Adjunctive glucocorticoid therapy for Pneumocystis jirovecii pneumonia in solid organ transplant recipients: A multicenter cohort, 2015-2020.

Solid organ transplant recipients (SOTRs) frequently receive adjunctive glucocorticoid therapy (AGT) for Pneumocystis jirovecii pneumonia (PJP). This multicenter cohort of SOTRs with PJP admitted to 20 transplant centers in Canada, the United States, Europe, and Australia, was examined for whether AGT was associated with a lower rate of all-cause intensive care unit (ICU) admission, 90-day death, or a composite outcome (ICU admission or death). Of 172 SOTRs with PJP (median [IQR] age: 60 (51.5-67.0) years; 58 female [33.7%]), the ICU admission and death rates were 43.4%, and 20.8%, respectively. AGT was not associated with a reduced risk of ICU admission (adjusted odds ratio [aOR] [95% CI]: 0.49 [0.21-1.12]), death (aOR [95% CI]: 0.80 [0.30-2.17]), or the composite outcome (aOR [95% CI]: 0.97 [0.71-1.31]) in the propensity score-adjusted analysis. AGT was not significantly associated with at least 1 unit of the respiratory portion of the Sequential Organ Failure Assessment score improvement by day 5 (12/37 [32.4%] vs 39/111 [35.1%]; P = .78). We did not observe significant associations between AGT and ICU admission or death in SOTRs with PJP. Our findings should prompt a reevaluation of routine AGT administration in posttransplant PJP treatment and highlight the need for interventional studies.

Surveillance in Barrett's Esophagus: Challenges, Progress, and Possibilities.

Endoscopic surveillance of Barrett's esophagus, aiming to detect prevalent dysplasia and adenocarcinoma, followed by effective endoscopic treatment, is an integral part of the esophageal adenocarcinoma prevention paradigm. However, several limitations, such as the subtle appearance of dysplasia, sampling error (inherent in current surveillance protocols), and noncompliance with surveillance recommendations, lead to missed dysplasia and neoplasia, reducing the effectiveness of surveillance as currently practiced. Careful endoscopic assessment with high-resolution white-light endoscopy, dye-based or electronic chromoendoscopy, and comprehensive sampling of the BE mucosa, remains the cornerstone of endoscopic surveillance. Emerging innovations in this area span the gamut of more efficient sampling methods, advanced imaging tools, artificial intelligence, and molecular marker-powered approaches as adjuncts, to identify prevalent and predict incident dysplasia or adenocarcinoma. Development and implementation of validated quality indicators will allow additional advancement of this critical field. These approaches will hopefully enable efficient and effective cancer prevention and treatment.

Barrett's Esophagus Risk Factors in Patients Without Gastroesophageal Reflux: A Large Population-Based Study.

Esophageal adenocarcinoma (EAC) is a lethal malignancy with an abysmal 5-year survival rate of <20%.1 Barrett's esophagus (BE) is the only known precursor to EAC.1,2 BE is characterized by intestinal metaplasia of the distal esophagus, typically arising in the setting of gastroesophageal reflux disease (GERD).1 Hence, chronic GERD symptoms are an essential criterion for BE screening in most gastroenterology guidelines, alongside other BE risk factors including age >50 years, male sex, White race, history of tobacco smoking, hiatal hernia (HH) diagnosis, obesity, and family history of BE/EAC in first-degree relatives.1,3 Dysplastic BE and early stage EAC are amenable to endoscopic eradication therapy, highlighting the importance of BE/EAC screening and surveillance.4.

The Evolving Role of Artificial Intelligence in Gastrointestinal Histopathology: An Update.

Significant advances in artificial intelligence (AI) over the past decade potentially may lead to dramatic effects on clinical practice. Digitized histology represents an area ripe for AI implementation. We describe several current needs within the world of gastrointestinal histopathology, and outline, using currently studied models, how AI potentially can address them. We also highlight pitfalls as AI makes inroads into clinical practice.

Prevalence and Predictors of Barrett's Esophagus After Negative Initial Endoscopy: Analysis From Two National Databases.

