Social disparities in delivery choice among patients with history of cesarean.

OBJECTIVE: Given the call to reduce rates of non-medically indicated cesarean deliveries (CDs) by encouraging trials of labor after cesarean (TOLAC), this study looks at social characteristics of patients choosing a TOLAC versus a scheduled repeat cesarean delivery (SRCD) to determine disparities regarding delivery method choice. METHODS: This was a retrospective cohort study of patients with a history of one CD between April 29, 2015-April 29, 2020. Patients were divided based on type of delivery chosen at admission. Chi-squared tests examined proportional differences between groups and logistic regression models examined odd ratios of choosing TOLAC versus SRCD according to socially dependent categories including race/ethnicity, health insurance, pre-pregnancy body mass index, and Social Vulnerability Index (SVI). RESULTS: 1,983 patients were included. Multivariable logistic regression models revealed that patients with a high SVI (reference: low/medium SVI) (AOR 2.0, CI: 1.5, 2.5), self-identified as Black/ African American (AOR: 2.4, CI: 1.6, 3.6) or Hispanic/Latina (AOR: 2.0, CI: 1.4, 2.8) (reference: White), had public insurance (reference: private insurance) (AOR: 3.7, CI: 2.8, 5.0), and who had an obese BMI (reference: non-obese BMI) were more likely to opt for a TOLAC rather than SRCD. CONCLUSION: These findings demonstrate differences in delivery method preferences. Specifically, more disadvantaged patients are more likely to choose TOLAC, suggesting that social and economic factors may play a role in delivery preferences. These findings have implications for improving individualized counselling and engaging in shared decision-making around mode of delivery.

Is There Utility in Transvaginal Cervical Length Surveillance After Cerclage Placement for the Prediction of Spontaneous Preterm Birth?

INTRODUCTION: Transvaginal cervical length (TVCL) surveillance post-transvaginal cerclage placement is not universally performed, despite the correlated risk of short TVCL with spontaneous preterm birth (sPTB). This study evaluated if patients with a TVCL <2.5 cm after cerclage placement had higher odds of sPTB than those with a TVCL ≥2.5 cm after cerclage placement. METHODS: This retrospective cohort study included patients with a singleton, non-anomalous gestation with a transvaginal cerclage who had TVCL surveillance post-cerclage placement. The primary outcome was the odds of sPTB among patients with TVCL <2.5 cm vs TVCL ≥2.5 cm after cerclage placement. Transvaginal cerclage placement indications included history indicated, physical exam indicated, and ultrasound indicated. Outcomes were assessed using univariate and multivariate analysis while adjusting for progesterone use, TVCL before cerclage placement, and cerclage indication. RESULTS: The analysis included 210 patients, and the sPTB rate was 46.7%. Those with sPTB underwent cerclage placement at later gestational ages, had higher rates of exam-indicated cerclage, and were more likely to be prescribed vaginal progesterone. Patients with a TVCL of <2.5 cm after cerclage placement did not have significantly increased odds of sPTB (OR: 2.8, 95% CI: 0.9-8.7, p=0.07); however, patients with a TVCL <2.0 cm had significantly increased odds of sPTB (OR: 6.3, 95% CI: 2.2-18.8, p<0.001). CONCLUSION: In patients with transvaginal cerclage, there does not appear to be increased odds of sPTB with TVCL <2.5 cm after cerclage placement; however, there does appear to be an increased odds of sPTB in patients with a TVCL of <2.0 cm after cerclage placement.

SARS-CoV-2 Seropositivity in Urban Population of Wild Fallow Deer, Dublin, Ireland, 2020-2022.

SARS-CoV-2 can infect wildlife, and SARS-CoV-2 variants of concern might expand into novel animal reservoirs, potentially by reverse zoonosis. White-tailed deer and mule deer of North America are the only deer species in which SARS-CoV-2 has been documented, raising the question of whether other reservoir species exist. We report cases of SARS-CoV-2 seropositivity in a fallow deer population located in Dublin, Ireland. Sampled deer were seronegative in 2020 when the Alpha variant was circulating in humans, 1 deer was seropositive for the Delta variant in 2021, and 12/21 (57%) sampled deer were seropositive for the Omicron variant in 2022, suggesting host tropism expansion as new variants emerged in humans. Omicron BA.1 was capable of infecting fallow deer lung type-2 pneumocytes and type-1-like pneumocytes or endothelial cells ex vivo. Ongoing surveillance to identify novel SARS-CoV-2 reservoirs is needed to prevent public health risks during human-animal interactions in periurban settings.

