Clovis organizational dynamics at a Late Glacial campsite in the central Great Lakes: Belson site excavations 2020-2021.

The Belson site is located on an outwash plain draining the Early Algonquin stage of the central Great Lakes (coinciding with the Older Dryas stadial period around 14,000 Cal B.P) southwest across Lower Michigan into the Ohio tributaries. By 13,000 Cal B.P the St. Joseph River had incised multiple channels into this plain. On a terrace just north of a now-abandoned channel, a detailed surface study by Talbot from 2005-2018 showed several flake clusters largely of Attica chert, procured about 235 km southwest of Belson. A study of the surface sample was published by the authors in 2021 and indicated that the points were made with the Clovis technological pattern. Excavations in 2020-21 revealed hundreds of buried flakes and multiple tools in the lower, less-disturbed terrace sediment. Plotting of this material indicates successive occupations below the ploughed deposit and covering more than 30 m2. The buried assemblages are similar to the published surface assemblage with the addition of more small scrapers and manufacturing debris. Several of the buried tools have traces of proteins from a range of mammals, suggesting a broad-spectrum subsistence strategy. The documentation of a succession of little disturbed deposits with precisely recorded micro-debris will allow for testing of models describing settlement choice and developing dynamics of internal site organization. Initial analysis of recovered data provides support for an 'outcrop centered' model where high-quality chert outcrops serve as central places on the landscape. Samples of sediment and charcoal for identification and dating await study.

Tailored Treatment Based on Helicobacter pylori Genetic Markers of Resistance Is Associated With Higher Eradication Success.

INTRODUCTION: Increasing antimicrobial resistance with Helicobacter pylori infection has focused efforts to tailor eradication therapy based on identifying genetic markers of resistance to predict antimicrobial susceptibility. METHODS: In this retrospective study, we report the effect of routine inclusion of antimicrobial susceptibility testing and recommendations for eradication therapy with gastric specimens with H. pylori . RESULTS: The use of a recommended treatment regimen based on genetic markers of resistance was associated with an 84% rate of eradication success and 4.4 greater odds of eradication relative to unrecommended treatment. DISCUSSION: This is the first study describing the use of H. pylori genetic resistance testing as standard of care.

Coefficient of Fat Absorption to Measure the Efficacy of Pancreatic Enzyme Replacement Therapy in People With Cystic Fibrosis: Gold Standard or Coal Standard?

OBJECTIVES: We sought data on the validity, reliability, responsiveness, and feasibility of the coefficient of fat absorption (CFA) as a measure of pancreatic enzyme replacement therapy (PERT) efficacy in people with cystic fibrosis (pwCF) and reviewed the literature for alternative measures. METHODS: We searched PubMed for the Medical Subject Heading cystic fibrosis and the key words cystic fibrosis, fat absorption, CFA, and fecal fat imbalance; historical articles; and citations in bibliographies. RESULTS: The lower the CFA, the greater its variability; thus, it is less variable in healthy individuals who have higher CFA than pwCF. In addition, the test-retest values for CFA are more variable in pwCF than the general population. There is no correlation between CFA and body mass index or PERT dose but CFA is related to gastrointestinal signs and symptoms. Research-quality CFA studies are expensive, time consuming, and odious to pwCF and research staff. Sparse stool tests, breath tests, and blood tests of fat absorption have been studied as potential alternatives to CFA to measure PERT efficacy. CONCLUSIONS: Based on the evidence, we conclude that CFA as a measure of the efficacy of PERT is more of a "coal standard" than a gold standard; developing suitable alternatives should be a priority.

Incidence of sedation-related adverse events during ERCP with anesthesia assistance: a multicenter observational study.

