Lower prevalence of gastroesophageal reflux disease in patients with noncardiac chest pain on opiates: a cross-sectional study.

Opiates can cause heartburn and spastic esophageal dysmotility but their role in noncardiac chest pain (NCCP) is not known. Our aim was to characterize opiate effects on esophageal function using esophageal pH monitoring and high-resolution manometry (HREM) in these patients.We performed a cross sectional study of opiate users with NCCP who underwent HREM and esophageal pH study from 2010 to 2017 using opiate nonusers as a comparison group. Demographic data, symptoms, opiate use, endoscopic findings, esophageal pH study parameters, and HREM data were abstracted.Thirty three patients with NCCP on opiates were compared to 144 opiate non-users. Compared to opiate nonusers, opiate users had lower total acid exposure (2.3% vs. 3%, P = 0.012), lower upright acid exposure (1.2% vs. 3.1%, P = 0.032) and lower DeMeester score (6.5 vs. 12.7, P = 0.016). Opiate users also had higher lower esophageal sphincter integrated relaxation pressure (LES-IRP) (7.0 mm Hg [2.2, 11.7] vs. 3.7 mm Hg [1.1, 6.2] P = 0.011) and greater mean distal contractile integral (DCI) (2575 mm.Hg.s.cm [1134, 4466] vs. 1409 mm.Hg.s.cm [796, 3003] P = 0.03) than opiate non-users. The prevalence of hypertensive motility disorders (15.2% vs. 11.1%) and achalasia (12.1% vs. 2.1%) was higher in opiate users (P = 0.039) but did not reach significance on multivariate analysis.In patients presenting with NCCP, opiate users had lower esophageal acid exposure compared to opiate nonusers. This might be due to higher LES pressures preventing reflux and higher DCI leading to more rapid acid esophageal clearance.

Inpatient burden of esophageal cancer and analysis of factors affecting in-hospital mortality and length of stay.

Esophageal cancer (EC) continues to be a major source of morbidity and mortality in the United States. However, there has been a relative dearth of research into hospital utilization in patients with EC. This study examines temporal trends in hospital admissions, length of stay (LOS), mortality, and costs associated with EC. In addition, we also analyzed factors associated with inpatient mortality and LOS. We interrogated National Inpatient Sample (NIS), a large registry of inpatient data, to retrieve information about various demographic and factors associated with hospital stay in patients who were admitted for EC between the years 1998 and 2013 in the United States. After examining trends over time, multivariate analysis was performed to identify factors associated with LOS and mortality. During 1998-2013, 538,776 hospital stays with principal diagnosis of EC were reviewed. Number of hospital stays and inpatient charges increased by 397 per year (±67.8; P < 0.0001) and $3,033 per patient per year (±135; <0.0001) respectively. Mortality and LOS decreased by 0.23% per year (±0.03; P < 0.0001) and 0.07 days per year (±0.006; P < 0.0001) respectively. Multiple factors associated with LOS and mortality were outlined. Despite overall increase in hospital utilization with respect to number of admissions and inpatient charges, inpatient mortality and LOS associated with EC declined. Factors associated with inpatient mortality and LOS may help drive clinical decision-making and influence healthcare or hospital policy.

Association of sporadic and familial Barrett's esophagus with breast cancer.

Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC). Based on striking aggregation of breast cancer and BE/EAC within families as well as shared risk factors and molecular mechanisms of carcinogenesis, we hypothesized that BE may be associated with breast cancer. Pedigree analysis of families identified prospectively at multiple academic centers as part of the Familial Barrett's Esophagus Consortium (FBEC) was reviewed and families with aggregation of BE/EAC and breast cancer are reported. Additionally, using a matched case-control study design, we compared newly diagnosed BE cases in Caucasian females with breast cancer (cases) to Caucasian females without breast cancer (controls) who had undergone upper endoscopy (EGD). Two familial pedigrees, meeting a stringent inclusion criterion, manifested familial aggregation of BE/EAC and breast cancer in an autosomal dominant inheritance pattern with incomplete penetrance. From January 2008 to October 2016, 2812 breast cancer patient charts were identified, of which 213 were Caucasian females who underwent EGD. Six of 213 (2.82%) patients with breast cancer had pathology-confirmed BE, compared to 1 of 241 (0.41%) controls (P-value < 0.05). Selected families with BE/EAC show segregation of breast cancer. A breast cancer diagnosis is marginally associated with BE. We postulate a common susceptibility between BE/EAC and breast cancer.

A systematic review and meta-analysis of the relative efficacy and safety of treatment regimens for HIV-associated cerebral toxoplasmosis: is trimethoprim-sulfamethoxazole a real option?

