Disorders with Ophthalmic and Thoracic Involvement.

A variety of systemic conditions involve the thorax and the eyes. While subtle or nonspecific eye symptoms can be the initial clinical manifestation of some disorders, there can be additional manifestations in the thorax that lead to a specific diagnosis and affect patient outcomes. For instance, the initial clinical manifestation of Sjögren syndrome is dry eye or xerophthalmia; however, the presence of Sjögren lung disease represents a fourfold increase in mortality. Likewise, patients with acute sarcoidosis can initially present with pain and redness of the eye from uveitis in addition to fever and parotitis. Nearly 90% of patients with sarcoidosis have thoracic involvement, and the ophthalmologic symptoms can precede the thoracic symptoms by several years in some cases. Furthermore, a diagnosis made in one system can result in the screening of other organs as well as prompt genetic evaluation and examination of family members, such as in the setting of Marfan syndrome or Ehlers-Danlos syndrome. Multimodality imaging, particularly CT and MRI, plays a vital role in identification and characterization of these conditions. While it is helpful for ophthalmologists to be knowledgeable about these conditions and their associations so that they can order the pertinent radiologic studies, it is also important for radiologists to use the clues from ophthalmologic examination in addition to imaging findings to suggest a specific diagnosis. Systemic conditions with thoracic and ophthalmologic manifestations can be categorized as infectious, inflammatory, autoimmune, neoplastic, or hereditary in origin. The authors describe a spectrum of these conditions based on their underlying cause. ©RSNA, 2024.

Results of an International Survey on Spinal Imaging by the ASNR/ASSR/ESNR/ESSR "Nomenclature 3.0" Working Group.

Our goal was to determine if "Nomenclature 2.0," the classification of lumbar disk pathology consensus, should be updated. We conducted a social media and e-mail-based survey on preferences regarding the use of classification on magnetic resonance spine reporting. Members of the European Society of Neuroradiology, European Society of Musculoskeletal Radiology, American Society of Neuroradiology, and American Society of Spine Radiology received a 15-question online survey between February and March 2022. A total of 600 responses were received from 63 countries. The largest number of responses came from Italy and the United States. We found that 71.28% of respondents used Nomenclature 2.0, Classification of Lumbar Disk Pathology. But classification on stenosis is used less often: 53.94% and 60% of respondents do not use any classification of spinal canal stenosis and foraminal stenosis, respectively. When queried about which part of Nomenclature needs improving, most respondents asked for a Structured Reporting Template (SRT), even though 58.85% of respondents do not currently use any template and 54% routinely use a clinical information questionnaire. These results highlight the importance of an updated Nomenclature 3.0 version that integrates the classifications of lumbar disk disease and spinal canal and foraminal stenosis. Further attention should also be directed toward developing a robust endorsed SRT.

Comparative Outcomes of Cap Assisted Endoscopic Resection and Endoscopic Submucosal Dissection in Dysplastic Barrett's Esophagus.

BACKGROUND & AIMS: Endoscopic resection is an important component of the endoscopic treatment of Barrett's esophagus (BE) with dysplasia and intramucosal adenocarcinoma. Endoscopic resection can be performed by cap-assisted endoscopic mucosal resection (cEMR) or endoscopic submucosal dissection (ESD). We compared the histologic outcomes of ESD vs cEMR, followed by ablation. METHODS: We queried a prospectively maintained database of all patients undergoing cEMR and ESD followed by ablation at our institution from January 2006 to March 2020 and abstracted relevant demographic and clinical data. Our primary outcomes included the rate of complete remission of dysplasia (CRD): absence of dysplasia on surveillance histology, and complete remission of intestinal metaplasia (CRIM): absence of intestinal metaplasia. Our secondary outcome included complication rates. RESULTS: We included 537 patients in the study: 456 underwent cEMR and 81 underwent ESD. The cumulative probabilities of CRD at 2 years were 75.8% and 85.6% in the cEMR and ESD groups, respectively (P < .01). Independent predictors of CRD were as follows: ESD (hazard ratio [HR], 2.38; P < .01) and shorter BE segment length (HR, 1.11; P < .01). The cumulative probabilities of CRIM at 2 years were 59.3% and 50.6% in the cEMR and ESD groups, respectively (P > .05). The only independent predictor of CRIM was a shorter BE segment (HR, 1.16; P < .01). CONCLUSIONS: BE patients with dysplasia or intramucosal adenocarcinoma undergoing ESD reach CRD at higher rates than those treated with cEMR, although CRIM rates at 2 years and complication rates were similar between the 2 groups.