BACKGROUND AND AIMS: Anesthesia assistance is commonly used for ERCP. General anesthesia (GA) may provide greater airway protection but may lead to hypotension. We aimed to compare GA versus sedation without planned intubation (SWPI) on the incidence of hypoxemia and hypotension. We also explored risk factors for conversion from SWPI to GA. METHODS: This observational study used data from the Multicenter Perioperative Outcomes Group. Adults with American Society of Anesthesiologists physical status class I to IV undergoing ERCP between 2006 and 2019 were included. We compared GA and SWPI on incidence of hypoxemia (oxygen saturation <90% for ≥3 minutes) and hypotension (mean arterial pressure <65 mm Hg for ≥5 minutes) using joint hypothesis testing. The association between anesthetic approach and outcomes was assessed using logistic regression. The noninferiority delta for hypoxemia and hypotension was an odds ratio of 1.20. One approach was deemed better if it was noninferior on both outcomes and superior on at least 1 outcome. To explore risk factors associated with conversion from SWPI to GA, we constructed a logistic regression model. RESULTS: Among 61,735 cases from 42 institutions, 38,830 (63%) received GA and 22,905 (37%) received SWPI. The GA group had 1.27 times (97.5% confidence interval, 1.19-1.35) higher odds of hypotension but .71 times (97.5% confidence interval, .63-.80) lower odds of hypoxemia. Neither group was noninferior to the other on both outcomes. Conversion from SWPI to GA occurred in 6.5% of cases and was associated with baseline comorbidities and higher institutional procedure volume. CONCLUSIONS: GA for ERCP was associated with less hypoxemia, whereas SWPI was associated with less hypotension. Neither approach was better on the combined incidence of hypotension and hypoxemia.

Receipt of Serial Endoscopy Procedures Prior to Esophageal Adenocarcinoma Diagnosis Is Associated with Better Survival.

BACKGROUND: The poor prognosis of esophageal adenocarcinoma (EAC) has focused efforts on early detection by serial endoscopic surveillance of Barrett's esophagus (BE). Previously, we reported that receipt of endoscopy before EAC diagnosis was associated with improved survival. AIM: We aimed to refine our previous analysis, assessing surveillance as measured by performance of serial endoscopy before EAC diagnosis and evaluating its association with stage and survival. METHODS: A retrospective cohort study was performed using the Surveillance, Epidemiology and End Results-Medicare database. Patients aged ≥ 70 years with EAC diagnosed during 1998-2009 were identified. Diagnosis with BE and receipt of ≥ 2 upper endoscopic procedures within 5 years before cancer diagnosis were identified. We compared a reference group not receiving serial endoscopy to 3 patterns based on ≥ 2 endoscopy dates relative to a timepoint 2 years before cancer diagnosis: "remote," "recent," and "sustained." RESULTS: Among 5532 patients, 28% (n = 1,575) had localized stage. Thirteen percent (n = 703) received ≥ 2 endoscopic procedures before cancer diagnosis: 224, 298, and 181 in the "recent," "remote," and "sustained" groups. Serial endoscopy and prior BE were associated with localized stage ("sustained" group OR 2.95, 95% confidence interval [CI] 2.07, 4.19; prior BE OR 2.68, 95% CI 2.03, 3.56). Serial endoscopy was associated with improved survival even with adjustment for lead time bias ("sustained" group HR 0.45, 95% CI 0.37, 0.55) and length time bias. CONCLUSIONS: Sustained endoscopy was associated with earlier stage and improved survival. These results support the role of sustained surveillance in early detection of EAC.

The Intestinal Microbiome and Cystic Fibrosis Transmembrane Conductance Regulator Modulators: Emerging Themes in the Management of Gastrointestinal Manifestations of Cystic Fibrosis.

PURPOSE OF REVIEW: While commonly associated with pulmonary manifestations, cystic fibrosis (CF) is a systemic disease with wide-ranging effects on the gastrointestinal (GI) tract. This article reviews major recent updates in gastroenterological CF care and research. RECENT FINDINGS: The high burden of GI symptoms in CF has led to recent studies assessing GI-specific symptom questionnaires and scoring systems. Intestinal dysbiosis potentially contributes to gastrointestinal symptoms in patients with CF and an increased risk of gastrointestinal cancers in CF. An increased incidence of colorectal cancer (CRC) has led to CF-specific CRC screening and surveillance recommendations. Pharmacologic therapies targeting specific cystic fibrosis transmembrane conductance regulator (CFTR) mutations have shown promise in treating GI manifestations of CF. New research has highlighted the importance of intestinal dysbiosis in CF. Future studies should assess whether CFTR modulators affect the gut microbiome and whether altering the gut microbiome will impact GI symptoms and GI cancer risk.