BACKGROUND & AIMS: Guidelines suggest a single screening esophagogastroduodenoscopy (EGD) in patients with multiple risk factors for Barrett's esophagus (BE). We aimed to determine BE prevalence and predictors on repeat EGD after a negative initial EGD, using 2 large national databases (GI Quality Improvement Consortium [GIQuIC] and TriNetX). METHODS: Patients who underwent at least 2 EGDs were included and those with BE or esophageal adenocarcinoma detected at initial EGD were excluded. Patient demographics and prevalence of BE on repeat EGD were collected. Multivariate logistic regression was performed to assess for independent risk factors for BE detected on the repeat EGD. RESULTS: In 214,318 and 153,445 patients undergoing at least 2 EGDs over a median follow-up of 28-35 months, the prevalence of BE on repeat EGD was 1.7% in GIQuIC and 3.4% in TriNetX, respectively (26%-45% of baseline BE prevalence). Most (89%) patients had nondysplastic BE. The prevalence of BE remained stable over time (from 1 to >5 years from negative initial EGD) but increased with increasing number of risk factors. BE prevalence in a high-risk population (gastroesophageal reflux disease plus ≥1 risk factor for BE) was 3%-4%. CONCLUSIONS: In this study of >350,000 patients, rates of BE on repeat EGD ranged from 1.7%-3.4%, and were higher in those with multiple risk factors. Most were likely missed at initial evaluation, underscoring the importance of a high-quality initial endoscopic examination. Although routine repeat endoscopic BE screening after a negative initial examination is not recommended, repeat screening may be considered in carefully selected patients with gastroesophageal reflux disease and ≥2 risk factors for BE, potentially using nonendoscopic tools.

Algorithm Training and Testing for a Nonendoscopic Barrett's Esophagus Detection Test in Prospective Multicenter Cohorts.

BACKGROUND & AIMS: Endoscopic Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) detection is invasive and expensive. Nonendoscopic BE/EAC detection tools are guideline-endorsed alternatives. We previously described a 5-methylated DNA marker (MDM) panel assayed on encapsulated sponge cell collection device (CCD) specimens. We aimed to train a new algorithm using a 3-MDM panel and test its performance in an independent cohort. METHODS: Algorithm training and test samples were from 2 prospective multicenter cohorts. All BE cases had esophageal intestinal metaplasia (with or without dysplasia/EAC); control subjects had no endoscopic evidence of BE. The CCD procedure was followed by endoscopy. From CCD cell lysates, DNA was extracted, bisulfite treated, and MDMs were blindly assayed. The algorithm was set and locked using cross-validated logistic regression (training set) and its performance was assessed in an independent test set. RESULTS: Training (N = 352) and test (N = 125) set clinical characteristics were comparable. The final panel included 3 MDMs (NDRG4, VAV3, ZNF682). Overall sensitivity was 82% (95% CI, 68%-94%) at 90% (79%-98%) specificity and 88% (78%-94%) sensitivity at 84% (70%-93%) specificity in training and test sets, respectively. Sensitivity was 90% and 68% for all long- and short-segment BE, respectively. Sensitivity for BE with high-grade dysplasia and EAC was 100% in training and test sets. Overall sensitivity for nondysplastic BE was 82%. Areas under the receiver operating characteristic curves for BE detection were 0.92 and 0.94 in the training and test sets, respectively. CONCLUSIONS: A locked 3-MDM panel algorithm for BE/EAC detection using a nonendoscopic CCD demonstrated excellent sensitivity for high-risk BE cases in independent validation samples. (Clinical trials.gov: NCT02560623, NCT03060642.).

Significant Reduction in the Diagnosis of Barrett's Esophagus and Related Dysplasia During the COVID-19 Pandemic.