Best practices for building and curating databases for comparative analyses.

Comparative analyses have a long history of macro-ecological and -evolutionary approaches to understand structure, function, mechanism and constraint. As the pace of science accelerates, there is ever-increasing access to diverse types of data and open access databases that are enabling and inspiring new research. Whether conducting a species-level trait-based analysis or a formal meta-analysis of study effect sizes, comparative approaches share a common reliance on reliable, carefully curated databases. Unlike many scientific endeavors, building a database is a process that many researchers undertake infrequently and in which we are not formally trained. This Commentary provides an introduction to building databases for comparative analyses and highlights challenges and solutions that the authors of this Commentary have faced in their own experiences. We focus on four major tips: (1) carefully strategizing the literature search; (2) structuring databases for multiple use; (3) establishing version control within (and beyond) your study; and (4) the importance of making databases accessible. We highlight how one's approach to these tasks often depends on the goal of the study and the nature of the data. Finally, we assert that the curation of single-question databases has several disadvantages: it limits the possibility of using databases for multiple purposes and decreases efficiency due to independent researchers repeatedly sifting through large volumes of raw information. We argue that curating databases that are broader than one research question can provide a large return on investment, and that research fields could increase efficiency if community curation of databases was established.

Hippocampal recording via the RNS system reveals marked ipsilateral activation of epileptiform activity during Wada testing.

Wada testing remains an important component of pre-surgical testing to assess the feasibility of temporal lobectomy for patients with intractable epilepsy. In this procedure, an anesthetic is injected into either internal carotid artery while memory and language testing is performed, simulating the effect of temporal lobe resection. The mechanism remains poorly understood because the hippocampal vasculature is predominantly via the posterior circulation. We recorded hippocampal EEG during bilateral methohexital Wada testing in three patients who had previously been implanted with a responsive neurostimulation system (RNS) to determine the effect of the injections on hippocampal activity. In all six injections from three patients, methohexital caused immediate, transient increases in hippocampal spikes. With at least two of these injections, the electrographic changes were consistent with electrographic seizures. In all cases, the epileptiform activity was not apparent on scalp EEG and was without obvious clinical correlate other than the negative findings expected from the anesthetic. The results demonstrate the utility of intracranial EEG during Wada testing and suggest that the elicitation of seizures or continuous spiking might contribute to dysfunction of the hippocampus during the Wada test. We hypothesize that this effect is due to disconnection and disinhibition of medial temporal structures.

Neoplasia Detection Rate in Barrett's Esophagus and Its Impact on Missed Dysplasia: Results from a Large Population-Based Database.

BACKGROUND & AIMS: It is a challenge to detect dysplasia in Barrett's esophagus (BE) and esophageal adenocarcinomas (EACs) are missed in 25%-33% of cases. The neoplasia detection rate (NDR), defined as the rate of high-grade dysplasia (HGD) or EAC detection during initial surveillance endoscopy, has been proposed as a quality metric for endoscopic evaluation of patients with BE. However, current estimates are from referral center cohorts, which might overestimate NDR. Effects on rates of missed dysplasia are also unknown. We analyzed data from a large cohort of patients with BE to estimate the NDR and factors associated with it, and assess the effects of the NDR on the rate of missed dysplasia. METHODS: We analyzed data from 1066 patients in the Rochester Epidemiology Project-linked medical record system, a population-based cohort of patients with BE (confirmed by review of the endoscopic and histologic reports) from 11 southeastern Minnesota counties from 1991 through 2019. Biopsies reported to contain dysplasia were confirmed by expert gastrointestinal pathologists. The NDR was calculated as the rate of HGD or EAC detected by histologic analyses of biopsies collected during the first surveillance endoscopy. Patients without HGD or EAC at their initial endoscopy (n = 391) underwent repeat endoscopy within 12 months; HGD or EAC detected at the repeat endoscopy were considered to be missed on index endoscopy. Factors associated with NDR and missed dysplasia were identified using univariate and multivariate logistic regression models. RESULTS: The NDR was 4.9% (95% CI, 3.8-6.4); 3.1% of patients had HGD, 1.8% had EAC, and 10.6% had low-grade dysplasia. Factors associated with higher rates of detection of neoplasia included older age, male sex, smoking, increasing length of BE, and surveillance endoscopies by gastroenterologists. This NDR was associated with a substantially lower rate of missed dysplasia (13%). CONCLUSIONS: In an analysis of 1066 patients with BE in a population-based cohort, we found a lower NDR and lower rate of missed dysplasia than previously reported. NDR may have value as a quality metric in BE surveillance if validated in other cohorts.