Effects of spatially-varying substrate anchoring on instabilities and dewetting of thin nematic liquid crystal films.

Partially wetting nematic liquid crystal (NLC) films on substrates are unstable to dewetting-type instabilities due to destabilizing solid/NLC interaction forces. These instabilities are modified by the nematic nature of the films, which influences the effective solid/NLC interaction. In this work, we focus on the influence of imposed substrate anchoring on the instability development. The analysis is carried out within a long-wave formulation based on the Leslie-Ericksen description of NLC films. Linear stability analysis of the resulting equations shows that some features of the instability, such as emerging wavelengths, may not be influenced by the imposed substrate anchoring. Going further into the nonlinear regime, considered via large-scale GPU-based simulations, shows however that nonlinear effects may play an important role, in particular in the case of strong substrate anchoring anisotropy. Our simulations show that instability of the film develops in two stages: the first stage involves formation of ridges that are perpendicular to the local anchoring direction; and the second involves breakup of these ridges and formation of drops, whose final distribution is influenced by the anisotropy imposed by the substrate. Finally, we show that imposing more complex substrate anisotropy patterns allows us to reach basic understanding of the influence of substrate-imposed defects in director orientation on the instability evolution.

Inactivation of CFTR by CRISPR/Cas9 alters transcriptional regulation of inflammatory pathways and other networks.

BACKGROUND: Individuals with cystic fibrosis (CF) experience elevated inflammation in multiple organs, but whether this reflects an inherent feature of CF cells or is a consequence of a pro-inflammatory environment is not clear. METHOD: Using CRISPR/Cas9-mediated mutagenesis of CFTR, 17 subclonal cell lines were generated from Caco-2 cells. Clonal lines with functional CFTR (CFTR+) were compared to those without (CFTR-) to directly address the role of CFTR in inflammatory gene regulation. RESULTS: All lines maintained CFTR mRNA production and formation of tight junctions. CFTR+ lines displayed short circuit currents in response to forskolin, while the CFTR- lines did not. Baseline expression of cytokines IL6 and CXCL8 (IL8) was not different between the lines regardless of CFTR genotype. All lines responded to TNFα and IL1ß by increasing IL6 and CXCL8 mRNA levels, but the CFTR- lines produced more CXCL8 mRNA than the CFTR+ lines. Transcriptomes of 6 CFTR- and 6 CFTR+ lines, before and after stimulation by TNFα, were compared for differential expression as a function of CFTR genotype. While some genes appeared to be differentially expressed simply because of CFTR's absence, others required stimulation for differences to be apparent. CONCLUSION: Together, these data suggest cells respond to CFTR's absence by modulating transcriptional networks, some of which are only apparent when cells are exposed to different environmental contexts, such as inflammation. With regards to inflammation, these data suggest a model in which CFTR's absence leads to a poised, pro-inflammatory state of cells that is only revealed by stimulation.

Surface, Interface, and Temperature Effects on the Phase Separation and Nanoparticle Self Assembly of Bi-Metallic Ni0.5Ag0.5: A Molecular Dynamics Study.

Classical molecular dynamics (MD) simulations were used to investigate how free surfaces, as well as supporting substrates, affect phase separation in a NiAg alloy. Bulk samples, droplets, and droplets deposited on a graphene substrate were investigated at temperatures that spanned regions of interest in the bulk NiAg phase diagram, i.e., miscible and immiscible liquid, liquid-crystal, and crystal-crystal regions. Using MD simulations to cool down a bulk sample from 3000 K to 800 K, it was found that phase separation below 2400 K takes place in agreement with the phase diagram. When free surface effects were introduced, phase separation was accompanied by a core-shell transformation: spherical droplets created from the bulk samples became core-shell nanoparticles with a shell made mostly of Ag atoms and a core made of Ni atoms. When such droplets were deposited on a graphene substrate, the phase separation was accompanied by Ni layering at the graphene interface and Ag at the vacuum interface. Thus, it should be possible to create NiAg core-shell and layer-like nanostructures by quenching liquid NiAg samples on tailored substrates. Furthermore, interesting bimetallic nanoparticle morphologies might be tuned via control of the surface and interface energies and chemical instabilities of the system.