INTRODUCTION: The coronavirus disease 19 (COVID-19) pandemic disrupted endoscopy practices, creating unprecedented decreases in cancer screening and surveillance services. We aimed to assess the impact of the pandemic on the proportion of patients diagnosed with Barrett's esophagus (BE) and BE-related dysplasia and adherence to established quality indicators. METHODS: Data from all esophagogastroduodenoscopies in the GI Quality Improvement Consortium, a national repository of matched endoscopy and pathology data, were analyzed from January 2018 to December 2022. Four cohorts were created based on procedure date and COVID-19 data: pre-pandemic (January 2018 to February 2020), pandemic-phase I (March 2020 to July 2020), pandemic-phase II (August 2020 to May 2021), and pandemic-phase III (June 2021 to December 2022). Observed and expected number of BE and BE-related dysplasia cases per month and adherence to the Seattle biopsy protocol and recommended surveillance intervals for nondysplastic BE (NDBE) were evaluated. RESULTS: Among 2,446,857 esophagogastroduodenoscopies performed during the study period, 104,124 (4.3%) had pathology-confirmed BE. The histologic distribution was 87.4% NDBE, 1.8% low-grade dysplasia, 2.4% indefinite for dysplasia, and 1.4% high-grade dysplasia. The number of monthly BE (-47.9% pandemic-phase I, -21.5% pandemic-phase II, and -19.0% pandemic-phase III) and BE-related dysplasia (high-grade dysplasia: 41.2%, -27.7%, and -19.0%; low-grade dysplasia: 49.1%, -35.3%, and -26.5%; any dysplasia: 46.7%, -32.3%, and -27.9%) diagnoses were significantly reduced during the pandemic phases compared with pre-pandemic data. Adherence rates to the Seattle protocol and recommended surveillance intervals for NDBE did not decline during the pandemic. DISCUSSION: There was a significant decline in the number of BE and BE-related dysplasia diagnoses during the COVID-19 pandemic, with an approximately 50% reduction in the number of cases of dysplasia diagnosed in the early pandemic. The absence of a compensatory increase in diagnoses in the pandemic-phase II and III periods may result in deleterious downstream effects on esophageal adenocarcinoma morbidity and mortality.

Rates of Recurrent Intestinal Metaplasia and Dysplasia After Successful Endoscopic Therapy of Barrett's Neoplasia by Endoscopic Mucosal Resection vs Endoscopic Submucosal Dissection and Ablation: A Large North American Multicenter Cohort.

INTRODUCTION: Endoscopic eradication therapy (EET) combining endoscopic resection (ER) with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) followed by ablation is the standard of care for the treatment of dysplastic Barrett's esophagus (BE). We have previously shown comparable rates of complete remission of intestinal metaplasia (CRIM) with both approaches. However, data comparing recurrence after CRIM are lacking. We compared rates of recurrence after CRIM with both techniques in a multicenter cohort. METHODS: Patients undergoing EET achieving CRIM at 3 academic institutions were included. Demographic and clinical data were abstracted. Outcomes included rates and predictors of any BE and dysplastic BE recurrence in the 2 groups. Cox-proportional hazards models and inverse probability treatment weighting (IPTW) analysis were used for analysis. RESULTS: A total of 621 patients (514 EMR and 107 ESD) achieving CRIM were included in the recurrence analysis. The incidence of any BE (15.7, 5.7 per 100 patient-years) and dysplastic BE recurrence (7.3, 5.3 per 100 patient-years) were comparable in the EMR and ESD groups, respectively. On multivariable analyses, the chances of BE recurrence were not influenced by ER technique (hazard ratio 0.87; 95% confidence interval 0.51-1.49; P = 0.62), which was also confirmed by IPTW analysis (ESD vs EMR: hazard ratio 0.98; 95% confidence interval 0.56-1.73; P = 0.94). BE length, lesion size, and history of cigarette smoking were independent predictors of BE recurrence. DISCUSSION: Patients with BE dysplasia/neoplasia achieving CRIM, initially treated with EMR/ablation, had comparable recurrence rates to ESD/ablation. Randomized trials are needed to confirm these outcomes between the 2 ER techniques.

Multicenter, Prospective Trial of Nonendoscopic Biomarker-Driven Detection of Barrett's Esophagus and Esophageal Adenocarcinoma.