Effects of Central Obesity on Esophageal Epithelial Barrier Function.

INTRODUCTION: We assessed if obesity perturbs the esophageal epithelial barrier function independent of promotion of gastroesophageal reflux (GER). METHODS: Thirty-eight participants were divided into 4 groups: Obesity-/GER-, Obesity+/GER-, Obesity-/GER+, and Obesity+/GER+. Esophageal intercellular space and desmosome density (structural integrity) and fluorescein leak (functional integrity) were measured. RESULTS: The Obesity+/GER- group demonstrated increased intercellular space, reduced desmosome density, and increased fluorescein leak compared with control subjects. These changes were similar but not additive to findings seen in Obesity-/GER + and Obesity+/GER+ patients. DISCUSSION: Central obesity impairs structural and functional integrity of the esophageal barrier independent of GER, likely predisposing to esophageal injury.

DECT in Detection of Vertebral Fracture-associated Bone Marrow Edema: A Systematic Review and Meta-Analysis with Emphasis on Technical and Imaging Interpretation Parameters.

Background Dual-energy CT (DECT) shows promising performance in detecting bone marrow edema (BME) associated with vertebral body fractures. However, the optimal technical and image interpretation parameters are not well described. Purpose To conduct a systematic review and meta-analysis to determine the diagnostic performance of DECT in detecting BME associated with vertebral fractures (VFs), using different technical and image interpretation parameters, compared with MRI as the reference standard. Materials and Methods A systematic literature search was performed on July 9, 2020, to identify studies evaluating DECT performance for in vivo detection of vertebral BME. A random-effects model was used to derive estimates of the diagnostic accuracy parameters of DECT. The impact of relevant covariates in technical, image interpretation, and study design parameters on the diagnostic performance of DECT was investigated using subgroup analyses. Results Seventeen studies (with 742 of 2468 vertebrae with BME at MRI) met inclusion criteria. Pooled estimates of sensitivity, specificity, and area under the curve of DECT for vertebral body BME were 89% (95% CI: 84%, 92%), 96% (95% CI: 92%, 98%), and 96% (95% CI: 94%, 97%), respectively. Single-source consecutive scanning showed poor specificity (78%) compared with the dual-source technique (98%, P < .001). Specificity was higher using bone and soft-tissue kernels (98%) compared with using only soft-tissue kernels (90%, P = .001). Qualitative assessment had a better specificity (97%) versus quantitative assessment (90%) of DECT images (P = .01). Experienced readers showed considerably higher specificity (96%) compared with trainees (79%, P = .01). DECT sensitivity improved using a higher difference between low- and high-energy spectra (90% vs 83%, P = .04). Conclusion Given its high specificity, the detection of vertebral bone marrow edema with dual-energy CT (DECT) associated with vertebral fracture may obviate confirmatory MRI in an emergency setting. Technical parameters, such as the dual-source technique, both bone and soft-tissue kernels, and qualitative assessment by experienced readers, can ensure the high specificity of DECT. © RSNA, 2021 Online supplemental material is available for this article.

Outcomes of radiofrequency ablation by manual versus self-sizing circumferential balloon catheters for the treatment of dysplastic Barrett's esophagus: a multicenter comparative cohort study.

