Predicting severe disease in patients diagnosed with seasonal influenza in the emergency department.

Objectives: We sought to develop an evidence-based tool to risk stratify patients diagnosed with seasonal influenza in the emergency department (ED). Methods: We performed a single-center retrospective cohort study of all adult patients diagnosed with influenza in a large tertiary care ED between 2008 and 2018. We evaluated demographics, triage vital signs, chest x-ray and laboratory results obtained in the ED. We used univariate and multivariate statistics to examine the composite primary outcome of death or need for intubation. We validated our findings in patients diagnosed between 2018 and 2020. Results: We collected data from 3128 subjects; 2196 in the derivation cohort and 932 in the validation cohort. Medical comorbidities, multifocal opacities or pleural effusion on chest radiography, older age, elevated respiratory rate, hypoxia, elevated blood urea nitrogen, blood glucose, blood lactate, and red blood cell distribution width were factors associated with intubation or death. We developed the Predicting Intubation in seasonal Influenza Patients diagnosed in the ED (PIIPED) risk-stratification tool from these factors. The PIIPED tool predicted intubation or death with an area under the receiver operating characteristic curve (AUC) of 0.899 in the derivation cohort and 0.895 in the validation cohort. A version of the tool including only factors available at ED triage, before laboratory or radiographic evaluation, exhibited AUC of 0.852 in the derivation cohort and 0.823 in the validation cohort. Conclusion: Clinical findings during an ED visit predict severe outcomes in patients with seasonal influenza. The PIIPED risk stratification tool shows promise but requires prospective validation.

Mitochondrial Trafficking of MLKL, Bak/Bax, and Drp1 Is Mediated by RIP1 and ROS which Leads to Decreased Mitochondrial Membrane Integrity during the Hyperglycemic Shift to Necroptosis.

Apoptosis and necroptosis overlap in their initial signaling but diverge to produce non-inflammatory and pro-inflammatory outcomes, respectively. High glucose pushes signaling in favor of necroptosis producing a hyperglycemic shift from apoptosis to necroptosis. This shift depends on receptor-interacting protein 1 (RIP1) and mitochondrial reactive oxygen species (ROS). Here, we show that RIP1, mixed lineage kinase domain-like (MLKL) protein, Bcl-2 agonist/killer (Bak), Bcl-2 associated x (Bax) protein, and dynamin-related protein 1 (Drp1) traffic to the mitochondria in high glucose. RIP1 and MLKL appear in the mitochondria in their activated, phosphorylated states while Drp1 appears in its activated, dephosphorylated state in high glucose. Mitochondrial trafficking is prevented in rip1 KO cells and upon treatment with N-acetylcysteine. Induction of ROS replicated the mitochondrial trafficking seen in high glucose. MLKL forms high MW oligomers in the outer and inner mitochondrial membranes while Bak and Bax form high MW oligomers in the outer mitochondrial membrane in high glucose, suggesting pore formation. MLKL, Bax, and Drp1 promoted cytochrome c release from the mitochondria as well as a decrease in mitochondrial membrane potential in high glucose. These results indicate that mitochondrial trafficking of RIP1, MLKL, Bak, Bax, and Drp1 are key events in the hyperglycemic shift from apoptosis to necroptosis. This is also the first report to show oligomerization of MLKL in the inner and outer mitochondrial membranes and dependence of mitochondrial permeability on MLKL.

Spontaneous intestinal perforation (SIP) will soon become the most common form of surgical bowel disease in the extremely low birth weight (ELBW) infant.

Recent data have revealed declines in the prevalence rates of NEC over the last decade in premature infants. In contrast, SIP has either remained steady or risen during the same epoch. These trends are consistent with our knowledge of the clinical arena. The ability to discern SIP contamination within NEC datasets has slowly improved. Additionally, quality improvement efforts are being utilized to reduce NEC through stewardship of antibiotics, acid inhibitors, central lines and blood products, as well as optimization of human milk diets. These forces are moving us to a new era, where NEC will no longer be the dominant surgical intestinal disease of the extremely preterm neonate. Indeed, in the extremely low birth weight (ELBW) population, SIP may already be the most prevalent reason for abdominal surgery. In this perspective, the reader will find supporting data and references for these assertions as well as predictions for the future.

Accuracy of after-hours trauma cervical spine CT reporting by radiology trainees: Experiences from two Australian teaching hospitals.