INTRODUCTION: Preliminary data suggest that an encapsulated balloon (EsoCheck), coupled with a 2 methylated DNA biomarker panel (EsoGuard), detects Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) with high accuracy. The initial assay requires sample freezing upon collection. The purpose of this study was to assess a next-generation EsoCheck sampling device and EsoGuard assay in a much-enlarged multicenter study clinically enhanced by using a Clinical Laboratory Improvement Amendments of 1988-compliant assay and samples maintained at room temperature. METHODS: Cases with nondysplastic BE (NDBE), dysplastic BE (indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia), EAC, junctional adenocarcinoma, plus endoscopy controls without esophageal intestinal metaplasia, were prospectively enrolled. Medical assistants at 6 institutions delivered the encapsulated balloon per orally with inflation in the stomach. The inflated balloon sampled the distal 5 cm of the esophagus and then was deflated and retracted into the capsule, preventing sample contamination. EsoGuard bisulfite sequencing assayed levels of methylated vimentin and methylated cyclin A1. RESULTS: A total of 243 evaluable patients-88 cases (median age 68 years, 78% men, 92% White) and 155 controls (median age 57 years, 41% men, 88% White)-underwent adequate EsoCheck sampling. The mean procedural time was approximately 3 minutes. Cases included 31 with NDBE, 16 with indefinite for dysplasia/low-grade dysplasia, 23 with high-grade dysplasia, and 18 with EAC/junctional adenocarcinoma. Thirty-seven NDBE and dysplastic BE cases (53%) were short-segment BE (<3 cm). Overall sensitivity was 85% (95% confidence interval 0.78-0.93) and specificity was 85% (95% confidence interval 0.79-0.90). Sensitivity for NDBE was 84%. EsoCheck/EsoGuard detected 100% of cancers (n = 18). DISCUSSION: EsoCheck/EsoGuard demonstrated high sensitivity and specificity in detecting BE and BE-related neoplasia.

Clinical Outcomes After Endoscopic Management of Low-Risk and High-Risk T1a Esophageal Adenocarcinoma: A Multicenter Study.

INTRODUCTION: Endoscopic eradication therapy (EET) is standard of care for T1a esophageal adenocarcinoma (EAC). However, data on outcomes in high-risk T1a EAC are limited. We assessed and compared outcomes after EET of low-risk and high-risk T1a EAC, including intraluminal EAC recurrence, extraesophageal metastases, and overall survival. METHODS: Patients who underwent EET for T1a EAC at 3 referral Barrett's esophagus endotherapy units between 1996 and 2022 were included. Patients with submucosal invasion, positive deep margins, or metastases at initial diagnosis were excluded. High-risk T1a EAC was defined as T1a EAC with poor differentiation and/or lymphovascular invasion, with low-risk disease being defined without these features. All pathology was systematically assessed by expert gastrointestinal pathologists. Baseline and follow-up endoscopy and pathology data were abstracted. Time-to-event analyses were performed to compare outcomes between groups. RESULTS: One hundred eighty-eight patients with T1a EAC were included (high risk, n = 45; low risk, n = 143) with a median age of 70 years, and 84% were men. Groups were comparable for age, sex, Barrett's esophagus length, lesion size, and EET technique. Rates of delayed extraesophageal metastases (11.1% vs 1.4%) were significantly higher in the high-risk group ( P = 0.02). There was no significant difference in the rates of intraluminal EAC recurrence ( P = 0.79) and overall survival ( P = 0.73) between the 2 groups. DISCUSSION: Patients with high-risk T1a EAC undergoing successful EET had a substantially higher rate of extraesophageal metastases compared with those with low-risk T1a EAC on long-term follow-up. These data should be factored into discussions with patients while selecting treatment approaches. Additional prospective data in this area are critical.

Safety of EUS latex balloon use in patients with a latex allergy.

BACKGROUND AND AIMS: Balloons are used in EUS to improve visualization. However, data on the safety of latex balloons in patients with latex allergies are limited, and nonlatex alternatives can be costly. We investigated the safety of latex balloon use during EUS. METHODS: A retrospective review was conducted at a tertiary center between 2019 and 2022. Patients with reported latex allergies who underwent linear EUS were included. Baseline demographics, EUS characteristics, and adverse events were collected. The primary outcome was the rate of adverse events. RESULTS: Eighty-seven procedures were performed on 57 unique patients (mean age, 65.3 ± 14.5 years). Latex balloons were used in 59 procedures (67.8%), with only 8 procedures (13.6%) using prophylactic medications. No adverse events occurred during or after procedures, regardless of medication use or history of anaphylaxis. CONCLUSIONS: The use of EUS latex balloons in patients with a latex allergy was associated with no adverse events.