BACKGROUND AND AIMS: Radiofrequency ablation (RFA) is the preferred ablative modality for treating dysplastic Barrett's esophagus. The recently introduced self-sizing circumferential ablation catheter eliminates the need for a sizing balloon. Although it enhances efficiency, outcomes have not been compared with the previous manual-sizing catheter. We evaluated the comparative safety and efficacy of these 2 ablation systems in a large, multicenter cohort. METHODS: Patients undergoing RFA at 3 tertiary care centers from 2005 to 2018 were included. Circumferential RFA was performed in a standard fashion, followed by focal RFA as needed. Outcomes were compared between the self-sizing and manual-sizing groups. The primary outcome was the rate of adverse events, including strictures, perforation, and bleeding. Secondary outcomes were procedure time and treatment efficacy, as assessed by rates and time to complete eradication of dysplasia (CE-D) and intestinal metaplasia (CE-IM). RESULTS: Three hundred eighteen patients were included, 90 (28.3%) treated with the self-sizing catheter and 228 (71.7%) with the manual-sizing catheter. Twenty-one patients (6.6%) developed strictures (8 [8.9%] in the self-sizing group and 13 [5.7%] in the manual-sizing group, P = .32). Of the self-sizing strictures, 75% occurred at the 12J dose before widespread adoption of the current 10J treatment standard. One patient developed bleeding, and no perforations were encountered. Procedure time was significantly shorter in the self-sizing group. No significant differences were observed in rates of and time to CE-D and CE-IM. CONCLUSIONS: These findings suggest that both systems are comparable in safety and efficacy. The use of the self-sizing system may enhance the efficiency of RFA for treating dysplastic Barrett's esophagus.

Development and Pilot Testing of Decision Aid for Shared Decision Making in Barrett's Esophagus With Low-Grade Dysplasia.

GOALS: To develop an encounter decision aid [Barrett's esophagus Choice (BE-Choice)] for patients and clinicians to engage in shared decision making (SDM) for management of BE with low-grade dysplasia (BE-LGD) and assess its impact on patient-important outcomes. BACKGROUND: Currently, there are 2 strategies for management of BE-LGD-endoscopic surveillance and ablation. SDM can help patients decide on their preferred management option. STUDY: Phase-I: Patients and clinicians were engaged in a user-centered design approach to develop BE-Choice. Phase-I included review of evidence on BE-LGD management, observation of usual care (UC), creation, field-testing, and iterative development of BE-Choice in clinical settings. Phase-II: Impact of BE-Choice on patient-important outcomes (patient knowledge, decisional conflict, and patient involvement in decision making) was assessed using a controlled before-after study design (UC vs. BE-Choice). RESULTS: Phase-I: Initial prototype was designed with observation of 8 clinical encounters. With field-testing, 3 successive iterations were made before finalizing BE-Choice. BE-Choice was paper based and fulfilled the qualifying criteria of International patient decision aid standards. Phase II: 29 patients were enrolled, 8 to UC and 21 to BE-Choice. Compared with UC, use of BE-Choice improved patient knowledge (90.4% vs. 70.5%; P=0.03), decisional comfort (89.6 vs. 71.9; P=0.01), and patient involvement (OPTION score: 27.1 vs. 19.2; P=0.01). CONCLUSIONS: BE-Choice is a feasible and effective decision aid to promote SDM in the management of BE-LGD. On pilot testing, BE-Choice had promising impact on patient-important outcomes. A larger multicenter trial is needed to confirm our results and promote widespread use of BE-Choice.

Effects of Collateral Status on Infarct Distribution Following Endovascular Therapy in Large Vessel Occlusion Stroke.

