Microstructural evolution during the progressive transformation-induced plasticity effect in a Fe-0.1C-5Mnmedium manganese steel

The microstructural evolution of a cold-rolled and intercritical annealed medium-Mn steel(Fe-0.10C-5Mn)was investigated during uniaxial tensile testing.In-situ observations under scanning electron microscopy,transmission electron microscopy,and X-ray diffraction analysis were conducted to characterize the progressive transformation-induced plasticity process and associated fracture initiation mechanisms.These findings were discussed with the local strain measurements via digital image correlation.The results indicated that Lüders band formation in the steel was limited to 1.5%strain,which was mainly due to the early-stage martensitic phase transformation of a very small amount of the less stable large-sized retained austenite(RA),which led to localized stress concentrations and strain hardening and further retardation of yielding.The small-sized RA exhibited high stability and progressively transformed into martensite and contributed to a stably extended Portevin-Le Chatelier effect.The volume fraction of RA gradually decreased from 26.8%to 8.2%prior to fracture.In the late deformation stage,fracture initiation primarily occurred at the austenite/martensite and ferrite/martensite interfaces and the ferrite phase.

Progress in The Application of Nursing Care Based on ERAS Concept after Thoracolumbar Fracture Surgery

Thoracic spine fracture is a common orthopedic injury that is usually caused by external forces acting directly on or transmitted to the thoracic spine through other parts of the spine.Thoracic spine fractures can be divided into two types:stable and unstable.An unstable fracture means that the relationship between the vertebral bodies is no longer stable,which may cause serious consequences such as spinal compression,nerve root compression,or spinal cord injury.Surgical treatment is often needed for patients with unstable fractures,nerve root compression,or spinal cord injury to restore stability and function to the thoracic spine.The probability of complications after thoracolumbar fracture surgery is high,which affects the outcome of surgical treatment.To improve postoperative rehabilitation outcomes,this article analyzed the value of nursing care based on the enhanced recovery after surgery(ERAS)concept for patients undergoing thoracolumbar fracture surgery.

Progress in the Treatment of Thoracolumbar Spinal Fractures with Internal Fixation of Injured Vertebrae with Screws

The thoracolumbar spine,due to its large range of motion and relatively fragile anatomical structure,is prone to traumatic fractures and has become one of the common types of fractures in clinical practice.Thoracic and lumbar fractures may lead to spinal instability,spinal stenosis,etc.,and early restoration of vertebral height and sequence is necessary.Although the technique of transpedicular screw internal fixation for traumatic vertebrae is effective in the short term,in the long run,there may be adverse situations such as fixation breakage and loosening,leading to loss of vertebral height and kyphosis deformity.The technique of internal fixation of injured vertebrae with screws is considered to minimize postoperative complications and is worthy of promotion and use.With the advancement of medical technology,imaging,and biomechanics,the treatment methods for thoracolumbar spinal fractures are becoming increasingly diverse.

Research Progress on Conservative Treatment of Lumbar Disc Herniation

Lumbar disc herniation(LDH)is a common orthopedic disease in clinical practice,with main symptoms of varying degrees of pain and functional impairment,seriously affecting the quality of work and life of patients,and also causing a certain degree of economic burden to the patient's family and society.At present,there are various conservative treatment methods for LDH in clinical practice.Conservative treatment has the characteristics of small trauma and high safety,which can achieve symptom relief and cure for most patients in clinical practice.This article aims to provide a scientific reference for the selection of treatment plans for LDH patients by reviewing relevant literature on conservative treatment of LDH that has been publicly reported both domestically and internationally in recent years.

Kinked Rebar and Engineering Structures Applying Kinked Materials:State-ofthe-Art Review