OBJECTIVES: The objective of this study was to perform a systematic review and meta-analysis of the literature to evaluate the efficacy and safety of therapies for cerebral toxoplasmosis in HIV-infected adults. The pyrimethamine plus sulfadiazine (P-S) combination is considered the mainstay therapy for cerebral toxoplasmosis and pyrimethamine plus clindamycin (P-C) is the most common alternative treatment. Although trimethoprim-sulfamethoxazole (TMP-SMX) has potential advantages, its use is infrequent. METHODS: We searched PubMed and four other databases to identify randomized controlled trials (RCTs) and cohort studies. Two independent reviewers searched the databases, identified studies and extracted data. Risk ratios (RRs) were pooled across studies using random-effects models. RESULTS: Nine studies were included (five RCTs, three retrospective cohort studies and one prospective cohort study). In comparison to P-S, treatment with P-C or TMP-SMX was associated with similar rates of partial or complete clinical response [P-C: RR 0.87; 95% confidence interval (CI) 0.70-1.08; TMP-SMX: RR 0.97; 95% CI 0.78-1.21], radiological response (P-C: RR 0.92; 95% CI 0.82-1.03), skin rash (P-C: RR 0.81; 95% CI 0.56-1.17; TMP-SMX: RR 0.17; 95% CI 0.02-1.29), gastrointestinal impairment (P-C: RR 5.16; 95% CI 0.66-40.11), and drug discontinuation because of adverse events (P-C: RR 0.32; 95% CI 0.07-1.47). Liver impairment was more frequent with P-S than P-C (P-C vs. P-S: RR 0.48; 95% CI 0.24-0.97). CONCLUSIONS: The current evidence fails to identify a superior regimen in terms of relative efficacy or safety for the treatment of HIV-associated cerebral toxoplasmosis. Use of TMP-SMX as preferred treatment may be consistent with the available evidence and other real-world considerations. Larger comparative studies are needed.

Obesity-related insulin resistance in adolescents: a systematic review and meta-analysis of observational studies.

Insulin resistance is common among obese adolescents; however, the extent of this problem is not clear. We conducted a systematic review of PubMed-Medline, CINAHL, The Web of Science, EMBASE and Scopus for observational studies evaluating components defining insulin resistance (insulin, C-peptide and homeostatic model assessment-insulin resistance [HOMA-IR]) in obese adolescents (12-18 years) versus non-obese adolescents. Our systematic review and meta-analysis followed the PRISMA guidelines. Data were combined using a random-effects model and summary statistics were calculated using the mean differences (MDs). 31 studies were included (n = 8655). In 26 studies, fasting insulin levels were higher in obese adolescents when compared to non-obese adolescents (MD = 64.11 pmol/L, 95%CI 49.48-78.75, p < 0.00001). In three studies, fasting C-peptide levels were higher in obese adolescents when compared to non-obese adolescents (MD = 0.29 nmol/L, 95%CI 0.22-0.36, p < 0.00001). In 24 studies, HOMA-IR values were higher in obese adolescents when compared to non-obese adolescents (MD = 2.22, 95%CI 1.78-2.67, p < 0.00001). Heterogeneity of effects among studies was moderate to high. Subgroup analyses showed similar results to the main analyses. Circulating insulin and C-peptide levels and HOMA-IR values were significantly higher in obese adolescents compared to those non-obese.

Spectrum of esophageal dysmotility in systemic sclerosis on high-resolution esophageal manometry as defined by Chicago classification.

The classic manometric findings in systemic sclerosis are aperistalsis of the esophageal body with hypotensive lower esophageal sphincter. These changes contribute to gastroesophageal reflux disease in these patients. With widespread use of high-resolution esophageal manometry, diverse abnormalities are seen. The aim of this study is to characterize esophageal dysmotility in patients with systemic sclerosis undergoing high-resolution esophageal manometry and compare demographic features and diagnostic test results among patients with varying degrees of esophageal dysmotility. Patients with systemic sclerosis who underwent high-resolution esophageal manometry between January 2008 and October 2014 at our institution were identified. High-resolution esophageal manometry studies were reinterpreted using the Chicago Classification, v3.0 criteria. We also reviewed the patient charts for demographic data, indications for manometry, esophagogastroduodenoscopy findings, pH studies, medication use, and autoantibody panel. The cohort consisted of 122 patients with a mean age of 53.3 ± 15.3 years. High-resolution esophageal manometry was normal in 23, showed ineffective esophageal motility in 22, absent contractility in 73, and one case each of type II achalasia, esophagogastric junction outflow obstruction, hypercontractile esophagus, and distal esophageal spasm. Patients with absent contractility were younger and more likely to have erosive esophagitis, hiatal hernia, and esophageal strictures than patients with ineffective esophageal motility or normal manometry. There were no statistically significant differences in the groups based on autoantibodies or indications for manometry. Diverse esophageal motility abnormalities were noted in systemic sclerosis with ineffective esophageal motility or absent contractility observed in over three-fourth of the patients. Patients with absent contractility were younger and had more severe reflux. The severity of gastroesophageal reflux disease related endoscopic findings correlated with the degree of esophageal dysmotility on high-resolution esophageal manometry.