BACKGROUND AND PURPOSE: We aim to examine effects of collateral status and post-thrombectomy reperfusion on final infarct distribution and early functional outcome in patients with anterior circulation large vessel occlusion ischemic stroke. METHODS: Patients with large vessel occlusion who underwent endovascular intervention were included in this study. All patients had baseline computed tomography angiography and follow-up magnetic resonance imaging. Collateral status was graded according to the criteria proposed by Miteff et al and reperfusion was assessed using the modified Thrombolysis in Cerebral Infarction (mTICI) system. We applied a multivariate voxel-wise general linear model to correlate the distribution of final infarction with collateral status and degree of reperfusion. Early favorable outcome was defined as a discharge modified Rankin Scale score ≤2. RESULTS: Of the 283 patients included, 129 (46%) had good, 97 (34%) had moderate, and 57 (20%) had poor collateral status. Successful reperfusion (mTICI 2b/3) was achieved in 206 (73%) patients. Poor collateral status was associated with infarction of middle cerebral artery border zones, whereas worse reperfusion (mTICI scores 0-2a) was associated with infarction of middle cerebral artery territory deep white matter tracts and the posterior limb of the internal capsule. In multivariate regression models, both mTICI (P<0.001) and collateral status (P<0.001) were among independent predictors of final infarct volumes. However, mTICI (P<0.001), but not collateral status (P=0.058), predicted favorable outcome at discharge. CONCLUSIONS: In this cohort of patients with large vessel occlusion stroke, both the collateral status and endovascular reperfusion were strongly associated with middle cerebral artery territory final infarct volumes. Our findings suggesting that baseline collateral status predominantly affected middle cerebral artery border zones infarction, whereas higher mTICI preserved deep white matter and internal capsule from infarction; may explain why reperfusion success-but not collateral status-was among the independent predictors of favorable outcome at discharge. Infarction of the lentiform nuclei was observed regardless of collateral status or reperfusion success.

Fixed Compared With Autoregulation-Oriented Blood Pressure Thresholds After Mechanical Thrombectomy for Ischemic Stroke.

Background and Purpose- Loss of cerebral autoregulation in the acute phase of ischemic stroke leaves patients vulnerable to blood pressure (BP) changes. Effective BP management after endovascular thrombectomy may protect the brain from hypoperfusion or hyperperfusion. In this observational study, we compared personalized, autoregulation-based BP targets to static systolic BP thresholds. Methods- We prospectively enrolled 90 patients undergoing endovascular thrombectomy for stroke. Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy-derived tissue oxygenation (a cerebral blood flow surrogate) in response to changes in mean arterial pressure. The resulting autoregulatory index was used to trend the BP range at which autoregulation was most preserved. Percent time that mean arterial pressure exceeded the upper limit of autoregulation or decreased below the lower limit of autoregulation was calculated for each patient. Time above fixed systolic BP thresholds was computed in a similar fashion. Functional outcome was measured with the modified Rankin Scale at 90 days. Results- Personalized limits of autoregulation were successfully computed in all 90 patients (age 71.6±16.2, 47% female, mean National Institutes of Health Stroke Scale 13.9±5.7, monitoring time 28.0±18.4 hours). Percent time with mean arterial pressure above the upper limit of autoregulation associated with worse 90-day outcomes (odds ratio per 10% 1.84 [95% CI, 1.3-2.7] P=0.002), and patients with hemorrhagic transformation spent more time above the upper limit of autoregulation (10.9% versus 16.0%, P=0.042). Although there appeared to be a nonsignificant trend towards worse outcome with increasing time above systolic BP thresholds of 140 mm Hg and 160 mm Hg, the effect sizes were smaller compared with the personalized approach. Conclusions- Noninvasive determination of personalized BP thresholds for stroke patients is feasible. Deviation from these limits may increase risk of further brain injury and poor functional outcome. This approach may present a better strategy compared with the classical approach of maintaining systolic BP below a predetermined value, though a randomized trial is needed to determine the optimal approach for hemodynamic management.

Accurate Nonendoscopic Detection of Barrett's Esophagus by Methylated DNA Markers: A Multisite Case Control Study.