INTRODUCTION: Like many teaching hospitals in Australia, after-hours computed tomography (CT) reporting at our institution is undertaken by the on-call radiology registrar. The accuracy of these reports is important as management is often initiated based on the interim findings, prior to review by the consultant radiologist. A common exception to this approach is cervical CT (CCT), as many hospital protocols recommend patients to remain in spinal precautions until the report is finalised by a consultant, although there are very few studies to support this practice. METHODS: The interim registrar reports for all CCTs performed after-hours over a 12-month period were retrospectively reviewed. The final consultant report was used as the gold standard to establish accuracy of the registrar report. The primary outcome was discrepancy between the provisional and final reports. Any discrepancy was classified as either an 'overcall' or 'miss'. Discrepancies were graded by the RADPEER scoring system. RESULTS: A total of 1084 after-hours CCT studies were reviewed. The number of cases positive for injury was 37 (3.4%). The total number of discrepancies was 14 (discrepancy rate 1.3%), including 4 overcalls (0.3%) and 10 misses (0.9%). The discrepancy rates for junior and senior registrars were 1.7% and 0.7% respectively. Only 5 misses (0.5%) were considered clinically significant. CONCLUSION: Registrars reporting after-hours CCT have low rates of discrepancy with very few clinically significant misses. However, the reduced registrar sensitivity for detection of cervical injury highlights the ongoing importance of consultant review in the process of cervical spine clearance pathways.

Study protocol P-MAPS: microbiome as predictor of severity in acute pancreatitis-a prospective multicentre translational study.

BACKGROUND: Acute pancreatitis (AP) is an inflammatory disorder that causes a considerable economic health burden. While the overall mortality is low, around 20% of patients have a complicated course of disease resulting in increased morbidity and mortality. There is an emerging body of evidence that the microbiome exerts a crucial impact on the pathophysiology and course of AP. For several decades multiple clinical and laboratory parameters have been evaluated, and complex scoring systems were developed to predict the clinical course of AP upon admission. However, the majority of scoring systems are determined after several days and achieve a sensitivity around 70% for early prediction of severe AP. Thus, continued efforts are required to investigate reliable biomarkers for the early prediction of severity in order to guide early clinical management of AP patients. METHODS: We designed a multi-center, prospective clinical-translational study to test whether the orointestinal microbiome may serve as novel early predictor of the course, severity and outcome of patients with AP. We will recruit 400 AP patients and obtain buccal and rectal swabs within 72 h of admission to the hospital. Following DNA extraction, microbiome analysis will be performed using 3rd generation sequencing Oxford Nanopore Technologies (ONT) for 16S rRNA and metagenomic sequencing. Alpha- and beta-diversity will be determined and correlated to the revised Atlanta classification and additional clinical outcome parameters such as the length of hospital stay, number and type of complications, number of interventions and 30-day mortality. DISCUSSION: If AP patients show a distinct orointestinal microbiome dependent on the severity and course of the disease, microbiome sequencing could rapidly be implemented in the early clinical management of AP patients in the future. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04777812.

Shared-Task Worklists Improve Clinical Trial Recruitment Workflow in an Academic Emergency Department.

BACKGROUND: Clinical trials performed in our emergency department at Barnes-Jewish Hospital utilize a centralized infrastructure for alerting, screening, and enrollment with rule-based alerts sent to clinical research coordinators. Previously, all alerts were delivered as text messages via dedicated cellular phones. As the number of ongoing clinical trials increased, the volume of alerts grew to an unmanageable level. Therefore, we have changed our primary notification delivery method to study-specific, shared-task worklists integrated with our pre-existing web-based screening documentation system. OBJECTIVE: To evaluate the effects on screening and recruitment workflow of replacing text-message delivery of clinical trial alerts with study-specific shared-task worklists in a high-volume academic emergency department supporting multiple concurrent clinical trials. METHODS: We analyzed retrospective data on alerting, screening, and enrollment for 10 active clinical trials pre- and postimplementation of shared-task worklists. RESULTS: Notifications signaling the presence of potentially eligible subjects for clinical trials were more likely to result in a screen (p < 0.001) with the implementation of shared-task worklists compared with notifications delivered as text messages for 8/10 clinical trials. The change in workflow did not alter the likelihood of a notification resulting in an enrollment (p = 0.473). The Director of Research reported a substantial reduction in the amount of time spent redirecting clinical research coordinator screening activities. CONCLUSION: Shared-task worklists, with the functionalities we have described, offer a viable alternative to delivery of clinical trial alerts via text message directly to clinical research coordinators recruiting for multiple concurrent clinical trials in a high-volume academic emergency department.

