elevated integrated relaxation pressure (IRP > 15 mm Hg) and absent peristalsis. Goal of treatment is facilitation of flow across the EGJ but minimizing postinterventional reflux. A new advanced hydraulic dilation technology, the esophageal functional luminal imaging probe (EsoFLIP), allows dynamic monitoring of hollow organ dimensions while performing hydraulic dilation. The aim of our study was to evaluate the treatment response after single EsoFLIP dilation in achalasia patients. METHODS: Dilation was performed under endoscopic control with the EsoFLIP device using a self-developed dilation algorithm. Symptom scores were assessed by the Eckardt score (ES) before and 1-4 weeks after intervention. Esophageal emptying before and after intervention was recorded with timed barium esophagogram. KEY RESULTS: We studied 28 consecutive untreated achalasia patients (8 female) with a median age of 43 years (range 19-82 years) undergoing their first dilation performed with the EsoFLIP, aiming at a maximum dilation diameter of 25 mm. Total ES was significantly reduced from 7 at baseline to 2 postintervention (P < .001). The median height of the barium column after 5 minutes was significantly reduced from 4.5 cm at baseline to 1.7 cm (P = .0087). No major complications occurred. CONCLUSIONS & INFERENCES: We found good efficacy in both subjective and objective short-term treatment outcome after singular EsoFLIP dilation in treatment-naive achalasia patients. Our findings suggest that EsoFLIP is a promising dilation technology that should be further studied in a larger, controlled setting with longer follow-up.

Endoscope presence during endoluminal functional lumen imaging probe (FLIP) influences FLIP metrics in the evaluation of esophageal dysmotility.

BACKGROUND: The functional lumen imaging probe (FLIP) system is an FDA-approved tool for dynamic evaluation of the esophagogastric junction (EGJ). Even though commercially available since 2009, FLIP utilization remains low, partly due to lack of consensus in methodology and interpretation. Therefore, we aimed to analyze the influence of concurrent endoscopy on FLIP measurements. METHODS: In this single-center study, we reviewed data from 93 patients undergoing FLIP for symptomatic esophageal motility disorders between 2016 and 2018. During sedated endoscopy, we measured luminal values (distensibility, cross-sectional area (CSA), and balloon pressure) at the EGJ and distal esophagus using 30, 40, and 50 mL distension volumes, with and without concurrent endoscope presence. All recorded values were compared at the various distension volumes between the two measurements using a Wilcoxon rank sum test. KEY RESULTS: There was a significant difference in distensibility and CSA with index distension volume (40 mL) at the EGJ comparing the two measurements: Lower median distensibility was 2.1 mm2  mm Hg-1 in the group with concurrent inserted endoscope, respectively, 3.4 mm2  mm Hg-1 without endoscope (P < .001), and median CSA was 86.0 resp. 110.0 mm2 (P < .001). No significant difference could be found in the measurements of the distal esophagus. CONCLUSIONS & INFERENCES: Our results show a significant difference in FLIP measurements with and without endoscope presence. This underlines the importance of establishing a consensus of a standardized FLIP protocol to define normal luminal values and guiding future FLIP diagnostic studies.

Opioid Treatment and Excessive Alcohol Consumption Are Associated With Esophagogastric Junction Disorders.

BACKGROUND/AIMS: The influence of external factors such as opioids and alcohol has been extensively investigated for various segments of the gastrointestinal tract. However, the association between their use and the development of esophagogastric junction outflow obstruction disorders (EGJOODs) is unknown. Therefore, the aim of this study is to analyze prevalence and clinical relevance of opioids and alcohol intake in patients with EGJOODs. METHODS: In this single-center, retrospective study, we reviewed clinical and pharmacological data of 375 consecutive patients who had undergone high resolution impedance manometry for EGJOODs. EGJOODs were classified according to the Chicago classification version 3.0 and to recently published normal values for test meals. Demographics, manometric data, and symptoms were compared between different groups using Pearson's chi-squared test, Fisher's exact test, and multivariate analysis. A P < 0.05 was considered significant. RESULTS: EGJOOD was found in 30.7% (115/375) of all analyzed patients. The prevalence of opioids (14.8% vs 4.2%, P = 0.026) was significantly higher in patients with EGJOODs compared to patients without EGJOODs. Additionally, excessive alcohol consumption (12.2% vs 3.5%, P = 0.011) was associated with EGJOODs. Excessive alcohol consumption was especially frequent in the non-achalasia esophagogastric junction outflow obstruction subgroup (16.2%) and opioid use in the achalasia type III subgroup (20.0%). CONCLUSIONS: We found a significant association between EGJOODs and opioid as well as excessive alcohol consumption. This underlines the importance of detailed history taking regarding medication and ethanol consumption in patients with dysphagia. Further prospective studies on mechanisms undelaying esophagogastric junction dysfunction due to opioids or alcohol are warranted.

Differentiation of functional gastrointestinal disorders from healthy volunteers by lactulose hydrogen breath test and test meal.

BACKGROUND AND AIM: Functional dyspepsia (FD) is a common disorder of gut-brain interaction with incompletely understood pathophysiology. Consequently, heterogeneous expert opinions on diagnostic tests and assessment of treatment efficacies exist. So far, no consensus about the most relevant diagnostic and outcome tool has been reached. In this study, we aimed to analyze the significance of a combined lactulose hydrogen breath test (LHBT) and liquid meal, yet representing a standardized test in irritable bowel syndrome (IBS), in FD. METHODS: We analyzed data of 146 FD, 204 IBS patients, and 50 healthy volunteers (HV). All patients underwent LHBT with a meal-drink consisting of 30-g Lactulose and 400-mL Ensure®. Effect of abdominal symptom generation in FD/IBS compared with HV was assessed on a patient-reported Likert-scale. RESULTS: There was a significant difference between FD/IBS patients and HV in LHBT-induced abdominal pain (odds ratio [OR] 246.9, 95% confidence interval [CI] 26.6-2290.7; OR 161.2, 95% CI 16.9-1534.8), abdominal bloating (OR 384.8, 95% CI 92.9-2135.4; OR 524.1, 95% CI 114.7-3432.3), borborygmi (OR 9.9, 95% CI 2.2-46.9; OR 17.7, 95% CI 4.7-67.4), nausea only in FD (OR 174.4, 95% CI 15.5-5375.5), and diarrhea in IBS only (OR 25.8, 95% CI 2.0-7012.6). Hydrogen production was not significantly different in FD/IBS and HV. CONCLUSIONS: In this study, we demonstrated significant differences in postprandial symptom generation in FD and IBS compared with HV after LHBT. This does not only allow us to discriminate FD/IBS from HV but may also represent a diagnostic and monitoring tool for FD/IBS in the future, including monitoring of treatment effects.