INTRODUCTION: Nonendoscopic Barrett's esophagus (BE) screening may help improve esophageal adenocarcinoma outcomes. We previously demonstrated promising accuracy of methylated DNA markers (MDMs) for the nonendoscopic diagnosis of BE using samples obtained from a capsule sponge-on-string (SOS) device. We aimed to assess the accuracy of these MDMs in an independent cohort using a commercial grade assay. METHODS: BE cases had ≥ 1 cm of circumferential BE with intestinal metaplasia; controls had no endoscopic evidence of BE. The SOS device was withdrawn 8 minutes after swallowing, followed by endoscopy (the criterion standard). Highest performing MDMs from a previous study were blindly assessed on extracted bisulfite-converted DNA by target enrichment long-probe quantitative amplified signal (TELQAS) assays. Optimal MDM combinations were selected and analyzed using random forest modeling with in silico cross-validation. RESULTS: Of 295 patients consented, 268 (91%) swallowed the SOS device; 112 cases and 89 controls met the pre-established inclusion criteria. The median BE length was 6 cm (interquartile range 4-9), and 50% had no dysplasia. The cross-validated sensitivity and specificity of a 5 MDM random forest model were 92% (95% confidence interval 85%-96%) and 94% (95% confidence interval 87%-98%), respectively. Model performance was not affected by age, gender, or smoking history but was influenced by the BE segment length. SOS administration was well tolerated (median [interquartile range] tolerability 2 [0, 4] on 10 scale grading), and 95% preferred SOS over endoscopy. DISCUSSION: Using a minimally invasive molecular approach, MDMs assayed from SOS samples show promise as a safe and accurate nonendoscopic test for BE prediction.

Outcomes of patients with submucosal (T1b) esophageal adenocarcinoma: a multicenter cohort study.

BACKGROUND AND AIMS: The treatment of submucosal (T1b) esophageal adenocarcinoma (EAC) remains in evolution, with some evidence supporting endoscopic management of low-risk lesions. Using a multicenter cohort, we evaluated outcomes of patients with T1b EAC and predictors of survival. METHODS: Patients diagnosed between 2001 and 2016 with T1b EAC were identified from 3 academic medical centers in the United States. Demographic, clinical, and outcome data were collected. Outcomes studied were overall and cancer-free survival. Cox proportional hazards models were constructed to assess independent predictors of survival. RESULTS: One hundred forty-one patients were included, of whom 68 (48%) underwent esophagectomy and 73 (52%) were treated endoscopically. Most patients (85.8%) had high-risk histologic features. Thirty-day operative mortality was 2.9%. Median follow-up in the esophagectomy and endoscopic cohorts was 49.4 and 43.4 months, respectively. Patients treated endoscopically were older with higher comorbidity scores, with 46 (63%) achieving histologic remission. Nineteen patients (26.0%) also received chemoradiation. Five-year overall survival rates in the surgical and endoscopic cohorts were 89% and 59%, respectively, whereas 5-year cancer-free survival rates were 92% and 69%. Presence of high-risk histologic features was associated with reduced overall survival. CONCLUSIONS: In this large multicenter study of patients with T1b EAC, esophagectomy was associated with improved overall but not cancer-free survival. High-risk histologic features were associated with poorer survival.

Effect of valine on myotube insulin sensitivity and metabolism with and without insulin resistance.

Population data have consistently demonstrated a correlation between circulating branched-chain amino acids (BCAA) and insulin resistance. Most recently valine catabolite, 3-hydroxyisobutyrate, has emerged as a potential cause of BCAA-mediated insulin resistance; however, it is unclear if valine independently promotes insulin resistance. It is also unclear if excess valine influences the ability of cells to degrade BCAA. Therefore, this study investigated the effect of valine on muscle insulin signaling and related metabolism in vitro. C2C12 myotubes were treated with varying concentrations (0.5 mM-2 mM) of valine for up to 48 h. qRT-PCR and western blot were used to measure metabolic gene and protein expression, respectively. Insulin sensitivity (indicated by pAkt:Akt), metabolic gene and protein expression, and cell metabolism were also measured following valine treatment both with and without varying levels of insulin resistance. Mitochondrial and glycolytic metabolism were measured via oxygen consumption and extracellular acidification rate, respectively. Valine did not alter regulators of mitochondrial biogenesis or glycolysis; however, valine reduced branched-chain alpha-keto acid dehydrogenase a (Bckdha) mRNA (but not protein) expression which was exacerbated by insulin resistance. Valine treatment had no effect on pAkt:Akt following either acute or 48-h treatment, regardless of insulin stimulation or varying levels of insulin resistance. In conclusion, despite consistent population data demonstrating a relationship between circulating BCAA (and related metabolites) and insulin resistance, valine does not appear to independently alter insulin sensitivity or worsen insulin resistance in the myotube model of skeletal muscle.