Spectrally sparse optical coherence tomography.

Swept-source optical coherence tomography (OCT) typically relies on expensive and complex swept-source lasers, the cost of which currently limits the suitability of OCT for new applications. In this work, we demonstrate spectrally sparse OCT utilizing randomly spaced low-bandwidth optical chirps, suitable for low-cost implementation with telecommunications grade devices. Micron scale distance estimation accuracy with a resolution of 40 µm at a standoff imaging distance greater than 10 cm is demonstrated using a stepped chirp approach with approximately 23% occupancy of 4 THz bandwidth. For imaging of sparse scenes, comparable performance to full bandwidth occupancy is verified for metallic targets.

Prognostic factors associated with a restricted mouth opening (trismus) in patients with head and neck cancer: Systematic review.

BACKGROUND: To prescribe early trismus therapy, prognostic factors influencing the restricted mouth opening should be identified first. Our aim is to present an overview of these factors in patients with head and neck cancer. METHODS: PubMed, Cochrane, EMBASE, and CINAHL were searched using terms related to head and neck cancer and mouth opening. Risk of bias was assessed using the "Quality in Prognosis Studies" tool. A best evidence synthesis was performed. RESULTS: Of the identified 1418 studies, 53 were included. Three studies contained a prognostic multivariate model for a restricted mouth opening. CONCLUSIONS: Patients with head and neck cancer will most likely develop a restricted mouth opening when they have a large tumor near the masticatory muscles that requires extensive cancer treatment. A restricted mouth opening most likely occurs within 6 months after cancer treatment. Further research is necessary on factors related to healing tendency or pain intensity.

TRPV4 Antagonism Prevents Mechanically Induced Myotonia.

OBJECTIVE: Myotonia is caused by involuntary firing of skeletal muscle action potentials and causes debilitating stiffness. Current treatments are insufficiently efficacious and associated with side effects. Myotonia can be triggered by voluntary movement (electrically induced myotonia) or percussion (mechanically induced myotonia). Whether distinct molecular mechanisms underlie these triggers is unknown. Our goal was to identify ion channels involved in mechanically induced myotonia and to evaluate block of the channels involved as a novel approach to therapy. METHODS: We developed a novel system to enable study of mechanically induced myotonia using both genetic and pharmacologic mouse models of myotonia congenita. We extended ex vivo studies of excitability to in vivo studies of muscle stiffness. RESULTS: As previous work suggests activation of transient receptor potential vanilloid 4 (TRPV4) channels by mechanical stimuli in muscle, we examined the role of this cation channel. Mechanically induced myotonia was markedly suppressed in TRPV4-null muscles and in muscles treated with TRPV4 small molecule antagonists. The suppression of mechanically induced myotonia occurred without altering intrinsic muscle excitability, such that myotonia triggered by firing of action potentials (electrically induced myotonia) was unaffected. When injected intraperitoneally, TRPV4 antagonists lessened the severity of myotonia in vivo by approximately 80%. INTERPRETATION: These data demonstrate that there are distinct molecular mechanisms triggering electrically induced and mechanically induced myotonia. Our data indicates that activation of TRPV4 during muscle contraction plays an important role in triggering myotonia in vivo. Elimination of mechanically induced myotonia by TRPV4 inhibition offers a new approach to treating myotonia. ANN NEUROL 2020;88:297-308.

Improving Lung Function in Severe Heterogenous Emphysema with the Spiration Valve System (EMPROVE). A Multicenter, Open-Label Randomized Controlled Clinical Trial.

