Crowell, Michael D.

Abstract Background Baseline impedance measured with ambulatory impedance pH monitoring ( MII ‐pH) and a mucosal impedance catheter detects gastroesophageal reflux disease ( GERD ). However, these tools are limited by cost or patient tolerance. We investigated whether baseline impedance measured during high‐resolution impedance manometry ( HRIM ) distinguishes GERD patients from controls. Methods Consecutive patients with clinical HRIM and MII ‐pH testing were identified. Gastroesophageal reflux disease was defined by esophageal pH <4 for ≥5% of both the supine and total study time, whereas controls had an esophageal pH <4 for ≤3% of the study performed off PPI . Baseline impedance was measured over 15 seconds during the landmark period of HRIM and over three 10 minute intervals during the overnight period of MII ‐pH. Key Results Among 29 GERD patients and 26 controls, GERD patients had a mean esophageal acid exposure time of 22.7% compared to 1.2% in controls ( P <.0001). Mean baseline impedance during HRIM was lower in GERD (1061 Ω) than controls (2814 Ω) ( P <.0001). Baseline mucosal impedance measured during HRIM and MII ‐pH correlated ( r =0.59, P <.0001). High‐resolution esophageal manometry baseline impedance had high diagnostic accuracy for GERD , with an area under the curve ( AUC ) of 0.931 on receiver operating characteristics ( ROC ) analysis. A HRIM baseline impedance threshold of 1582 Ω had a sensitivity of 86.2% and specificity of 88.5% for GERD , with a positive predictive value of 89.3% and negative predictive value of 85.2%. Conclusions & Inferences Baseline impedance measured during HRIM can reliably discriminate GERD patients with at least moderate esophageal acid exposure from controls. This diagnostic tool may represent an accurate, cost‐effective, and less invasive test for GERD .

Background and Aims: Gastroparesis (GP) patients suffer from recurrent symptoms of nausea, vomiting, early satiety, and abdominal pain. The impact of GP on quality of life (QoL), health care utilization and daily activities is not well understood. Materials and Methods: Part 1: 398 adult patients (≥18 y) with documented GP (symptoms >6 mo) were surveyed to assess QoL and pain using the Short Form 36 and McGill pain questionnaires. Part 2: 491 adult GP patients were surveyed to evaluate employment status, work and daily activities, medication use, physician visits, diagnostic testing, emergency room visits, and hospitalizations related to their GP symptoms. Both protocols received Institutional Review Board approval. Results: Part 1: 250 fully evaluable surveys were returned (63%). The mean age was 46.8 years (range, 18 to 84 y); 78% were women. Mean Short Form 36 scores for mental health (56.9) and social functioning (68.1) were analogous to scores for patients with serious chronic medical disorders and depression. Pain scores were lower in patients with idiopathic GP compared with diabetic GP. Part 2: 228 evaluable surveys were analyzed (58.3% response rate). The mean age was 49.6 (19 to 86 y); 77.2% were women. GP symptoms reduced daily activities in 67.5% and lowered annual income in 28.5%. In total, 11% were disabled due to GP symptoms. Conclusions: GP reduces patients’ QoL and places a significant financial burden on the health care system. Treatment strategies for GP patients should be broad based and incorporate pain management, psychological evaluation and management, and strategies to improve overall well-being with a return to work and daily activities.

AbstractBackgroundSymptoms suggestive of gastroparesis are non‐specific and conflicting reports exist regarding the ability of symptoms to predict the presence of gastroparesis. Our aim, therefore, was to evaluate the relationships between gastroparetic symptoms and their impact on quality of life and determine their relationship with clinical factors and gastric emptying.MethodsGastric emptying scintigraphy, sociodemographic features, health care resource utilization, gastroparetic symptoms, and quality of life using validated questionnaires were obtained from consecutive patients referred for gastric emptying testing (GET). Descriptive analyses were conducted and logistic regression was performed to evaluate associations with abnormal gastric emptying after controlling for other covariates.Key ResultsTwo hundred and sixty‐six patients participated (195 females; mean age, 49.1 ± 17.6 years); 75% met Rome III criteria for functional dyspepsia. Gastric emptying was delayed in 28.2% at 4 h; the delay was mild in 48%, moderate in 20% and severe in 32%. Nausea/emesis and postprandial fullness, but not bloating, were significantly greater in those with delayed emptying. Postprandial fullness was most severe. Weak correlations were identified between symptom severity and the severity of gastric emptying delay. Quality of life was also lower in the delayed emptying group. Logistic regression analysis demonstrated associations between delayed gastric emptying and lower quality of life and increased symptom severity.Conclusions & InferencesIn patients referred for GET, gastroparetic symptoms were more severe in those with delayed emptying. A decrease in quality of life in those with delayed gastric emptying was also present; this was not related to the severity of the delay in gastric emptying.