Kinked rebar is a special type of steel material,which is installed in beam column nodes and frame beams.It effectively enhances the blast resilience,seismic collapse resistance,and progressive collapse resistance of reinforced concrete(RC)structures without imposing substantial cost burdens,thereby emerging as a focal point of recent research endeavors.On the basis of explaining the working principle of kinked rebars,this paper reviews the research status of kinked rebars at home and abroad from three core domains:the tensile mechanical properties of kinked rebars,beam column nodes with kinked rebars,and concrete frame structures with kinked rebars.The analysis underscores that the straightening process of kinked rebars does not compromise their ultimate strength but significantly bolsters structural ductility and enhances energy dissipation capabilities.In beam-column joints,the incorporation of kinked rebars facilitates the seamless transfer of plastic hinges,adhering to the design principle of“strong columns and weak beams.”In addition,kinked rebars can greatly improve the resistance of the beam;The seismic resistance,internal explosion resistance,and progressive collapse resistance of reinforced concrete frame structures with kinked rebar have significantly improved.Beyond its primary application,the principle of kinked rebar was extended to other applications of kinked materials such as corrugated steel plates and origami structures,and the stress characteristics of related components and structures were studied.Intriguingly,this paper also proposes the application of kinked rebars in bridge engineering,aiming to address the challenges of localized damage concentration and excessive residual displacement in RC bridge piers.The introduction of kinked rebars in piers is envisioned to mitigate these issues,with the paper outlining its advantages and feasibility,thereby offering valuable insights for future research on kinked reinforcement and seismic design strategies for bridges.

Internal biliary diversion using appendix during liver transplantation for progressive familial intrahepatic cholestasis type 1:A case report

BACKGROUND Progressive familial intrahepatic cholestasis type 1(PFIC-1)is a genetic cholestatic disease causing end-stage liver disease,which needs liver transplantation(LT).Simultaneous biliary diversion(BD)was recommended to prevent allograft steatosis after transplantation,while increasing the risk of infection.Here,an attempt was made to perform BD using appendix to prevent bacterial translocation after LT.CASE SUMMARY An 11-month-old boy diagnosed with PFIC-1 received ABO compatible living donor LT due to refractory jaundice and pruritus.His mother donated her left lateral segment with a graft-to-recipient weight ratio of 2.9%.Internal BD was constructed during LT using the appendix by connecting its proximal end with the intrahepatic biliary duct and the distal end with colon.Biliary leakage was suspected on the 5th day after transplantation and exploratory laparotomy indicated biliary leakage at the cutting surface of liver.The liver function returned to normal on the 9th day post-operation and maintained normal during the 15-month follow-up.Cholangiography at 10 months after transplantation confirmed the direct secretion of bile into colon.Computerized tomography scan(4 months and 10 months)and liver biopsy(10 months)indicated no steatosis in the allograft.No complaint of recurrent diarrhea,infection or growth retardation was reported during follow-up.CONCLUSION Internal BD using appendix during LT is effective in preventing allograft steatosis and post-transplant infection in PFIC-1 recipients.

Risk factors for neoplastic progression in Barrett's esophagus

Barrett's esophagus (BE) confers a significant increased risk for development of esophageal adenocarcinoma (EAC), with the pathogenesis appearing to progress through a "metaplasia-dysplasia-carcinoma" (MDC) sequence. Many of the genetic insults driving this MDC sequence have recently been characterized, providing targets for candidate biomarkers with potential clinical utility to stratify risk in individual patients. Many clinical risk factors have been investigated, and associations with a variety of genetic, specific gastrointestinal and other modifiable factors have been proposed in the literature. This review summarizes the current understanding of the mechanisms involved in neoplastic progression of BE to EAC and critically appraises the relative roles and contributions of these putative risk factors from the published evidence currently available.

Research Progress of Cymbaria mongolica Maxim.in the Treatment of Chronic Eczema

Chronic eczema is a kind of skin disease which is difficult to treat.It is easy to occur repeatedly,and itching is intolerable during the attack,which seriously affects the daily life of patients.Through the review of the treatment of chronic eczema with Mongolian medicine Cymbaria mongolica Maxim.,it has the advantages of improving the cure rate and the quality of life,and reducing the recurrence rate,and so on,which provides a scientific basis for the promotion and further research of traditional Mongolian medicine Cymbaria mongolica Maxim.

Progress and Problems of Development Research and Application of Sand Barriers

Due to the restrictions on the conditions for afforestation and sand control,the development research,and application of sand barriers have accelerated in recent years,but some problems that cannot be ignored have emerged in practice. In this paper,the functions of wind prevention,sand blocking and fixation,improving soil physical and chemical properties and increasing plant diversity of sand barriers,accretion coefficient and capacity between sand barriers,and mobile sand barriers were analyzed firstly,and then several issues that should be noted in the development and application of sand barriers were proposed. The results show that sand barriers can fix sand on the spot and maintain the stability of sand surface. As an auxiliary measure before afforestation on a mobile sand surface,they are practical and feasible. The biggest drawback of sand barriers is that they are easy to be saturated. Although they can increase plant diversity and surface roughness,they lose the function of blocking sand flow after being saturated,and their function of in-situ sand fixation also rapidly decreases with the degradation of sand barriers. Mobile sand barriers overcome the disadvantage of sand barriers being easy to be saturated to some extent,but the cost greatly increases. In terms of desertification prevention and control by plants,plants are used as sand barriers to study their functions of sand blocking and sand fixation in many researches and practices,but the more important ecological functions of adjusting temperature on sand surface and achieving surface thermodynamic equilibrium of plants are ignored.