Rationale: Less invasive, nonsurgical approaches are needed to treat severe emphysema.Objectives: To evaluate the effectiveness and safety of the Spiration Valve System (SVS) versus optimal medical management.Methods: In this multicenter, open-label, randomized, controlled trial, subjects aged 40 years or older with severe, heterogeneous emphysema were randomized 2:1 to SVS with medical management (treatment) or medical management alone (control).Measurements and Main Results: The primary efficacy outcome was the difference in mean FEV1 from baseline to 6 months. Secondary effectiveness outcomes included: difference in FEV1 responder rates, target lobe volume reduction, hyperinflation, health status, dyspnea, and exercise capacity. The primary safety outcome was the incidence of composite thoracic serious adverse events. All analyses were conducted by determining the 95% Bayesian credible intervals (BCIs) for the difference between treatment and control arms. Between October 2013 and May 2017, 172 participants (53.5% male; mean age, 67.4 yr) were randomized to treatment (n = 113) or control (n = 59). Mean FEV1 showed statistically significant improvements between the treatment and control groups-between-group difference at 6 and 12 months, respectively, of 0.101 L (95% BCI, 0.060-0.141) and 0.099 L (95% BCI, 0.048-0.151). At 6 months, the treatment group had statistically significant improvements in all secondary endpoints except 6-minute-walk distance. Composite thoracic serious adverse event incidence through 6 months was greater in the treatment group (31.0% vs. 11.9%), primarily due to a 12.4% incidence of serious pneumothorax.Conclusions: In patients with severe heterogeneous emphysema, the SVS shows significant improvement in multiple efficacy outcomes, with an acceptable safety profile.Clinical trial registered with www.clinicaltrials.gov (NCT01812447).

Long term delay in onset of prevertebral hematoma following anterior cervical discectomy and fusion: A case report.

Post-operative hematoma following anterior cervical discectomy and fusion (ACDF) is an uncommon but feared complication. Typically, these complications present in the immediate post-operative period. We present a case of a 51 year-old woman who underwent a C4-5 ACDF for left sided radicular pain. Her immediate post-operative course was uncomplicated, but she presented 6 weeks subsequently to the emergency department with neck swelling, difficulty swallowing, cough, and shortness of breath. She was found to have a 4.5 cm anterior neck hematoma with settling of the instrumentation and a new C4 vertebral fragment protruding anteriorly. She underwent evacuation of hematoma without clear evidence of a bleeding source. After several days of observation, she was discharged home and ultimately had resolution of her presenting symptoms. Most hematomas resulting in airway compromise appear in the immediate post-operative period, but a high index of suspicion must remain high in any patient with a prior anterior cervical surgery presenting with symptoms of pre-vertebral compression or respiratory compromise.

Criterion for trismus in head and neck cancer patients: a verification study.

PURPOSE: Several cut-off points for trismus in head and neck cancer patients have been used. A mouth opening of 35 mm or less is most frequently used as cut-off point. Due to the variation in cut-off points, prevalence, risk factors and treatment outcomes of trismus cannot be studied in a uniform manner. To provide uniformity, we aimed to verify the cut-off point of 35 mm or less. Additionally, we aimed to determine associated covariates with reported difficulties when opening the mouth. METHODS: In a cross-sectional design, we measured the mouth opening in 671 head and neck cancer patients at the Department of Oral and Maxillofacial Surgery, at the University Medical Center Groningen. The cut-off point was determined using the receiver operating characteristic curve and Youden index, with reported difficulties when opening the mouth as criterion for trismus. Cut-off points for significant covariates were also determined. RESULTS: The Youden index was highest at 35 mm, with a sensitivity of 0.71 and a specificity of 0.86. Of the covariates analysed, type of treatment modality was significantly associated with reported difficulties when opening the mouth. The highest Youden index for patients treated with surgery alone was 37 mm and for patients treated with radiotherapy alone 33 mm. CONCLUSIONS: The cut-off point of 35 mm or less for trismus was confirmed in a head and neck cancer population and is recommended to be used in future studies. Patients receiving different treatment modalities experience difficulty when opening the mouth differently.

Trust After Just 45 Seconds? An Experimental Vignette Study of How Leader Behavior and Emotional States Influence Immediate Trust in Strangers.

Many critical and unexpected situations are handled by people that have never met. In the literature, development of immediate trust has been identified as a prerequisite for such temporary groups and leadership to function well. Limited experimental research has studied what leadership stimulates immediate trust between strangers. The present study investigate how four leadership styles, combining autocratic or democratic leadership behavior with low or high emotional stability, is related to immediate trust in a leader displayed through a 45-s video vignette of a car accident. A sample of 280 adults, randomly assigned to one of four conditions (1, autocratic/stable; 2, autocratic/unstable; 3, democratic/stable; 4, democratic/unstable) rated immediate trust after watching the vignette. The results show that autocratic and emotionally stable leaders were on average rated higher on immediate trust than all other leadership styles, after controlling for generalized trust.