Surgical approach and the impact of epidural analgesia on survival after esophagectomy for cancer: A population-based retrospective cohort study.

BACKGROUND: Esophagectomy for esophageal cancer carries high morbidity and mortality, particularly in older patients. Transthoracic esophagectomy allows formal lymphadenectomy, but leads to greater perioperative morbidity and pain than transhiatal esophagectomy. Epidural analgesia may attenuate the stress response and be less immunosuppressive than opioids, potentially affecting long-term outcomes. These potential benefits may be more pronounced for transthoracic esophagectomy due to its greater physiologic impact. We evaluated the impact of epidural analgesia on survival and recurrence after transthoracic versus transhiatal esophagectomy. METHODS: A retrospective cohort study was performed using the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database. Patients aged ≥66 years with locoregional esophageal cancer diagnosed 1994-2009 who underwent esophagectomy were identified, with follow-up through December 31, 2013. Epidural receipt and surgical approach were identified from Medicare claims. Survival analyses adjusting for hospital esophagectomy volume, surgical approach, and epidural use were performed. A subgroup analysis restricted to esophageal adenocarcinoma patients was performed. RESULTS: Among 1,921 patients, 38% underwent transhiatal esophagectomy (n = 730) and 62% underwent transthoracic esophagectomy (n = 1,191). 61% (n = 1,169) received epidurals and 39% (n = 752) did not. Epidural analgesia was associated with transthoracic approach and higher volume hospitals. Patients with epidural analgesia had better 90-day survival. Five-year survival was higher with transhiatal esophagectomy (37.2%) than transthoracic esophagectomy (31.0%, p = 0.006). Among transthoracic esophagectomy patients, epidural analgesia was associated with improved 5-year survival (33.5% epidural versus 26.5% non-epidural, p = 0.012; hazard ratio 0.81, 95% confidence interval [0.70, 0.93]). Among the subgroup of esophageal adenocarcinoma patients undergoing transthoracic esophagectomy, epidural analgesia remained associated with improved 5-year survival (hazard ratio 0.81, 95% confidence interval [0.67, 0.96]); this survival benefit persisted in sensitivity analyses adjusting for propensity to receive an epidural. CONCLUSION: Among patients undergoing transthoracic esophagectomy, including a subgroup restricted to esophageal adenocarcinoma, epidural analgesia was associated with improved survival even after adjusting for other factors.

Epidural compared with non-epidural analgesia and cardiopulmonary complications after colectomy: A retrospective cohort study of 20,880 patients using a national quality database.

STUDY OBJECTIVE: Epidural analgesia may be associated with fewer postoperative complications and is associated with improved survival after colon cancer resection. This study used the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) to assess any association between epidural analgesia (versus non-epidural) and complications after colectomy. DESIGN: Retrospective cohort study. SETTING: 603 hospitals in the United States reporting data to NSQIP. PATIENTS: From 2014-15 data, 4176 patients undergoing colectomy with records indicating epidural analgesia were matched 1:4 via propensity scores to 16,704 patients without. INTERVENTIONS: None (observational study). MEASUREMENTS: Primarily, we assessed the association between epidural analgesia and a composite of cardiopulmonary complications using an average relative effect generalized estimating equations model. Secondary outcomes included neurologic, renal, and surgical complications and length of hospitalization. Sensitivity analyses repeated the analyses on a subgroup of only open colectomies. MAIN RESULTS: We found no association between epidural analgesia and the primary outcome: average relative effect (95% CI) 0.87 (0.68, 1.11); P = 0.25. We found no significant associations with any secondary outcomes. In the 8005 open colectomies, however, there was a significant association between epidural analgesia and fewer cardiopulmonary complications (average relative effect odds ratio [95% CI] of 0.58 [0.35, 0.95]; P = 0.03) and shortened hospital stay (HR for time to discharge [98.75% CI] of 1.10 [1.02, 1.18]; P < 0.001). CONCLUSIONS: We found no overall association between epidural analgesia and reduced complications after colectomy. In open colectomies, however, epidural analgesia was associated with fewer cardiopulmonary complications and shorter hospitalization. This may inform analgesic choice when planning open colectomy.