Stratification of Barrett's esophagus surveillance based on p53 immunohistochemistry: a cost-effectiveness analysis by an international collaborative group.

BACKGROUND: Surveillance of nondysplastic Barrett's esophagus (NDBE) is recommended to identify progression to dysplasia; however, the most cost-effective strategy remains unclear. Mutation of TP53 or aberrant expression of p53 have been associated with the development of dysplasia in BE. We sought to determine if surveillance intervals for BE could be stratified based on p53 expression. METHODS: A Markov model was developed for NDBE. Patients with NDBE underwent p53 immunohistochemistry (IHC) and those with abnormal p53 expression underwent surveillance endoscopy at 1 year, while patients with normal p53 expression underwent surveillance in 3 years. Patients with dysplasia underwent endoscopic therapy and surveillance. RESULTS: On base-case analysis, the strategy of stratifying surveillance based on abnormal p53 IHC was cost-effective relative to conventional surveillance and a natural history model, with an incremental cost-effectiveness ratio (ICER) of $8258 for p53 IHC-based surveillance. Both the conventional and p53-stratified surveillance strategies dominated the natural history model. On probabilistic sensitivity analysis, the p53 IHC strategy ($28 652; 16.78 quality-adjusted life years [QALYs]) was more cost-effective than conventional surveillance ($25 679; 16.17 QALYs) with a net monetary benefit of $306 873 compared with conventional surveillance ($297 642), with an ICER <$50 000 in 96% of iterations. The p53-stratification strategy was associated with a 14% reduction in the overall endoscopy burden and a 59% increase in dysplasia detection. CONCLUSION: A surveillance strategy for BE based on abnormal p53 IHC is cost-effective relative to a conventional surveillance strategy and is likely to be associated with higher rates of dysplasia diagnosis.

A Delphi Method for Development of a Barrett's Esophagus Question Prompt List as a Communication Tool for Optimal Patient-physician Communication.

BACKGROUND METHODS: The question prompt list content was derived through a modified Delphi process consisting of 3 rounds. In round 1, experts provided 5 answers to the prompts "What general questions should patients ask when given a new diagnosis of Barrett's esophagus" and "What questions do I not hear patients asking, but given my expertise, I believe they should be asking?" Questions were reviewed and categorized into themes. In round 2, experts rated questions on a 5-point Likert scale. In round 3, experts rerated questions modified or reduced after the previous rounds. Only questions rated as "essential" or "important" were included in Barrett's esophagus question prompt list (BE-QPL). To improve usability, questions were reduced to minimize redundancy and simplified to use language at an eighth-grade level (Fig. 1). RESULTS: Twenty-one esophageal medical and surgical experts participated in both rounds (91% males; median age 52 years). The expert panel comprised of 33% esophagologists, 24% foregut surgeons, and 24% advanced endoscopists, with a median of 15 years in clinical practice. Most (81%), worked in an academic tertiary referral hospital. In this 3-round Delphi technique, 220 questions were proposed in round 1, 122 (55.5%) were accepted into the BE-QPL and reduced down to 76 questions (round 2), and 67 questions (round 3). These 67 questions reached a Flesch Reading Ease of 68.8, interpreted as easily understood by 13 to 15 years olds. CONCLUSIONS: With multidisciplinary input, we have developed a physician-derived BE-QPL to optimize patient-physician communication. Future directions will seek patient feedback to distill the questions further to a smaller number and then assess their usability.

Synthesis of Di(thiophen-2-yl) Substituted Pyrene-Pyridine Conjugated Scaffold and DFT Insights: A Selective and Sensitive Colorimetric, and Ratiometric Fluorescent Sensor for Fe(III) Ions.