Prevalence and prediction of trismus in patients with head and neck cancer: A cross-sectional study.

BACKGROUND: Trismus occurs frequently in patients with head and neck cancer. Determining the prevalence and associated factors of trismus would enable prediction of the risk of trismus for future patients. METHODS: Based on maximal mouth opening measurements, we determined the prevalence of trismus in 730 patients with head and neck cancer. Associated factors for trismus were analyzed using univariate analyses and multivariate logistic regression analyses. Based on the regression model, a calculation tool to predict trismus was made. RESULTS: Prevalence of trismus was 23.6%. Factors associated with trismus were: advanced age; partial or full dentition; tumors located at the maxilla; mandible; cheek; major salivary glands; oropharynx; an unknown primary; a free soft tissue transfer after surgery; reirradiation; and chemotherapy. CONCLUSION: About one-fourth of patients with head and neck cancer develop trismus. Based on prevalence and associated factors of trismus, a simple calculation tool predicts the risk of trismus in these patients.

Changing the paradigm of defining, detecting, and diagnosing NEC: Perspectives on Bell's stages and biomarkers for NEC.

Better means to diagnose and define necrotizing enterocolitis are needed to guide clinical practice and research. Adequacy of Bell's staging system for clinical practice and clarity of cases used in NEC clinical datasets has been a topic of controversy for some time. This article provides reasons why a better global definition for NEC is needed and offers a simple alternative bedside definition for preterm NEC called the "Two out of Three" rule. Some argue that biomarkers may fill knowledge gaps and provide greater precision in defining relevant features of a clinical disease like NEC. NEC biomarkers include markers of inflammation, intestinal dysfunction, hematologic changes, and clinical features. Development and reporting of NEC biomarkers should be guided by the FDA's BEST Consensus resource, "Biomarkers, EndpointS, & other Tools" and consistently report metrics so that studies can be compared and results pooled. Current practice in the NICU would be enhanced by clinical tools that effectively inform the clinical team that a baby is at increasing risk of NEC. Ideally, these tools will incorporate both clinical information about the baby as well as molecular signals that are indicative of NEC. While meaningful biomarkers for NEC and clinical tools exist, translation into practice is mediocre.

Use of Aspirin and P2Y12 Response Assays in Detecting Reversal of Platelet Inhibition With Platelet Transfusion in Patients With Traumatic Brain Injury on Antiplatelet Therapy.

BACKGROUND: At present, guidelines are lacking on platelet transfusion in patients with a traumatic intracranial bleed and history of antiplatelet therapy. The aspirin and P2Y 12 response unit (ARU and PRU, respectively) assays detect the effect of aspirin and P2Y 12 inhibitors in the cardiac population. OBJECTIVE: To describe the reversal of platelet inhibition after platelet transfusion using the ARU and PRU assays in patients with traumatic brain injury. METHODS: Between 2010 and 2015, we conducted a prospective comparative cohort study of patients presenting with a positive head computed tomography and a history of antiplatelet therapy. ARU and PRU assays were performed on admission and 6 hours after transfusion, with a primary end point of detection of disinhibition after platelet transfusion. RESULTS: One hundred seven patients were available for analysis. Seven percent of patients taking aspirin and 27% of patients taking clopidogrel were not therapeutic on admission per the ARU and PRU, respectively. After platelet transfusion, 51% of patients on any aspirin and 67% of patients on any clopidogrel failed to be reversed. ARU increased by 71 ± 76 per unit of apheresis platelets for patients taking any aspirin, and PRU increased by 48 ± 46 per unit of apheresis platelets for patients taking any clopidogrel. CONCLUSION: A significant percentage of patients taking aspirin or clopidogrel were not therapeutic and thus would be unlikely to benefit from a platelet transfusion. In patients with measured platelet inhibition, a single platelet transfusion was not sufficient to reverse platelet inhibition in almost half.

Utility of the Aspirin and P2Y12 Response Assays to Determine the Effect of Antiplatelet Agents on Platelet Reactivity in Traumatic Brain Injury.