A nonrandomized trial of vitamin D supplementation for Barrett's esophagus.

BACKGROUND: Vitamin D deficiency may increase esophageal cancer risk. Vitamin D affects genes regulating proliferation, apoptosis, and differentiation and induces the tumor suppressor 15-hydroxyprostaglandin dehydrogenase (PGDH) in other cancers. This nonrandomized interventional study assessed effects of vitamin D supplementation in Barrett's esophagus (BE). We hypothesized that vitamin D supplementation may have beneficial effects on gene expression including 15-PGDH in BE. METHODS: BE subjects with low grade or no dysplasia received vitamin D3 (cholecalciferol) 50,000 international units weekly plus a proton pump inhibitor for 12 weeks. Esophageal biopsies from normal plus metaplastic BE epithelium and blood samples were obtained before and after vitamin D supplementation. Serum 25-hydroxyvitamin D was measured to characterize vitamin D status. Esophageal gene expression was assessed using microarrays. RESULTS: 18 study subjects were evaluated. The baseline mean serum 25-hydroxyvitamin D level was 27 ng/mL (normal ≥30 ng/mL). After vitamin D supplementation, 25-hydroxyvitamin D levels rose significantly (median increase of 31.6 ng/mL, p<0.001). There were no significant changes in gene expression from esophageal squamous or Barrett's epithelium including 15-PGDH after supplementation. CONCLUSION: BE subjects were vitamin D insufficient. Despite improved vitamin D status with supplementation, no significant alterations in gene expression profiles were noted. If vitamin D supplementation benefits BE, a longer duration or higher dose of supplementation may be needed.

New era of colorectal cancer screening.

Colorectal cancer (CRC) is the 2(nd) most common cancer in women and 3(rd) most common cancer in men worldwide. Most CRCs develop from adenomatous polyps arising from glandular epithelium. Tumor growth is initiated by mutation of the tumor suppressor gene APC and involves other genetic mutations in a stepwise process over years. Both hereditary and environmental factors contribute to the development of CRC. Screening has been proven to reduce the incidence of CRC. Screening has also contributed to the decrease in CRC mortality in the United States. However, CRC incidence and/or mortality remain on the rise in some parts of the world (Eastern Europe, Asia, and South America), likely due to factors including westernized diet, lifestyle, and lack of healthcare infrastructure. Multiple screening options are available, ranging from direct radiologic or endoscopic visualization tests that primarily detect premalignant or malignant lesions such as flexible sigmoidoscopy, optical colonoscopy, colon capsule endoscopy, computed tomographic colonography, and double contrast barium enema - to stool based tests which primarily detect cancers, including fecal DNA, fecal immunochemical test, and fecal occult blood test. The availability of some of these tests is limited to areas with high economic resources. This article will discuss CRC epidemiology, pathogenesis, risk factors, and screening modalities with a particular focus on new technologies.

Outcomes after endoscopic versus surgical therapy for early esophageal cancers in an older population.

BACKGROUND AND AIMS: Endoscopic treatment of early esophageal cancer provides an alternative to esophagectomy, which older patients may not tolerate. Population-based data regarding short-term outcomes and recurrence after endoscopic treatment for esophageal cancer are limited. We compared short-term outcomes, treated recurrence, and survival after endoscopic versus surgical therapy for early esophageal cancers in an older population. METHODS: We conducted a retrospective cohort study identifying patients aged ≥66 years with Tis or T1a tumors without nodal involvement diagnosed from 1994 to 2011 from the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. RESULTS: Of 2193 patients, 41% (n = 893) underwent esophagectomy, and 12% (n = 255) underwent endoscopic treatment within 6 months of diagnosis. Those treated endoscopically were older and more likely to have a Charlson comorbidity score ≥2. A composite endpoint, hospitalization and/or adverse events at 60 days, was higher in surgical patients than in the endoscopic treatment group (30% vs 12%; P < .001). In a Cox model stratified by histology, adjusting for other factors, endoscopic treatment was associated with improved 2-year survival (hazard ratio 0.51; 95% CI, 0.36-0.73). CONCLUSIONS: In this older population, a composite short-term endpoint was worse in the surgical group. Endoscopic treatment was associated with improved survival through 2 years. These results suggest that endoscopic treatment is a reasonable approach for early esophageal cancers in the elderly.