Timeline and location of recurrence following successful ablation in Barrett's oesophagus: an international multicentre study.

OBJECTIVE: Surveillance interval protocols after complete remission of intestinal metaplasia (CRIM) post radiofrequency ablation (RFA) in Barrett's oesophagus (BE) are currently empiric and not based on substantial evidence. We aimed to assess the timeline, location and patterns of recurrence following CRIM to inform these guidelines. DESIGN: Data on patients undergoing RFA for BE were obtained from prospectively maintained databases of five (three USA and two UK) tertiary referral centres. RFA was performed until CRIM was confirmed on two consecutive endoscopies. RESULTS: 594 patients achieved CRIM as of 1 May 2017. 151 subjects developed recurrent BE over a median (IQR) follow-up of 2.8 (1.4-4.4) years. There was 19% cumulative recurrence risk of any BE within 2 years and an additional 49% risk over the next 8.6 years. There was no evidence of a clinically meaningful change in the recurrence hazard rate of any BE, dysplastic BE or high-grade dysplasia/cancer over the duration of follow-up, with an estimated 2% (95% CI -7% to 12%) change in recurrence rate of any BE in a doubling of follow-up time. 74% of BE recurrences developed at the gastro-oesophageal junction (GOJ) (24.1% were dysplastic) and 26% in the tubular oesophagus. The yield of random biopsies from the tubular oesophagus, in the absence of visible lesions, was 1% (BE) and 0.2% (dysplasia). CONCLUSIONS: BE recurrence risk following CRIM remained constant over time, suggesting that lengthening of follow-up intervals, at least in the first 5 years after CRIM, may not be advisable. Sampling the GOJ is critical to detecting recurrence. The requirement for random biopsies of the neosquamous epithelium in the absence of visible lesions may need to be re-evaluated.

Macroevolutionary Patterning in Glucocorticoids Suggests Different Selective Pressures Shape Baseline and Stress-Induced Levels.

Glucocorticoid (GC) hormones are important phenotypic mediators across vertebrates, but their circulating concentrations can vary markedly. Here we investigate macroevolutionary patterning in GC levels across tetrapods by testing seven specific hypotheses about GC variation and evaluating whether the supported hypotheses reveal consistent patterns in GC evolution. If selection generally favors the "supportive" role of GCs in responding effectively to challenges, then baseline and/or stress-induced GCs may be higher in challenging contexts. Alternatively, if selection generally favors "protection" from GC-induced costs, GCs may be lower in environments where challenges are more common or severe. The predictors of baseline GCs were all consistent with supportive effects: levels were higher in smaller organisms and in those inhabiting more energetically demanding environments. During breeding, baseline GCs were also higher in populations and species with fewer lifetime opportunities to reproduce. The predictors of stress-induced GCs were instead more consistent with the protection hypothesis: during breeding, levels were lower in organisms with fewer lifetime reproductive opportunities. Overall, these patterns indicate a surprising degree of consistency in how some selective pressures shape GCs across broad taxonomic scales; at the same time, in challenging environments selection appears to operate on baseline and stress-induced GCs in distinct ways.

Acceptability, Accuracy, and Safety of Disposable Transnasal Capsule Endoscopy for Barrett's Esophagus Screening.