SARS-CoV-2 infects neurons, astrocytes, choroid plexus epithelial cells and pericytes of the human central nervous system in vitro.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with neurological sequelae including haemorrhage, thrombosis and ischaemic necrosis and encephalitis. However, the mechanism by which this occurs is unclear. Neurological disease associated with COVID-19 has been proposed to occur following direct infection of the central nervous system and/or indirectly by local or systemic immune activation. We evaluated the expression of angiotensin-converting enzyme-2 and transmembrane protease, serine 2 (TMPRSS2) in brain tissue from five healthy human donors and observed low-level expression of these proteins in cells morphologically consistent with astrocytes, neurons and choroidal ependymal cells within the frontal cortex and medulla oblongata. Primary human astrocytes, neurons, choroid plexus epithelial cells and pericytes supported productive SARS-CoV-2 infection with ancestral, Alpha, Delta and Omicron variants. Infected cells supported the full viral life cycle, releasing infectious virus particles. In contrast, primary brain microvascular endothelial cells and microglia were refractory to SARS-CoV-2 infection. These data support a model whereby SARS-CoV-2 can infect human brain cells, and the mechanism of viral entry warrants further investigation.

Decay of RNA and infectious SARS-CoV-2 and murine hepatitis virus in wastewater.

Wastewater-based epidemiology (WBE) has been an important tool for population surveillance during the COVID-19 pandemic and continues to play a key role in monitoring SARS-CoV-2 infection levels following reductions in national clinical testing schemes. Studies measuring decay profiles of SARS-CoV-2 in wastewater have underscored the value of WBE, however investigations have been hampered by high biosafety requirements for SARS-CoV-2 infection studies. Therefore, surrogate viruses with lower biosafety standards have been used for SARS-CoV-2 decay studies, such as murine hepatitis virus (MHV), but few studies have directly compared decay rates of both viruses. We compared the persistence of SARS-CoV-2 and MHV in wastewater, using 50 % tissue culture infectious dose (TCID50) and reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays to assess infectious virus titre and viral gene markers, respectively. Infectious SARS-CoV-2 and MHV indicate similar endpoints, however observed early decay characteristics differed, with infectious SARS-CoV-2 decaying more rapidly than MHV. We find that MHV is an appropriate infectious virus surrogate for viable SARS-CoV-2, however inconsistencies exist in viral RNA decay parameters, indicating MHV may not be a suitable nucleic acid surrogate across certain temperature regimes. This study highlights the importance of sample preparation and the potential for decay rate overestimation in wastewater surveillance for SARS-CoV-2 and other pathogens.

Synthesis and in Vitro Evaluation of CAPE Derivatives as Ferroptosis Inducers in Triple Negative Breast Cancer.

Herein, we describe the design, synthesis, and in vitro biological evaluation of HO-1 inducers endowed with cytotoxic effects mediated by ferroptosis activation. Using the natural HO-1 inducer caffeic acid phenethyl ester (CAPE) as a chemical scaffold, new derivatives were synthesized by performing modifications in the cathecol moiety and in the phenethyl ester aromatic ring. Biological assays aimed at evaluating an imbalanced activity of ferroptosis key players identified that 2-(1H-indol-3-yl)ethyl cinnamate (compound 24) possesses improved anticancer activity toward the MDA-MB 231 triple negative breast cancer cell line when compared to CAPE. Increased ROS and LOOH levels, reduced GSH levels, imbalanced mitochondrial activity, and restored cell viability after ferrostatin-1 treatment suggested a ferroptotic mechanism of action, which did not involve GPX4 inhibition. Compound 24 represents an intriguing hit compound useful for the identification of novel ferroptosis inducers.

Adjusting models to better predict obstetric anal sphincter injury (OASIS) in forceps-assisted vaginal deliveries: A retrospective cross-sectional trial.