AbstractBackgroundThere have been conflicting results from studies that have evaluated psychological disturbances in functional dyspepsia (FD). We conducted a comprehensive survey of psychological measures in patients undergoing gastric emptying testing (GET) in order to determine the relationship among psychological distress, gastric emptying, and dyspeptic symptoms.MethodsConsecutive patients referred for GET were prospectively enrolled. Details regarding patient characteristics, health care utilization, dyspeptic symptoms, quality of life, and psychological dysfunction were obtained. Depression, anxiety, somatization, stress, positive and negative affect, and alexithymia were queried using validated questionnaires. We compared those dyspeptic patients who met Rome III criteria for FD to those who did not meet these criteria.Key ResultsTwo hundred and nine patients (160 female; mean age 46.6 years ± 17.3 years) participated. Around 151 patients (72%) met Rome III criteria for FD. In the entire group, a high level of depression, anxiety, somatization, and perceived stress was present compared to population norms. Health care seeking behavior and symptom severity were greater in those with FD and quality of life was lower compared to non‐FD. Gastric emptying did not differentiate the two groups and similar degrees of psychological distress were present whether emptying was delayed or normal.Conclusions & InferencesIn patients referred for GET, substantial psychological distress is present. The degree of distress was similar regardless of whether the patient met Rome III FD criteria or not. Further evaluation of psychological dysfunction in FD patients may lead to improved diagnosis and determination of the most appropriate treatment.

SummaryBackgroundObesity is associated with increased oesophageal acid exposure time (AET) in patients with gastro‐oesophageal reflux (GER), and may decrease the effects of proton pump inhibitors (PPIs).AimTo evaluate the effects of increased body mass on the ability of PPI therapy to decrease AET in patients with reflux symptoms.MethodsAcid exposure time profiles collected from adult patients using wireless pH‐metry while on or off PPI therapy was retrospectively reviewed. Patients were separated into five body mass index (BMI) categories as defined by the World Health Organization. A multivariable logistic regression evaluated the association between abnormal AET and BMI groups while controlling for age, gender and pH capsule placement methods.ResultsThe study group comprised 968 patients with 336 (34.7%) studied on a PPI and 632 (65.3%) studied off PPI therapy. AET (total greater than 5.3%) was found more frequently in the overweight (67%) and obese classes (74–80%) compared to those who were normal weight (40%) while off acid‐suppressing medications (P < 0.001). No significant differences were found between these groups when studied on acid‐suppressing medications, and the proportion of patients with abnormal AET across BMI classes was similar regardless of taking a PPI either once or twice daily.ConclusionsThis is the largest study to report on the relationship between BMI and oesophageal acid exposure time in patients with GER on and off PPI therapy. We conclude that obesity is related to increased acid exposure time, but with no significant difference in acid exposure time among different weight‐based groups when taking a once or twice‐daily PPI.

Background: Systemic sclerosis (SSc) patients with gastrointestinal (GI) involvement have a lower quality of life (QoL) and while the impact of upper GI symptoms on QoL in SSc patients has been described few data exist on the presence and impact of lower gastrointestinal (LGI) and pelvic floor symptoms in SSc. Our goal was to assess the prevalence of these symptoms in women with SSc and evaluate their impact on QoL. A secondary hypothesis was that the impact of LGI symptoms on QoL is mediated by depression. Study: Women with SSc (n=175) attending an outpatient scleroderma clinic completed multiple validated questionnaires. Pelvic floor and LGI symptoms included fecal incontinence (FI), urinary incontinence (UI), dual incontinence (DI), chronic constipation, diarrhea, and pelvic pain. The Student t tests adjusted for multiple comparisons were used to evaluate group differences at the 0.05 level. Results: Complete data were available for 160 women. FI was reported by 65, UI by 64, DI by 40, chronic constipation by 94, diarrhea by 82, and pelvic pain by 35 of SSc patients. Overall QoL was reduced in SSc patients with FI (0.96 vs. 0.63; P=0.007), UI (0.96 vs. 0.65; P=0.01), DI (1.11 vs. 0.67; P=0.002), and pelvic pain (1.01 vs. 0.70; P=0.04). Antidepressant use was reported by 26%. The negative impact on QoL in patients with pelvic floor symptoms was partially mediated by depression. Conclusions: Women with SSc suffer from an increased prevalence of LGI and pelvic floor symptoms including FI, UI, diarrhea, constipation, and pelvic pain and this effect seems to be partially mediated by depression.