In this context, we used the multicomponent Chichibabin pyridine synthesis reaction to synthesize a novel di(thiophen-2-yl) substituted and pyrene-pyridine fluorescent molecular hybrid. The computational (DFT and TD-DFT) and experimental investigations were performed to understand the photophysical properties of the synthesized new structural scaffold. The synthesized ligand displays highly selective fluorescent sensing properties towards Fe3+ ions when compared to other competitive metal ions (Al3+, Ba2+, Ca2+, Cd2+, Co2+, Cr3+, Cu2+, Fe2+, Hg2+, Na+, Ni2+, Pb2+, Sr2+, Sn2+ and Zn2+). The photophysical properties studies reveal that the synthesized hybrid molecule has a binding constant of 2.30 × 103 M-1 with limit of detection (LOD) of 4.56 × 10-5 M (absorbance mode) and 5.84 × 10-5 M (emission mode) for Fe3+ ions. We believe that the synthesized pyrene-conjugated hybrid ligand can serve as a potential fluorescent chemosensor for the selective and specific detection of Fe3+ ions.

Population Based Time Trends in the Epidemiology and Mortality of Gastroesophageal Junction and Esophageal Adenocarcinoma.

BACKGROUND: Limited data are available on the epidemiology of gastroesophageal junction adenocarcinoma (GEJAC), particularly in comparison to esophageal adenocarcinoma (EAC). With the advent of molecular non-endoscopic Barrett's esophagus (BE) detection tests which sample the esophagus and gastroesophageal junction, early detection of EAC and GEJAC has become a possibility and their epidemiology has gained importance. AIMS: We sought to evaluate time trends in the epidemiology and survival of patients with EAC and GEJAC in a population-based cohort. METHODS: EAC and GEJAC patients from 1976 to 2019 were identified using ICD 9 and 10 diagnostic codes from the Rochester Epidemiology Project (REP). Clinical data and survival status were abstracted. Poisson regression was used to calculate incidence rate ratios (IRR). Survival analysis and Cox proportional models were used to assess predictors of survival. RESULTS: We included 443 patients (287 EAC,156 GEJAC). The incidence of EAC and GEJAC during 1976-2019 was 1.40 (CI 1.1-1.74) and 0.83 (CI 0.61-1.11) per 100,000 people, respectively. There was an increase in the incidence of EAC (IRR = 2.45, p = 0.011) and GEJAC (IRR = 3.17, p = 0.08) from 2000 to 2004 compared to 1995-1999, plateauing in later time periods. Most patients had associated BE and presented at advanced stages, leading to high 5-year mortality rates (66% in EAC and 59% in GEJAC). Age and stage at diagnosis were predictors of mortality. CONCLUSION: The rising incidence of EAC/GEJAC appears to have plateaued somewhat in the last decade. However, both cancers present at advanced stages with persistently poor survival, underscoring the need for early detection.

Multifocal atypical teratoid/rhabdoid tumour in an infant-a rare case report.

BACKGROUND: Atypical teratoid/rhabdoid tumours (AT/RT) are uncommon but aggressive, malignant tumours in the paediatric age group. Presentation of concomitant supratentorial and infratentorial lesions in an infant is extremely rare. We discuss an infant diagnosed with such lesions. Systematic PubMed search was conducted using keywords 'atypical teratoid /rhabdoid tumor', 'paediatric' and 'multifocal'. Reports were included for patients younger than 18 years with two or more lesions. The search yielded additional five cases and were tabulated. Age, sex, location, treatment given and survival/outcome were noted. CASE REPORT: A 10-month-old child presented with complaints of drowsiness and intractable vomiting. Imaging showed multifocal supra- and infratentorial lesions with obstructive hydrocephalus. The child underwent ventriculoperitoneal shunt followed by surgical removal of the posterior fossa lesion. Histopathological features were consistent with AT/RT. CONCLUSIONS: Multifocal AT/RT are very rare. The impact of multifocality in the outcome is not known as very few reports are available. Newer targeted therapies may offer insight in improving outcomes in the future.

Hypertension and Kidney Function After Living Kidney Donation.