Use of a positional therapy device significantly improves nocturnal gastroesophageal reflux symptoms.

The aim of this study was to measure the efficacy of a positional therapy device (PTD) at reducing proton pump inhibitor (PPI) refractory nocturnal GERD symptoms. Among patients with GERD, nocturnal symptoms are very common. A recent study demonstrated a decrease in nocturnal acid exposure and reflux episodes in healthy volunteers who slept using a PTD. This is a single-center prospective trial involving patients on anti-secretory medications with continued nocturnal heartburn and regurgitation. Patients completed the Nocturnal GERD Symptom Severity and Impact Questionnaire (N-GSSIQ) and GERD health-related quality of life questionnaire (GERD-HRQL) at enrollment. Patients were instructed to sleep on the PTD for at least 6 hours a night during the two week study period; subjects continued their baseline anti-secretory medication dose. After 2 weeks, the questionnaires were repeated. A total of 27 patients (16 females and 11 males; age 57.8 ± 15.1) were recruited. After 2 weeks of PTD use, N-GSSIQ scores significantly improved from baseline, with a mean total score improvement of 39.5 (mean 57.7 [pre] vs. 18.2 [post], P < 0.001). Significant improvement from baseline was also observed for the GERD-HRQL questionnaire (29.8 vs. 16.7, P < 0.001). No adverse events were reported. At 3 months after the trial period, 91% of the subjects continued to use the PTD on a nightly basis. Use of the PTD significantly decreased nocturnal GERD symptoms and improved GERD-HRQL. The PTD was well tolerated during the study period and for 3 months after enrollment.

Higher visceral to subcutaneous fat ratio is associated with small intestinal bacterial overgrowth.

BACKGROUND AND AIMS: There is a lack of studies evaluating the association between small intestinal bacterial overgrowth (SIBO) and abdominal fat. The aim of this study was to evaluate whether visceral fat area (VFA), subcutaneous fat area (SFA) or visceral to subcutaneous fat ratio (VFA/SFA ratio) were associated with SIBO. METHODS AND RESULTS: In this case-control study, 152 eligible patients submitted to glucose hydrogen/methane breath test who also had computed tomography (CT) of the abdomen performed were included. Clinical and demographic information was obtained. VFA and SFA were measured using Image J software at lumbar 3 level on CT cross-sectional image of the 152 patients included in this study, 68 patients (44.7%) tested positive for SIBO. In the univariate analysis, the presence of SIBO was associated with older age (65.2 ± 1.5 vs. 59.3 ± 1.5, p = 0.007); type 2 diabetes mellitus (33.8% vs. 17.9%; p = 0.019); hypertension (63.2% vs. 39.3%; p = 0.003); metabolic syndrome (85.3% vs. 64.3%; p = 0.003); and higher VFA/SFA ratio (1.0 ± 0.1 vs. 0.7 ± 0.1; p < 0.001). In multivariate analysis, metabolic syndrome (odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.1-5.7; p = 0.035) and higher VFA/SFA ratio (OR: 3.3; 95% CI: 1.6-7.2; p = 0.002) remained independently associated with SIBO. CONCLUSION: The presence of SIBO was found to be associated with high VFA/SFA ratio measured from cross-sectional CT image.

Timed barium esophagram in achalasia types.