OBJECTIVE: Obesity and maternal age are increasing among pregnant patients. The understood effect of body mass index (BMI), advanced maternal age (AMA), and second stage of labor on obstetric anal sphincter injury (OASIS) at delivery is varied. The objective of this study was to assess whether incorporating BMI, second stage of labor length, and AMA into a model for predicting OASIS among forceps-assisted vaginal deliveries (FAVD) had a higher predictivity value compared to models without these additions. METHOD: This was an IRB-approved retrospective cohort study of singleton gestations who underwent a FAVD between 2017 and 2021. The primary outcome was prediction of OASIS via established models versus models including the addition of new predictive factors. RESULTS: A total of 979 patients met inclusionary criteria and were included in the final analysis. 20.4% of patients had an OASIS laceration, 11.3% of neonates had NICU admissions, 23.7% had a composite all neonatal outcome, and 8% had a composite subgaleal/cephalohematoma outcome. Comparisons of known factors that predict OASIS (nulliparity, race, episiotomy status) to known factors with additional predictors (BMI, AMA, and length of second stage in labor) were explored. After comparing each model's AUC to one another (a total of 3 comparisons made), there was no statistically significant difference between the models (all P > 0.62). CONCLUSION: Including BMI, AMA, and second stage of labor length does not improve the predictivity of OASIS in patients with successful FAVD. These factors should not impact a provider's decision to perform a FAVD when solely considering increased odds of OASIS.

Examining provider practice-level disparities in delivery outcomes among patients with a history of Cesarean Delivery.

BACKGROUND: Choosing whether to pursue a trial of labor after cesarean (TOLAC) or scheduled repeat cesarean delivery (SRCD) requires prenatal assessment of risks and benefits. Providers and patients play a central role in this process. However, the influence of provider-associated characteristics on delivery methods remains unclear. We hypothesized that different provider practice groups have different obstetric outcomes in patients with one prior cesarean delivery (CD). METHODS: This was a retrospective cohort study of deliveries between April 29, 2015 - April 29, 2020. Subjects were divided into three cohorts: SRCD, successful VBAC, and unsuccessful VBAC (patients who chose TOLAC but had a CD). Disparities were reviewed between five different obstetric provider practice groups, determined from a breakdown of different providers delivering at the study site during the study period. Proportional differences were examined using Chi-squared tests and logistic regression models. RESULTS: 1,439 deliveries were included in the study. There were significant proportional disparities between patients in the different groups. Specifically, patients from Group D were significantly more likely to undergo successful VBAC, while patients seeing a provider from Group A were more likely to deliver by SRCD. In our multivariate analysis of successful versus unsuccessful VBAC, patients from Group D had greater odds ratios of successful VBAC compared to Group A. Patients delivered by Group E had a significantly lower odds ratio of successful VBAC. CONCLUSION: This study suggests an association between provider practice groups and delivery outcomes among patients with one prior CD. These data contribute to a growing body of literature around patient choice in pregnancy and the interplay of patients and providers. These findings help to guide future investigations to improve outcomes among patients with a history of CD.

MASCOT-Skyline integrates population and migration dynamics to enhance phylogeographic reconstructions.

The spread of infectious diseases is shaped by spatial and temporal aspects, such as host population structure or changes in the transmission rate or number of infected individuals over time. These spatiotemporal dynamics are imprinted in the genome of pathogens and can be recovered from those genomes using phylodynamics methods. However, phylodynamic methods typically quantify either the temporal or spatial transmission dynamics, which leads to unclear biases, as one can potentially not be inferred without the other. Here, we address this challenge by introducing a structured coalescent skyline approach, MASCOT-Skyline that allows us to jointly infer spatial and temporal transmission dynamics of infectious diseases using Markov chain Monte Carlo inference. To do so, we model the effective population size dynamics in different locations using a non-parametric function, allowing us to approximate a range of population size dynamics. We show, using a range of different viral outbreak datasets, potential issues with phylogeographic methods. We then use these viral datasets to motivate simulations of outbreaks that illuminate the nature of biases present in the different phylogeographic methods. We show that spatial and temporal dynamics should be modeled jointly even if one seeks to recover just one of the two. Further, we showcase conditions under which we can expect phylogeographic analyses to be biased, particularly different subsampling approaches, as well as provide recommendations of when we can expect them to perform well. We implemented MASCOT-Skyline as part of the open-source software package MASCOT for the Bayesian phylodynamics platform BEAST2.

Local-scale phylodynamics reveal differential community impact of SARS-CoV-2 in a metropolitan US county.