Importance: Recent guidelines call for better evidence on health outcomes after living kidney donation. Objective: To determine the risk of hypertension in normotensive adults who donated a kidney compared with nondonors of similar baseline health. Their rates of estimated glomerular filtration rate (eGFR) decline and risk of albuminuria were also compared. Design, Setting, and Participants: Prospective cohort study of 924 standard-criteria living kidney donors enrolled before surgery and a concurrent sample of 396 nondonors. Recruitment occurred from 2004 to 2014 from 17 transplant centers (12 in Canada and 5 in Australia); follow-up occurred until November 2021. Donors and nondonors had the same annual schedule of follow-up assessments. Inverse probability of treatment weighting on a propensity score was used to balance donors and nondonors on baseline characteristics. Exposure: Living kidney donation. Main Outcomes and Measures: Hypertension (systolic blood pressure [SBP] ≥140 mm Hg, diastolic blood pressure [DBP] ≥90 mm Hg, or antihypertensive medication), annualized change in eGFR (starting 12 months after donation/simulated donation date in nondonors), and albuminuria (albumin to creatinine ratio ≥3 mg/mmol [≥30 mg/g]). Results: Among the 924 donors, 66% were female; they had a mean age of 47 years and a mean eGFR of 100 mL/min/1.73 m2. Donors were more likely than nondonors to have a family history of kidney failure (464/922 [50%] vs 89/394 [23%], respectively). After statistical weighting, the sample of nondonors increased to 928 and baseline characteristics were similar between the 2 groups. During a median follow-up of 7.3 years (IQR, 6.0-9.0), in weighted analysis, hypertension occurred in 161 of 924 donors (17%) and 158 of 928 nondonors (17%) (weighted hazard ratio, 1.11 [95% CI, 0.75-1.66]). The longitudinal change in mean blood pressure was similar in donors and nondonors. After the initial drop in donors' eGFR after nephrectomy (mean, 32 mL/min/1.73 m2), donors had a 1.4-mL/min/1.73 m2 (95% CI, 1.2-1.5) per year lesser decline in eGFR than nondonors. However, more donors than nondonors had an eGFR between 30 and 60 mL/min/1.73 m2 at least once in follow-up (438/924 [47%] vs 49/928 [5%]). Albuminuria occurred in 132 of 905 donors (15%) and 95 of 904 nondonors (11%) (weighted hazard ratio, 1.46 [95% CI, 0.97-2.21]); the weighted between-group difference in the albumin to creatinine ratio was 1.02 (95% CI, 0.88-1.19). Conclusions and Relevance: In this cohort study of living kidney donors and nondonors with the same follow-up schedule, the risks of hypertension and albuminuria were not significantly different. After the initial drop in eGFR from nephrectomy, donors had a slower mean rate of eGFR decline than nondonors but were more likely to have an eGFR between 30 and 60 mL/min/1.73 m2 at least once in follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT00936078.

Prevalence of Barrett's Esophagus and Esophageal Adenocarcinoma With and Without Gastroesophageal Reflux: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Although gastroesophageal reflux disease (GERD) symptoms are an essential criterion for Barrett's esophagus (BE) screening in most gastroenterology society guidelines, a significant proportion of BE and esophageal adenocarcinoma (EAC) cases do not endorse them. In a systematic review and meta-analysis, we aimed to study the prevalence of BE/EAC in those with and without GERD. METHODS: A systematic search was conducted through 5 major databases for studies reporting prevalence of BE/EAC in patients with and without GERD. Pooled proportions and odds ratios (ORs) of BE, long-segment BE, short-segment BE, dysplasia, and EAC in patients with and without GERD were synthesized. RESULTS: Forty-three articles (12,883 patients with GERD; 51,350 patients without GERD) were included in the final analysis. BE prevalence was 7% (95% confidence interval [CI], 5.8%-8.5%) and 2.2% (95% CI, 1.6%-3%) among individuals with and without GERD, respectively. EAC prevalence was 0.6% (95% CI, 0.4%-1%) and 0.1% (95% CI, 0%-0.2%) in those with and without GERD, respectively. The overall risks for BE (OR, 2.91; 95% CI, 2.06-4.11) and long-segment BE (OR,4.17; 95% CI, 1.78-9.77) were higher in patients with GERD, but the risk for short-segment BE (OR, 1.77; 95% CI, 0.89-3.52) did not differ between the two groups. In 9 population-based high-quality studies (2244 patients with GERD; 3724 patients without GERD), BE prevalence in patients without GERD was 4.9% (95% CI, 2.6%-9%). BE prevalence was highest in North American studies (10.6% [GERD] and 4.8% [non-GERD]). CONCLUSIONS: BE prevalence in those without GERD is substantial, particularly in large high-quality population-based studies. These data are important to factor in future BE/EAC early detection guidelines.