Progress in the generation of spinal cord organoids over the past decade and future perspectives

Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo.As emerging bioengineering methods have led to the optimization of cell culture protocols,spinal cord organoids technology has made remarkable advancements in the past decade.Our literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal axes.Moreover,fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional assessment.These qualities make spinal cord organoids valuable tools for disease modeling,drug screening,and tissue regeneration.By utilizing this emergent technology,researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord diseases.However,at present,spinal cord organoid technology remains in its infancy and has not been widely applied in translational medicine.Establishment of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.

Role of exosomal circular RNAs as microRNA sponges and potential targeting for suppressing hepatocellular carcinoma growth and progression

In this editorial,we comment on the article by Lyu et al published in the recent issue of the World Journal of Gastroenterology(2023;2219-2840).Hepatocellular carcinoma(HCC)is a frequently encountered and highly aggressive primary liver cancer,which remains the third-commonest cause of cancer-related death despite the current therapeutic modalities.There is urgency in developing novel thera-peutic approaches,such as by manipulating extracellular vesicles,which con-stitute a highly heterogeneous nanoparticle population that contains various cargoes.These cargoes have a pivotal role in cell-to-cell communication and can modify the functional level of the recipient cells via their uptake by other recipient cells.Exosomal non-coding RNAs have particular evolving significance in HCC,such as circular RNAs,which have been found differentially expressed in normal hepatic and HCC tissues.The aberrations in their expression levels have a key role in the HCC development and progression and the overall prognosis.In this editorial,we will shed light on the emerging role of exosomal circular RNAs in HCC development and progression,focusing on the oncogenic or potentially tumor suppressive effect of mesenchymal stem cells-derived exosomal non-coding RNAs.

Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

Pressure stimulated current in progressive failure process of combined coal-rock under uniaxial compression:Response and mechanism

Effective monitoring of the structural health of combined coal-rock under complex geological conditions by pressure stimulated currents(PSCs)has great potential for the understanding of dynamic disasters in underground engineering.To reveal the effect of this way,the uniaxial compression experiments with PSC monitoring were conducted on three types of coal-rock combination samples with different strength combinations.The mechanism explanation of PSCs are investigated by resistivity test,atomic force microscopy(AFM)and computed tomography(CT)methods,and a PSC flow model based on progressive failure process is proposed.The influence of strength combinations on PSCs in the progressive failure process are emphasized.The results show the PSC responses between rock part,coal part and the two components are different,which are affected by multi-scale fracture characteristics and electrical properties.As the rock strength decreases,the progressive failure process changes obviously with the influence range of interface constraint effect decreasing,resulting in the different responses of PSC strength and direction in different parts to fracture behaviors.The PSC flow model is initially validated by the relationship between the accumulated charges of different parts.The results are expected to provide a new reference and method for mining design and roadway quality assessment.

A Comparative Study on the Post-Buckling Behavior of Reinforced Thermoplastic Pipes(RTPs)Under External Pressure Considering Progressive Failure

The collapse pressure is a key parameter when RTPs are applied in harsh deep-water environments.To investigate the collapse of RTPs,numerical simulations and hydrostatic pressure tests are conducted.For the numerical simulations,the eigenvalue analysis and Riks analysis are combined,in which the Hashin failure criterion and fracture energy stiffness degradation model are used to simulate the progressive failure of composites,and the“infinite”boundary conditions are applied to eliminate the boundary effects.As for the hydrostatic pressure tests,RTP specimens were placed in a hydrostatic chamber after filled with water.It has been observed that the cross-section of the middle part collapses when it reaches the maximum pressure.The collapse pressure obtained from the numerical simulations agrees well with that in the experiment.Meanwhile,the applicability of NASA SP-8007 formula on the collapse pressure prediction was also discussed.It has a relatively greater difference because of the ignorance of the progressive failure of composites.For the parametric study,it is found that RTPs have much higher first-ply-failure pressure when the winding angles are between 50°and 70°.Besides,the effect of debonding and initial ovality,and the contribution of the liner and coating are also discussed.