Duodenal aspirates are not commonly collected, but they can be easily used in detection of small intestinal bacterial overgrowth (SIBO). Proton pump inhibitor (PPI) use has been proposed to contribute to the development of SIBO. We aimed to determine the yield of SIBO-positive cultures detected in duodenal aspirates, the relationship between SIBO and PPI use, and the clinical outcomes of patients identified by this method. In a retrospective study, we analyzed electronic medical records from 1263 consecutive patients undergoing upper endoscopy at a tertiary medical center. Aspirates were collected thought out the third and fourth portions of the duodenum, and cultures were considered to be positive for SIBO if they produced more than 100,000 cfu/mL. Culture analysis of duodenal aspirates identified SIBO in one-third of patients. A significantly higher percentage of patients with SIBO use PPIs than patients without SIBO, indicating a possible association. Similar proportions of patients with SIBO improved whether or not they received antibiotic treatment, calling into question the use of this expensive therapy for this disorder.

AbstractBackgroundGastroesophageal reflux plays an important role in chronic cough (CC). Whether disturbed esophageal motility contributes to increased esophageal reflux exposure or interferes with swallowed bolus clearance is unclear. This study used high resolution esophageal manometry and impedance (HRIM) together with Chicago Classification, and 24‐h impedance pH (MII/pH) to address these questions in patients with CC compared with heartburn (HB).MethodsA retrospective review of 32 patients with CC (mean age 57 [95% CI: 52–62] years) and 32 patients with symptoms of HB (55 [52–62] years) referred for HRIM and MII/pH between September 2012 and September 2013 was undertaken.Key ResultsWeak peristalsis with large breaks (WPLBs) was observed in 34% of CC patients compared with only 12% of HB patients (p = 0.027). Pathological acid exposure time (AET) was identified in 81% of CC patients with WPLBs compared with 29% without (p = 0.011). Increased AET was associated with prolonged clearance time of refluxed events (p = 0.006) rather than increased number of events. AET correlated with the percentage of peristaltic events with large breaks in CC (ρ = 0.467, p = 0.007). Similar data were obtained for total bolus (acid and non‐acid) exposure time. Only one of the CC patients with WPLBs exhibited complete bolus transit (CBT) on swallowing compared with 81% without WPLBs (p < 0.001). Moreover, the percentage of peristaltic events associated with CBT negatively correlated with the percentage of peristaltic events with large breaks (r = −0.653, p < 0.001) in CC.Conclusions & InferencesOne‐third of CC patients exhibit WPLBs, which directly impacts on clearance of refluxed events and bolus's swallowed. These observations may have important implications for esophageal‐bronchial interaction in CC.

Background and aims Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators. Methods We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1β and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat. Results NCs had higher fatty acids, IL-8 and IL-1β versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat. Conclusions UFAs, IL-1β and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP.

ABSTRACTObjectives:We evaluated eating behaviors and quality of life (QOL) in preadolescent children at risk for obesity, with and without abdominal pain (AP).Methods:Participants were parent–child dyads enrolled in a randomized, controlled obesity prevention trial. The children were between 5 and 10 years of age and at risk for obesity (70th–95th percentile of body mass index, n = 420). Parents completed measures of their child's eating behaviors, QOL, AP, and bowel function and their own depression status, concern about child weight, and feeding practices. Children's height and weight were also measured.Results:Children with frequent AP (≥2/month, n = 103) were compared with children reporting infrequent AP (<2/month, n = 312). Age and body mass index did not differ between groups, but AP was more prevalent in girls. Child emotional overeating and parental depression scores were higher in the frequent AP group (P < 0.01), and child QOL was lower (P < 0.01). In multivariable analysis, female gender (odds ratio [OR] 2.18, 95% confidence interval [CI] 1.20–3.97), emotional overeating (OR 2.28, 95% CI 1.37–3.81), and parental depression (OR 1.23, 95% CI 1.12–1.35) were associated with more frequent AP. Secondary analyses were completed for children who met Rome III criteria for irritable bowel syndrome.Conclusions:Clinicians working with children with AP at risk for obesity should consider assessing for and, when appropriate, addressing parent and child factors that could exacerbate AP.