Rio de Janeiro Global Consensus on Landmarks, Definitions, and Classifications in Barrett's Esophagus: World Endoscopy Organization Delphi Study.

BACKGROUND & AIMS: Despite the significant advances made in the diagnosis and treatment of Barrett's esophagus (BE), there is still a need for standardized definitions, appropriate recognition of endoscopic landmarks, and consistent use of classification systems. Current controversies in basic definitions of BE and the relative lack of anatomic knowledge are significant barriers to uniform documentation. We aimed to provide consensus-driven recommendations for uniform reporting and global application. METHODS: The World Endoscopy Organization Barrett's Esophagus Committee appointed leaders to develop an evidence-based Delphi study. A working group of 6 members identified and formulated 23 statements, and 30 internationally recognized experts from 18 countries participated in 3 rounds of voting. We defined consensus as agreement by ≥80% of experts for each statement and used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool to assess the quality of evidence and the strength of recommendations. RESULTS: After 3 rounds of voting, experts achieved consensus on 6 endoscopic landmarks (palisade vessels, gastroesophageal junction, squamocolumnar junction, lesion location, extraluminal compressions, and quadrant orientation), 13 definitions (BE, hiatus hernia, squamous islands, columnar islands, Barrett's endoscopic therapy, endoscopic resection, endoscopic ablation, systematic inspection, complete eradication of intestinal metaplasia, complete eradication of dysplasia, residual disease, recurrent disease, and failure of endoscopic therapy), and 4 classification systems (Prague, Los Angeles, Paris, and Barrett's International NBI Group). In round 1, 18 statements (78%) reached consensus, with 12 (67%) receiving strong agreement from more than half of the experts. In round 2, 4 of the remaining statements (80%) reached consensus, with 1 statement receiving strong agreement from 50% of the experts. In the third round, a consensus was reached on the remaining statement. CONCLUSIONS: We developed evidence-based, consensus-driven statements on endoscopic landmarks, definitions, and classifications of BE. These recommendations may facilitate global uniform reporting in BE.

Patients With Esophageal Adenocarcinoma With Prior Gastroesophageal Reflux Disease Symptoms Are Similar to Those Without Gastroesophageal Reflux Disease: A Cross-Sectional Study.

INTRODUCTION: A substantial proportion of patients with esophageal adenocarcinoma (EAC) do not report gastroesophageal reflux disease (GERD) symptoms. This study aimed to compare the risk factor profiles and cancer stage at presentation of patients with EAC with and without prior GERD. METHODS: In this retrospective cross-sectional study, patients with EAC were divided into 2 cohorts: (i) EAC with prior GERD: patients who reported typical GERD symptoms (heartburn or regurgitation) ≥1 year before cancer diagnosis and (ii) EAC without prior GERD: patients who did not report prior GERD symptoms or reported symptoms within 1 year of their cancer diagnosis. Baseline demographics, risk factors, and cancer stage at presentation were compared between the 2 cohorts. In addition, the distribution of patients based on numbers of BE/EAC-associated risk factors (1, 2, 3, 4, and 5 or more) was examined in the symptomatic and asymptomatic cohorts. RESULTS: Over 13 years, 388 patients with EAC with prior GERD and 245 patients with EAC without prior GERD were recruited. Both groups had similar baseline demographics and risk factors, but patients with EAC with prior GERD were more likely to have a history of BE. Asymptomatic patients had more advanced disease. Patients with 3 or more BE/EAC-related risk factors formed the largest proportion of patients in both the symptomatic and asymptomatic cohorts. DISCUSSION: Patients with EAC with and without prior GERD symptoms are phenotypically similar, suggesting that BE screening efforts to prevent or detect early EAC should not be restricted to just those with GERD.