SARS-CoV-2 transmission is largely driven by heterogeneous dynamics at a local scale, leaving local health departments to design interventions with limited information. We analyzed SARS-CoV-2 genomes sampled between February 2020 and March 2022 jointly with epidemiological and cell phone mobility data to investigate fine scale spatiotemporal SARS-CoV-2 transmission dynamics in King County, Washington, a diverse, metropolitan US county. We applied an approximate structured coalescent approach to model transmission within and between North King County and South King County alongside the rate of outside introductions into the county. Our phylodynamic analyses reveal that following stay-at-home orders, the epidemic trajectories of North and South King County began to diverge. We find that South King County consistently had more reported and estimated cases, COVID-19 hospitalizations, and longer persistence of local viral transmission when compared to North King County, where viral importations from outside drove a larger proportion of new cases. Using mobility and demographic data, we also find that South King County experienced a more modest and less sustained reduction in mobility following stay-at-home orders than North King County, while also bearing more socioeconomic inequities that might contribute to a disproportionate burden of SARS-CoV-2 transmission. Overall, our findings suggest a role for local-scale phylodynamics in understanding the heterogeneous transmission landscape.

Application of phylodynamics to identify spread of antimicrobial-resistant Escherichia coli between humans and canines in an urban environment.

The transmission of antimicrobial resistant bacteria in the urban environment is poorly understood. We utilized genomic sequencing and phylogenetics to characterize the transmission dynamics of antimicrobial resistant Escherichia coli (AMR-Ec) cultured from putative canine (caninep) and human feces present on urban sidewalks in San Francisco, California. We isolated a total of fifty-six AMR-Ec isolates from human (n = 20) and caninep (n = 36) fecal samples from the Tenderloin and South of Market (SoMa) neighborhoods of San Francisco. We then analyzed phenotypic and genotypic antimicrobial resistance (AMR) of the isolates, as well as clonal relationships based on cgMLST and single nucleotide polymorphisms (SNPs) of the core genomes. Using Bayesian inference, we reconstructed the transmission dynamics between humans and caninesp from multiple local outbreak clusters using the marginal structured coalescent approximation (MASCOT). Our results provide evidence for multiple sharing events of AMR-Ec between humans and caninesp. In particular, we found one instance of likely transmission from caninesp to humans as well as an additional local outbreak cluster consisting of one caninep and one human sample. Based on this analysis, it appears that non-human feces act as an important reservoir of clinically relevant AMR-Ec within the urban environment for this study population. This work showcases the utility of genomic epidemiology to reconstruct potential pathways by which antimicrobial resistance spreads.

Effects of Combined Endurance and Resistance Eccentric Training on Muscle Function and Functional Performance in Patients With Chronic Obstructive Pulmonary Disease: Randomized Controlled Trial.

OBJECTIVE: To evaluate the adherence to treatment and efficacy of an eccentric-based training (ECC) program on peripheral muscle function and functional exercise capacity in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Prospective, assessor-blinded, randomized controlled trial. SETTING: The cardiopulmonary rehabilitation unit of a tertiary subacute referral center. PARTICIPANTS: Thirty (N=30) stable inpatients (mean age 68±8 years; FEV1 44±18% of predicted) with COPD were included in the study. INTERVENTIONS: Inpatients were randomly assigned to 4 weeks of a combined endurance and resistance ECC (n=15) or conventional training (CON; n=15). MAIN OUTCOME MEASURES: Quadriceps peak torque (PT) was the primary outcome measure for muscle function. Rate of force development (RFD), muscle activation and quality (quadriceps PT/leg lean mass), 6-min walk distance (6MWD), 4-meter gait speed (4mGS), 10-meter gait speed, 5-repetition sit-to-stand (5STS), dyspnea rate, and mortality risk were the secondary outcomes. Evaluations were performed at baseline and repeated after 4 weeks and 3 months of follow-up. RESULTS: Quadriceps PT, RFD, and muscle quality improved by 17±23% (P<.001), 19±24%, and 16±20% (both P<.05) within the ECC group. Besides, a significant between-group difference for RFD (56±94 Nm/s, P=.038) was found after training. Both groups showed clinically relevant improvements in 6MWD, 4mGS, dyspnea rate, and mortality risk, with no significant differences between groups. CONCLUSION: Combined endurance and resistance ECC improved lower limbs muscle function compared with CON in inpatients with COPD. In contrast, ECC did not further improve functional performance, dyspnea, and mortality risk. ECC may be of particular benefit to effect on skeletal muscle function in patients with COPD.