Glucocorticoids-based prodrug design:Current strategies and research progress

Attributing to their broad pharmacological effects encompassing anti-inflammation,antitoxin,and immunosuppression,glucocorticoids(GCs)are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus,nephritis,arthritis,ulcerative colitis,asthma,keratitis,macular edema,and leukemia.However,longterm use often causes undesirable side effects,including metabolic disorders-induced Cushing's syndrome(buffalo back,full moon face,hyperglycemia,etc.),osteoporosis,aggravated infection,psychosis,glaucoma,and cataract.These notorious side effects seriously compromise patients'quality of life,especially in patients with chronic diseases.Therefore,glucocorticoid-based advanced drug delivery systems for reducing adverse effects have received extensive attention.Among them,prodrugs have the advantages of low investment,low risk,and high success rate,making them a promising strategy.In this review,we propose the strategies for the design and summarize current research progress of glucocorticoid-based prodrugs in recent decades,including polymer-based prodrugs,dendrimer-based prodrugs,antibody-drug conjugates,peptide-drug conjugates,carbohydrate-based prodrugs,aliphatic acid-based prodrugs and so on.Besides,we also raise issues that need to be focused on during the development of glucocorticoid-based prodrugs.This review is expected to be helpful for the research and development of novel GCs and prodrugs.

Imbalance of Circulating Follicular Regulatory and Follicular Helper T Cell Subpopulations Is Associated with Disease Progression and Serum CYFRA 21-1 Levels in Patients with Non-small Cell Lung Cancer

Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls.Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also analyzed.The correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further explored.Results The TFR/TFH ratio increased significantly in NSCLC patients.The CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage IV.PD-1^(+)ICOS+TFH cells showed a downward trend with increasing stages.Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls.Plasmablasts,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar trends.TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage IV.Conclusion Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.

Risk of progression of Barrett's esophagus in patients with cirrhosis

To study Barrett’s esophagus (BE) in cirrhosis and assess progression to esophageal adenocarcinoma (EAC) compared to non-cirrhotic BE controls.METHODSCirrhotic patients who were found to have endoscopic evidence of BE confirmed by the presence of intestinal metaplasia on histology from 1/1/2000 to 12/1/2015 at Cleveland Clinic were included. Cirrhotic patients were matched 1:4 to BE controls without cirrhosis. Age, gender, race, BE length, hiatal hernia size, Child-Pugh (CP) class and histological findings were recorded. Cases and controls without high-grade dysplasia (HGD)/EAC and who had follow-up endoscopies were studied for incidence of dysplasia/EAC and to assess progression rates. Univariable conditional logistic regression was done to assess differences in baseline characteristics between the two groups.RESULTSA total of 57 patients with cirrhosis and BE were matched with 228 controls (BE without cirrhosis). The prevalence of dysplasia in cirrhosis and controls were similar with 8.8% vs 12% with low grade dysplasia (LGD) and 12.3 % vs 19.7% with HGD or EAC (P = 0.1). In the incidence cohort of 44 patients with median follow-up time of 2.7 years [interquartile range 1.0, 4.8], there were 7 cases of LGD, 2 cases of HGD, and 2 cases of EAC. There were no differences in incidence rates of HGD/EAC in nondysplastic BE between cirrhotic cases and noncirrhotic controls (1.4 vs 1.1 per 100 person- years, P = 0.8). In LGD, cirrhotic patients were found to have higher rates of progression to HGD/EAC compared to control group though this did not reach statistical significance (13.7 vs 8.1 per 100 person- years, P = 0.51). A significant association was found between a higher CP class and neoplastic progression of BE in cirrhotic patients (HR =7.9, 95%CI: 2.0-30.9, P = 0.003).CONCLUSIONCirrhotics with worsening liver function are at increased risk of progression of BE. More frequent endoscopic surveillance might be warranted in such patients.