Relationships of timed barium esophagram (TBE) findings to achalasia types defined by high-resolution manometry (HRM) have not been elucidated. Therefore, we correlated preoperative TBE and HRM measurements in achalasia types and related these to patient symptoms and prior treatments. From 2006 to 2013, 248 achalasia patients underwent TBE and HRM before Heller myotomy. TBE height and width were recorded at 1 and 5 minutes; HRM measured lower esophageal sphincter mean basal pressure, integrated relaxation pressure (IRP), and mean esophageal body contraction amplitude. Achalasia was classified into types I (25%), II (65%), and III (9.7%). TBE height at 5 minutes was higher for I (median 8 cm; interquartile range 6-12) and II (8 cm; 8-11) than for III (1 cm; 0-7). TBE width at 5 minutes was widest (3 cm; 2-4), narrower in II (2 cm; 2-3), and narrowest in I (1 cm; 0-2), P < 0.001. Volume remaining at 1 and 5 minutes was lower in III (1 m(2) ; 0-16) than I (42 m(2) ; 17-106) and II (39 m(2) ; 15-60), highlighting poorer emptying of I and II. Increasing TBE width correlated with deteriorating morphology and function from III to II to I. Symptoms poorly correlated with TBE and HRM. Prior treatment was associated with less regurgitation, faster emptying, and lower IRP. Although TBE and HRM are correlated in many respects, the wide range of their measurements observed in this study reveals a spectrum of morphology and dysfunction in achalasia that is best characterized by the combination of these studies.

Role of wireless motility capsule in the assessment and management of gastrointestinal dysmotility in patients with diabetes mellitus.

BACKGROUND: Gastrointestinal (GI) dysmotility is common in diabetic patients. Wireless Motility Capsule (WMC) provides the transit profile of the entire GI tract in a single study. Factors affecting GI dysmotility and utility of WMC study are not clearly established in diabetic patients. Our aims were to study the pattern of GI dysmotility using WMC and evaluate the effect of glycemic control and presence of diabetic microvascular complications on motility impairment in diabetic patients. We also assessed the impact of WMC findings on clinical management. METHODS: Retrospective chart review of all diabetic patients who underwent WMC testing at our institution from 2010 to 2015 was performed. Demographics, hemoglobinA1c levels, microvascular complications, and WMC findings were obtained. Impact of WMC on clinical management was assessed. KEY RESULTS: A total of 100 patients were included. Mean age was 45±19 years and 76% were female. Seventy-two percentage had abnormal WMC testing, of which 29 (40%) had multiregional dysmotility. There were no significant differences in demographics, diabetic microvascular complications or hemoglobinA1c levels among patients with normal and abnormal WMC testing or among patients with isolated vs multiregional dysmotility. Information about subsequent clinical management was available for 47 patients. WMC testing was abnormal in 33 (70%) patients and treatment changes based on WMC results were made in 24 patients (73%). CONCLUSIONS & INFERENCES: There was no association between hemoglobinA1c levels, microvascular complications and pattern of GI dysmotility in diabetic patients undergoing WMC. WMC testing lead to management changes in approximately 75% of diabetic patients with GI dysmotility.

A randomized prospective trial comparing unsedated esophagoscopy via transnasal and transoral routes using a 4-mm video endoscope with conventional endoscopy with sedation.

BACKGROUND AND STUDY AIMS: Unsedated upper endoscopy is an attractive alternative to conventional sedated endoscopy because it can reduce the cost, complications, and recovery time of the procedure. However, it has not gained widespread acceptance in the United States. A prototype 4-mm-diameter video esophagoscope is available. Our aims were to compare unsedated esophagoscopy using this 4-mm esophagoscope with conventional sedated endoscopy with regard to diagnostic accuracy and patient tolerance, to determine the optimal intubation route (transnasal vs. transoral), and to identify the predictors of tolerance of unsedated endoscopy. PATIENTS AND METHODS: Outpatients presenting for conventional endoscopy were randomized to undergo unsedated esophagoscopy by either the transnasal or the transoral route, followed by conventional endoscopy. The diagnostic findings, optical quality, and patient tolerance scores were assessed. RESULTS: A total of 137 patients were approached and 90 (65.6 %) were randomized to undergo esophagoscopy by the transnasal route (n = 44) or by the transoral route (n = 46) before undergoing conventional esophagoscopy. Patient tolerance of unsedated esophagoscopy was comparable to that of conventional endoscopy. The transnasal route was better tolerated than the transoral route, except with respect to pain, and 93.2 % in transnasal group and 91.3 % in transoral group were willing to have the procedure again. The diagnostic accuracy of endoscopy using the 4-mm video endoscope was similar to that of standard endoscopy. Patients who tolerated the procedure well had lower preprocedure anxiety scores (29 vs. 42.5, P = 0.021) and a higher body mass index (31.5 kg/m2 vs. 28 kg/m2, P = 0.029) than the other patients. CONCLUSIONS: Unsedated esophagoscopy with a 4-mm esophagoscope was well tolerated and has a level of diagnostic accuracy comparable to that of conventional endoscopy. Factors associated with good tolerance of unsedated esophagoscopy were low anxiety levels, high body mass index, and use of the transnasal route. Unsedated endoscopy may be offered to a selected group of patients based on these criteria.