Serum 25-Hydroxyvitamin D Levels and the Risk of Dysplasia and Esophageal Adenocarcinoma in Patients with Barrett's Esophagus.

BACKGROUND: To date, there are no studies reporting an association between vitamin D and Barrett's esophagus (BE), the precursor for esophageal adenocarcinoma (EAC). AIMS: Our aim was to study the association between serum 25-hydroxyvitamin D (25(OH)D) levels and prevalence and incidence of dysplasia/EAC in BE. METHODS: Patients from our BE Registry cohort seen between 2000 and 2012 who had serum 25(OH)D levels measured were included. Age, gender, race, BE length, hiatal hernia size, and histological findings were recorded. Patients without high-grade dysplasia (HGD)/EAC at or within 1 year of index biopsy and who had follow-up endoscopies and 25(OH)D levels were studied for incidence of dysplasia/EAC. RESULTS: Among 429 patients with BE, the mean 25(OH)D level was 72 ± 31.2 nmol/L. Hundred and one (23.6 %) patients had deficiency (<50 nmol/L), 149 (34.7 %) had insufficiency (50-74.9 nmol/L), and 179 (41.7 %) had normal levels of 25(OH)D. There was no association between serum 25(OH)D levels and dysplasia (p = 0.90). In the incidence cohort of 246 patients with median follow-up of 46 months, there were 34 cases of low-grade dysplasia, 12 of HGD, and 5 of EAC. Change in 25(OH)D levels did not impact progression to dysplasia/EAC (every 5 nmol/L increase from baseline, hazard ratio 0.98; p = 0.62). CONCLUSIONS: Serum 25(OH)D levels were low in 58.3 % of our BE cohort. There was no association between 25(OH)D levels and prevalence or incidence of HGD/EAC in patients with BE. Further long-term studies are needed to study the association between vitamin D status and progression of dysplasia in BE.

New Archaeological Evidence for an Early Human Presence at Monte Verde, Chile.

Questions surrounding the chronology, place, and character of the initial human colonization of the Americas are a long-standing focus of debate. Interdisciplinary debate continues over the timing of entry, the rapidity and direction of dispersion, the variety of human responses to diverse habitats, the criteria for evaluating the validity of early sites, and the differences and similarities between colonization in North and South America. Despite recent advances in our understanding of these issues, archaeology still faces challenges in defining interdisciplinary research problems, assessing the reliability of the data, and applying new interpretative models. As the debates and challenges continue, new studies take place and previous research reexamined. Here we discuss recent exploratory excavation at and interdisciplinary data from the Monte Verde area in Chile to further our understanding of the first peopling of the Americas. New evidence of stone artifacts, faunal remains, and burned areas suggests discrete horizons of ephemeral human activity in a sandur plain setting radiocarbon and luminescence dated between at least ~18,500 and 14,500 cal BP. Based on multiple lines of evidence, including sedimentary proxies and artifact analysis, we present the probable anthropogenic origins and wider implications of this evidence. In a non-glacial cold climate environment of the south-central Andes, which is challenging for human occupation and for the preservation of hunter-gatherer sites, these horizons provide insight into an earlier context of late Pleistocene human behavior in northern Patagonia.

A comparison of the effects of epidural analgesia versus traditional pain management on outcomes after gastric cancer resection: a population-based study.