Delivered relative dose intensity in adolescent and young adult germ cell tumours in England: Assessment of data quality and consistency from clinical trials compared to national cancer registration data.

Adolescent and young adults (AYA) with germ cell tumours (GCT) have poorer survival rates than children and many older adults with the same cancers. There are several likely contributing factors to this, including the treatment received. The prognostic benefit of intended dose intensity is well documented in GCT from trials comparing regimens. However, evidence specific to AYA is limited by poor recruitment of AYA to trials and dose delivery outside trials not being well examined. We examined the utility of cancer registration data and a clinical trials dataset to investigate the delivery of relative dose intensity (RDI) in routine National Health Service practice in England, compared to within international clinical trials. Linked data from the Cancer Outcomes and Services Dataset (COSD) and the Systemic Anti-Cancer Therapy (SACT) dataset, and data from four international clinical trials were analysed. Survival over time was described using Kaplan-Meier estimation; overall, by age category, International Germ-Cell Cancer Collaborative Group (IGCCCG) classification, stage, tumour subtype, primary site, ethnicity and deprivation. Cox regression models were used to determine the fully adjusted effect of RDI on mortality risk. The quality of both datasets was critically evaluated and clinically enhanced. RDI was found to be well maintained in all datasets with higher RDIs associated with improved survival outcomes. Real-world data demonstrated several strengths, including population coverage and inclusion of sociodemographic variables and comorbidity. It is limited in GCT however, by the poor completion of data items enabling risk classification of patients and a higher proportion of missing data.

Clostridioides difficile canonical L,D-transpeptidases catalyze a novel type of peptidoglycan cross-links and are not required for beta-lactam resistance.

Clostridioides difficile is the leading cause of antibiotic-associated diarrhea worldwide with significant morbidity and mortality. This organism is naturally resistant to several beta-lactam antibiotics that inhibit the polymerization of peptidoglycan, an essential component of the bacteria cell envelope. Previous work has revealed that C. difficile peptidoglycan has an unusual composition. It mostly contains 3-3 cross-links, catalyzed by enzymes called L,D-transpeptidases (Ldts) that are poorly inhibited by beta-lactams. It was therefore hypothesized that peptidoglycan polymerization by these enzymes could underpin antibiotic resistance. Here, we investigated the catalytic activity of the three canonical Ldts encoded by C. difficile (LdtCd1, LdtCd2, and LdtCd3) in vitro and explored their contribution to growth and antibiotic resistance. We show that two of these enzymes catalyze the formation of novel types of peptidoglycan cross-links using meso-diaminopimelic acid both as a donor and an acceptor, also observed in peptidoglycan sacculi. We demonstrate that the simultaneous deletion of these three genes only has a minor impact on both peptidoglycan structure and resistance to beta-lactams. This unexpected result therefore implies that the formation of 3-3 peptidoglycan cross-links in C. difficile is catalyzed by as yet unidentified noncanonical Ldt enzymes.

Examining Single Session Peer-Teaching Instructional Approaches on Pre-Service Physical Education Teachers' Throwing Techniques.

An important role of a Physical Education (PE) teacher is to assist students to develop the fundamental motor skills (FMS) that will allow them to participate in physical activities with competence and confidence. Thus, PE teachers require the knowledge and skills to carry out this crucial task. In the crowded curricula of Physical Education Teacher Education (PETE) programs, there are limited opportunities for pre-service PE teachers to learn how to analyze and perform a large list of motor skills. Our purposes in this study were to determine whether a single session peer-teaching intervention could improve pre-service PE teachers' short-term non-dominant hand overarm throwing performances and to examine these students' perceptions of the interventions. We allocated 47 pre-service PE teaching students (24 males; 23 females) to one of three experimental groups: a Video Analysis Group (VAG; n = 17), a Verbal Group (VG; n = 19), and a Control Group (CG; n = 11), based on the class in which they were enrolled. VAG and VG participants worked with a partner of their choice in reciprocal peer-teaching to improve each other's non-dominant hand throwing technique. VAG and VG interventions were identical except that VAG participants accessed video analysis technology. CG participants completed unrelated course work that involved no overarm throwing activities. A single 20-minute session of peer teaching with video analysis feedback during practice led to rapid enhancements in non-dominant hand overarm throwing skills. While all three groups improved their performance by retention testing, participants in the VAG group improved most quickly. Participants in both the VAG and VG groups reported that their respective interventions improved their throwing and Qualitative Movement Diagnosis (QMD) skills. Based on these results, we suggest that PETE programs integrate peer-teaching and video analysis sessions into fundamental movement courses to accelerate students' motor skill acquisitions.