BACKGROUND & AIMS: Screening for Barrett's esophagus (BE) with conventional esophagogastroduodenoscopy (C-EGD) is expensive. We assessed the performance of a clinic-based, single use transnasal capsule endoscope (EG Scan II) for the detection of BE, compared to C-EGD as the reference standard. METHODS: We performed a prospective multicenter cohort study of patients with and without BE recruited from 3 referral centers (1 in the United States and 2 in the United Kingdom). Of 200 consenting participants, 178 (89%) completed both procedures (11% failed EG Scan due to the inability to intubate the nasopharynx). The mean age of participants was 57.9 years and 67% were male. The prevalence of BE was 53%. All subjects underwent the 2 procedures on the same day, performed by blinded endoscopists. Patients completed preference and validated tolerability (10-point visual analogue scale [VAS]) questionnaires within 14 days of the procedures. RESULTS: A higher proportion of patients preferred the EG Scan (54.2%) vs the C-EGD (16.7%) (P < .001) and the EG Scan had a higher VAS score (7.2) vs the C-EGD (6.4) (P = .0004). No serious adverse events occurred. The EG Scan identified any length BE with a sensitivity value of 0.90 (95% CI, 0.83-0.96) and a specificity value of 0.91 (95% CI, 0.82-0.96). The EG Scan identified long segment BE with a sensitivity value of 0.95 and short segment BE with a sensitivity values of 0.87. CONCLUSIONS: In a prospective study, we found the EG Scan to be safe and to detect BE with higher than 90% sensitivity and specificity. A higher proportion of patients preferred the EG Scan to C-EGD. This device might be used as a clinic-based tool to screen populations at risk for BE. ISRCTN registry identifier: 70595405; ClinicalTrials.gov no: NCT02066233.

Rapid evolution of testis size relative to sperm morphology suggests that post-copulatory selection targets sperm number in Anolis lizards.

Post-copulatory sexual selection is thought to be responsible for much of the extraordinary diversity in sperm morphology across metazoans. However, the extent to which post-copulatory selection targets sperm morphology versus sperm production is generally unknown. To address this issue, we simultaneously characterized the evolution of sperm morphology (length of the sperm head, midpiece and flagellum) and testis size (a proxy for sperm production) across 26 species of Anolis lizards, a group in which sperm competition is likely. We found that the length of the sperm midpiece has evolved 2-3 times faster than that of the sperm head or flagellum, suggesting that midpiece size may be the most important aspect of sperm morphology with respect to post-copulatory sexual selection. However, testis size has evolved faster than any aspect of sperm morphology or body size, supporting the hypothesis that post-copulatory sexual selection acts more strongly upon sperm production than upon sperm morphology. Likewise, evolutionary increases in testis size, which typically indicate increased sperm competition, are not associated with predictable changes in sperm morphology, suggesting that any effects of post-copulatory selection on sperm morphology are either weak or variable in direction across anoles. Collectively, our results suggest that sperm production is the primary target of post-copulatory sexual selection in this lineage.

Barrett Esophagus Length, Nodularity, and Low-grade Dysplasia are Predictive of Progression to Esophageal Adenocarcinoma.

GOALS: To investigate factors predictive of progression from nondysplastic Barrett esophagus (NDBE) or low-grade dysplasia (LGD) to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) using a large, prospective cohort of patients, wherein all esophageal biopsies undergo expert gastrointestinal pathologist review. BACKGROUND: Efficacy and cost-effectiveness of endoscopic surveillance to detect incident EAC in the setting of Barrett esophagus (BE), particularly in NDBE patients, is questioned. Previous studies have reported factors predictive of progression to EAC to guide surveillance intervals, but their strength is limited by small sample size and absence of expert gastrointestinal pathologist involvement in esophageal biopsy review. STUDY: NDBE and LGD subjects were identified from a prospective registry in a tertiary care center. "Progressors" were BE subjects who developed HGD/EAC>12 months after the initial NDBE or LGD diagnosis. Cox proportional hazards model were used to identify predictors of progression. RESULTS: In total, 318 with NDBE and 301 with BE-LGD (mean age, 62.6 y, 85% male) were included. The mean follow-up was 5.3 years. The 7 NDBE and 21 LGD subjects progressed to HGD/EAC. BE length [hazards ratio (HR), 1.16; 95% confidence interval (CI), 1.03-1.29], presence of nodularity (HR, 4.98; 95% CI, 1.80-11.7), and baseline LGD (HR, 2.57; 95% CI, 1.13-6.57) were significant predictors of progression on multivariate analysis. CONCLUSIONS: In this well-defined cohort of NDBE and BE-LGD subjects, BE length, presence of LGD, and nodularity were independent predictors of progression to HGD/EAC. These factors may aid in identifying high-risk patients who may benefit from closer endoscopic surveillance/therapy.