BACKGROUND AND OBJECTIVES: Epidural analgesia may increase survival after cancer surgery by reducing recurrence. This population-based study compared survival and treated recurrence after gastric cancer resection between patients receiving epidurals and those who did not. METHODS: We used the linked federal Surveillance, Epidemiology, and End Results Program/Medicare database to identify patients aged 66 years or older with nonmetastatic gastric carcinoma diagnosed 1996 to 2005 who underwent resection. Exclusions included diagnosis at autopsy, no Medicare Part B, familial cancer syndrome, emergency surgery, and laparoscopic procedures. Epidurals were identified by Current Procedural Terminology codes. Treated recurrence was defined as chemotherapy greater than or equal to 16 months and/or radiation greater than or equal to 12 months after surgery. Recurrence was compared by conditional logistic regression. Survival was compared via marginal Cox proportional hazards regression model. RESULTS: We identified 2745 patients, 766 of whom had epidural codes. Patients receiving epidurals were more likely to have regional disease, be white, and live in areas with relatively high socioeconomic status. Overall treated recurrence was 25.6% (27.5% epidural and 24.9% nonepidural). In the adjusted logistic regression, there was no difference in recurrence (odds ratio, 1.40; 95% confidence interval [CI], 0.96-2.05). Median survival did not differ: 28.1 months (95% CI, 24.8-32.3) in the epidural versus 27.4 months (95% CI, 24.8-30.0) in the nonepidural groups. The marginal Cox models showed no association between epidural use and mortality (adjusted hazard ratio, 0.93; 95% CI, 0.84-1.03). CONCLUSIONS: There was no difference between groups regarding treated recurrence or survival. Whether this is true or simply a result of insufficient power is unclear. Prospective studies are needed to provide stronger evidence.

Barrett's esophagus and the risk of obstructive sleep apnea: a case-control study.

BACKGROUND: Prior studies suggest that obstructive sleep apnea may be associated with gastroesophageal reflux disease, a strong risk factor for Barrett's esophagus. The goals of this pilot case-control study were to determine whether Barrett's esophagus patients have an increased likelihood of obstructive sleep apnea and to determine whether nocturnal gastroesophageal reflux symptoms affect the relationship between Barrett's esophagus and obstructive sleep apnea risk. METHODS: Patients with Barrett's esophagus completed the Berlin Questionnaire, a validated survey instrument identifying subjects at high risk for obstructive sleep apnea. Two outpatient control groups were recruited: 1) EGD Group, subjects matched to Barrett's esophagus cases by age, race, and gender with esophagogastroduodenoscopy negative for Barrett's esophagus; and 2) Colonoscopy Group, patients getting colonoscopy. Rates of scoring at high risk for obstructive sleep apnea were compared. Respondents were also questioned regarding severity of their typical gastroesophageal reflux symptoms and presence of nocturnal gastroesophageal reflux symptoms. RESULTS: The study included 287 patients (54 Barrett's esophagus, 62 EGD, and 171 colonoscopy subjects). Barrett's esophagus patients were slightly older than colonoscopy patients and more obese. 56% (n = 30) of Barrett's esophagus subjects scored at high risk for obstructive sleep apnea, compared with 42% (n = 26) of EGD subjects (OR 1.73, 95% CI [0.83, 3.62]) and 37% (n = 64) of colonoscopy patients (OR 2.08, 95% CI [1.12, 3.88]). The association between Barrett's esophagus and scoring at high risk for obstructive sleep apnea compared with colonoscopy patients disappeared after adjusting for age. Barrett's esophagus patients reported more severe typical heartburn and regurgitation symptoms than either control group. Among all subjects, patients with nocturnal reflux symptoms were more likely to score at high risk for obstructive sleep apnea than patients without nocturnal reflux. CONCLUSIONS: In this pilot study, a high proportion of Barrett's esophagus subjects scored at high risk for obstructive sleep apnea. Having Barrett's esophagus was associated with more severe gastroesophageal reflux symptoms, and nocturnal reflux symptoms were associated with scoring at high risk for obstructive sleep apnea. The need for obstructive sleep apnea screening in Barrett's esophagus patients with nocturnal gastroesophageal reflux symptoms should be further evaluated.