BACKGROUND: Premorbid antithrombotic medication may worsen intracranial injury and outcome after traumatic brain injury (TBI). Routine laboratory tests are insufficient to evaluate platelet activity. OBJECTIVE: To profile the spectrum of platelet inhibition, as measured by aspirin and P2Y12 response unit assays, in a TBI population on antiplatelet therapy. METHODS: This single-center, prospective cohort study included patients presenting to our institution between November 2010 and January 2015 with a clinical history of TBI. Serum platelet reactivity levels were determined immediately on admission and analyzed using the aspirin and P2Y12 response unit assays; test results were reported as aspirin response units and P2Y12 response units. We report congruence between assay results and clinical history as well as differences in assay results between types of antiplatelet therapy. RESULTS: A sample of 317 patients was available for analysis, of which 87% had experienced mild TBI, 7% moderate, and 6% severe; the mean age was 71.5 years. The mean aspirin response units in patients with a history of any aspirin use was 456 ± 67 (range, 350-659), with 88% demonstrating therapeutic platelet inhibition. For clopidogrel, the mean P2Y12 response unit was 191 ± 70 (range, 51-351); 77% showed therapeutic response. CONCLUSION: Rapid measurement of antiplatelet function using the aspirin and P2Y12 response assays indicated as many as one fourth of patients on antiplatelet therapy do not have platelet dysfunction. Further research is required to develop guidelines for the use of these assays to guide platelet transfusion in the setting of TBI.

Risk stratification of Barrett's oesophagus using a non-endoscopic sampling method coupled with a biomarker panel: a cohort study.

BACKGROUND: Barrett's oesophagus predisposes to adenocarcinoma. However, most patients with Barrett's oesophagus will not progress and endoscopic surveillance is invasive, expensive, and fraught by issues of sampling bias and the subjective assessment of dysplasia. We investigated whether a non-endoscopic device, the Cytosponge, could be coupled with clinical and molecular biomarkers to identify a group of patients with low risk of progression suitable for non-endoscopic follow-up. METHODS: In this multicentre cohort study (BEST2), patients with Barrett's oesophagus underwent the Cytosponge test before their surveillance endoscopy. We collected clinical and demographic data and tested Cytosponge samples for a molecular biomarker panel including three protein biomarkers (P53, c-Myc, and Aurora kinase A), two methylation markers (MYOD1 and RUNX3), glandular atypia, and TP53 mutation status. We used a multivariable logistic regression model to compute the conditional probability of dysplasia status. We selected a simple model with high classification accuracy and applied it to an independent validation cohort. The BEST2 study is registered with ISRCTN, number 12730505. FINDINGS: The discovery cohort consisted of 468 patients with Barrett's oesophagus and intestinal metaplasia. Of these, 376 had no dysplasia and 22 had high-grade dysplasia or intramucosal adenocarcinoma. In the discovery cohort, a model with high classification accuracy consisted of glandular atypia, P53 abnormality, and Aurora kinase A positivity, and the interaction of age, waist-to-hip ratio, and length of the Barrett's oesophagus segment. 162 (35%) of 468 of patients fell into the low-risk category and the probability of being a true non-dysplastic patient was 100% (99% CI 96-100) and the probability of having high-grade dysplasia or intramucosal adenocarcinoma was 0% (0-4). 238 (51%) of participants were classified as of moderate risk; the probability of having high-grade dysplasia was 14% (9-21). 58 (12%) of participants were classified as high-risk; the probability of having non-dysplastic endoscopic biopsies was 13% (5-27), whereas the probability of having high-grade dysplasia or intramucosal adenocarcinoma was 87% (73-95). In the validation cohort (65 patients), 51 were non-dysplastic and 14 had high-grade dysplasia. In this cohort, 25 (38%) of 65 patients were classified as being low-risk, and the probability of being non-dysplastic was 96·0% (99% CI 73·80-99·99). The moderate-risk group comprised 27 non-dysplastic and eight high-grade dysplasia cases, whereas the high-risk group (8% of the cohort) had no non-dysplastic cases and five patients with high-grade dysplasia. INTERPRETATION: A combination of biomarker assays from a single Cytosponge sample can be used to determine a group of patients at low risk of progression, for whom endoscopy could be avoided. This strategy could help to avoid overdiagnosis and overtreatment in patients with Barrett's oesophagus. FUNDING: Cancer Research UK.