Numerical analysis of downward progressive landslides in long natural slopes with sensitive clay

Landslides occurring in sensitive clay often result in widespread destruction,posing a significant risk to human lives and property due to the substantial decrease in undrained shear strength during deformation.Assessing the consequences of these landslides is challenging and necessitates robust numerical methods to comprehensively investigate their failure mechanisms.While studies have extensively explored upward progressive landslides in sensitive clays,understanding downward progressive cases remains limited.In this study,we utilised the nodal integration-based particle finite element method(NPFEM)with a nonlinear strain-softening model to analyse downward progressive landslides in sensitive clay on elongated slopes,induced by surcharge loads near the crest.We focused on elucidating the underlying failure mechanisms and evaluating the effects of different soil parameters and strainsoftening characteristics.The simulation results revealed the typical pattern for downward landslides,which typically start with a localised failure in proximity to the surcharge loads,followed by a combination of different types of failure mechanisms,including single flow slides,translational progressive landslides,progressive flow slides,and spread failures.Additionally,inclined shear bands occur within spread failures,often adopting distinctive ploughing patterns characterised by triangular shapes.The sensitive clay thickness at the base,the clay strength gradient,the sensitivity,and the softening rate significantly influence the failure mechanisms and the extent of diffused displacement.Remarkably,some of these effects mirror those observed in upward progressive landslides,underscoring the interconnectedness of these phenomena.This study contributes valuable insights into the complex dynamics of sensitive clay landslides,shedding light on the intricate interplay of factors governing their behaviour and progression.

Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury

BACKGROUND Uridine diphosphate glucuronosyltransferase 1A1(UGT1A1)plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances.However,its contribution to the progression of liver damage remains unclear.AIM To determine the role and mechanism of UGT1A1 in liver damage progression.METHODS We investigated the relationship between UGT1A1 expression and liver injury through clinical research.Additionally,the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model study.RESULTS Patients with UGT1A1 gene mutations showed varying degrees of liver damage,while patients with acute-onchronic liver failure(ACLF)exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic hepatitis.This suggests that low UGT1A1 levels may be associated with the progression of liver damage.In mouse models of liver injury induced by carbon tetrachloride(CCl_(4))and concanavalin A(ConA),the hepatic levels of UGT1A1 protein were found to be increased.In mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression,the hepatic protein levels of UGT1A1 were decreased,which is consistent with the observations in patients with ACLF.UGT1A1 knockout exacerbated CCl_(4)-and ConA-induced liver injury,hepatocyte apoptosis and necroptosis in mice,intensified hepatocyte endoplasmic reticulum(ER)stress and oxidative stress,and disrupted lipid metabolism.CONCLUSION UGT1A1 is upregulated as a compensatory response during liver injury,and interference with this upregulation process may worsen liver injury.UGT1A1 reduces ER stress,oxidative stress,and lipid metabolism disorder,thereby mitigating hepatocyte apoptosis and necroptosis.

Progression from low-grade dysplasia to malignancy in patients with Barrett's esophagus diagnosed by two or more pathologists

AIM To evaluate annual incidence of low grade dysplasia(LGD) progression to high grade dysplasia(HGD) and/or esophageal adenocarcinoma(EAC) when diagnosis was made by two or more expert pathologists.METHODS Studies evaluating the progression of LGD to HGD or EAC were included. The diagnosis of LGD must be made by consensus of two or more expert gastrointestinal pathologists. Articles were searched in Medline, Pubmed, and Embase. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I2 statistic. RESULTS Initial search identified 721 reference articles, of which 53 were selected and reviewed. Twelve studies(n = 971) that met the inclusion criteria were included in this analysis. Among the total original LGD diagnoses in the included studies, only 37.49% reached the consensus LGD diagnosis after review by two or more expert pathologists. Total follow up period was 1532 patient-years. In the pooled consensus LGD patients, the annual incidence rate(AIR) of progression to HGD and or EAC was 10.35%(95%CI: 7.56-13.13) and progression to EAC was 5.18%(95%CI: 3.43-6.92). Among the patients down staged from original LGD diagnosis to No-dysplasia Barrett's esophagus, the AIR of progression to HGD and EAC was 0.65%(95%CI: 0.49-0.80). Among the patients down staged to Indefinite for dysplasia, the AIR of progression to HGD and EAC was 1.42%(95%CI: 1.19-1.65). In patients with consensus HGD diagnosis, the AIR of progression to EAC was 28.63%(95%CI: 13.98-43.27). CONCLUSION When LGD is diagnosed by consensus agreement of two or more expert pathologists, its progression towards malignancy seems to be at least three times the current estimates, however it could be up to 20 times the current estimates. Biopsies of all Barrett's esophagus patients with LGD should be reviewed by two expert gastroenterology pathologists. Follow-up strict surveillance programs should be in place for these patients.