Feasibility Study Utilizing NanoString's Digital Spatial Profiling (DSP) Technology for Characterizing the Immune Microenvironment in Barrett's Esophagus Formalin-Fixed Paraffin-Embedded Tissues.

Characterization of the Barrett's esophagus (BE) microenvironment in patients with a known progression status, to determine how it may influence BE progression to esophageal adenocarcinoma (EAC), has been understudied, hindering both the biological understanding of the progression and the development of novel diagnostics and therapies. This study's aim was to determine if a highly multiplex interrogation of the microenvironment can be performed on endoscopic formalin-fixed, paraffin-embedded (FFPE) samples, utilizing the NanoString GeoMx digital spatial profiling (GeoMx DSP) platform and if it can begin to identify the types of immune cells and pathways that may mediate the progression of BE. We performed a spatial proteomic analysis of 49 proteins expressed in the microenvironment and epithelial cells of FFPE endoscopic biopsies from patients with non-dysplastic BE (NDBE) who later progressed to high-grade dysplasia or EAC (n = 7) or from patients who, after at least 5 years follow-up, did not (n = 8). We then performed an RNA analysis of 1812 cancer-related transcripts on three endoscopic mucosal resections containing regions of BE, dysplasia, and EAC. Profiling with GeoMx DSP showed reasonable quality metrics and detected expected differences between epithelium and stroma. Several proteins were found to have an increased expression within NDBE biopsies from progressors compared to non-progressors, suggesting further studies are warranted.

Curcumin I-SMA nanomicelles as promising therapeutic tool to tackle bacterial infections.

Renewed interest towards natural substances has been pushed by the widespread diffusion of antibiotic resistance. Curcumin I is the most active and effective constituent of curcuminoids extracted from Curcuma longa and, among other beneficial effects, attracted attention for its antimicrobial potential. Since the poor pharmacokinetic profile hinders its efficient utilization, in the present paper, we report encapsulation of curcumin I in poly(styrene-co-maleic acid) (SMA-CUR) providing a nanomicellar system with improved aqueous solubility and bioavailability. SMA-CUR was characterized by means of size, zeta potential, polydispersity index, atomic force microscopy (AFM), drug release studies, spectroscopic properties and stability. SMA-CUR nanoformulation displayed exciting antimicrobial properties compared to free curcumin I towards Gram-positive and Gram-negative clinical isolates.

The Tissue Systems Pathology Test Outperforms Pathology Review in Risk Stratifying Patients With Low-Grade Dysplasia.

BACKGROUND & AIMS: Low-grade dysplasia (LGD) is associated with an increased risk of progression in Barrett's esophagus (BE); however, the diagnosis of LGD is limited by substantial interobserver variability. Multiple studies have shown that an objective tissue systems pathology test (TissueCypher Barrett's Esophagus Test, TSP-9), can effectively predict neoplastic progression in patients with BE. This study aimed to compare the risk stratification performance of the TSP-9 test vs benchmarks of generalist and expert pathology. METHODS: A blinded cohort study was conducted in the screening cohort of a randomized controlled trial of patients with BE with community-based LGD. Biopsies from the first endoscopy with LGD were assessed by the TSP-9 test and independently reviewed by 30 pathologists from 5 countries per standard practice. The accuracy of the test and the diagnoses in predicting high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) were compared. RESULTS: A total of 154 patients with BE (122 men), mean age 60.9 ± 9.8 years were studied. Twenty-four patients progressed to HGD/EAC within 5 years (median time of 1.7 years) and 130 did not progress to HGD/EAC within 5 years (median 7.8 years follow-up). The TSP-9 test demonstrated higher sensitivity (71% vs mean 63%, range 33%-88% across 30 pathologists), than the pathology review in detecting patients who progressed (P = .01186). CONCLUSIONS: The TSP-9 test outperformed the pathologists in risk stratifying patients with BE with LGD. Care guided by the test can provide an effective solution to variable pathology review of LGD, improving health outcomes by upstaging care to therapeutic intervention for patients at high risk for progression, while reducing unnecessary interventions in low-risk patients.