重庆医科大学第二临床学院尼泊尔教案 2008年12月3日 授课题目：Infective endocarditis 授课教师：邓昌明副教授 授课对象：2005级尼泊尔留学生 学时：3学时 目的要求： l、掌握Infective endocarditis的概念、分类、发病因素、发病机理、病理改变、 临床表现及基本防治方法。 2、熟悉Infectiveendocarditis的诊断和治疗原则。 重点：Infectiveendocarditis的鉴别诊断，治疗原则和措施。 难点：Infective endocarditis诊断及处理。 采用教具及电化器材：幼灯片、图片、多媒体投影。 教学内容、方法及时间分配： 首先介绍一典型的Infective endocarditis病例，就此引入本文的正题【多媒体投 影。 Definition(12min) Infective endocarditis(IE)is the condition in which there is microbial infection of the endothelial Surface of the heart.The characteristic lesion,the vegetation,is a variably sized mass of Platelets and fibrin in which abundant microorganisms and a little inflammatory cells are enmeshed.Heart valves are most commonly involved however,infection may occur at the site of a septal defect or on chordae tendineae or mural endocard-ium.Many diverse species of bacteria,fungi,mycobacteria, rickettsiae,chlamydiae,and myoplasma Cause IE:nevertheless,Streptococci, and fastidious gram that reside in the oral cavity and upper respiratorytract cause the majority of cause of IE has traditionally been classified as acute or subacute,the acute IE has marked systemic toxicity and is dead in days to less than 6 weeks.the latter is a case of an indolent.less toxic illness resulting in death in 6 weeks to 6 months or more.Toda marked xi and eral weekso weeks to months with only modest toxicity and rarely causes metastatic infection. Acute IE is caused by staphylococcus aureus,whereas the subacute syndrome is more likely caused by viridans streptococci,enterococci,coagulase-negative staphylococci, was 4.2 per 100.000 patient-years from 1970 to 1987.during the 1980's.the yearly incidence of IE per 100.000 population ranged from 1.7 to 2.0.Endocarditis occurred more frequently in men. valve prolapse,degenerative heart disease asymmetrical septal hypertrophy.or intravenous drug abuse.but predisposing conditions cannot be identified in 25 to 45
重庆医科大学第二临床学院尼泊尔教案 2008 年 12 月 3 日 授课题目：Infective endocarditis 授课教师：邓昌明副教授 授课对象：2005 级尼泊尔留学生 学时：3 学时 目的要求： 1、掌握 Infective endocarditis 的概念、分类、发病因素、发病机理、病理改变、 临床表现及基本防治方法。 2、熟悉 Infective endocarditis 的诊断和治疗原则。 重点：Infective endocarditis 的鉴别诊断，治疗原则和措施。 难点：Infective endocarditis 诊断及处理。 采用教具及电化器材：幼灯片、图片、多媒体投影。 教学内容、方法及时间分配： 首先介绍一典型的 Infective endocarditis 病例，就此引入本文的正题【多媒体投 影】。 Definition(12min) Infective endocarditis (IE) is the condition in which there is microbial infection of the endothelial Surface of the heart. The characteristic lesion, the vegetation, is a variably sized mass of Platelets and fibrin in which abundant microorganisms and a little inflammatory cells are enmeshed. Heart valves are most commonly involved; however, infection may occur at the site of a septal defect or on chordae tendineae or mural endocard-ium. Many diverse species of bacteria, fungi, mycobacteria, rickettsiae, chlamydiae, and myoplasma Cause IE; nevertheless, Streptococci, staphylococci, enterococci, and fastidious gram-negative coccobacilli that reside in the oral cavity and upper respiratory tract cause the majority of cause of IE. IE has traditionally been classified as acute or subacute, the acute IE has marked systemic toxicity and is dead in days to less than 6 weeks, the latter is a case of an indolent, less toxic illness resulting in death in 6 weeks to 6 months or more. Today acute IE presents with marked toxicity and progresses over days to several weeks to valvular destruction and metastatic infection. In contrast, subacute IE evolves over weeks to months with only modest toxicity and rarely causes metastatic infection. Acute IE is caused by staphylococcus aureus, whereas the subacute syndrome is more likely caused by viridans streptococci, enterococci, coagulase-negative staphylococci, or gram-negative coccobacilli. Epidemiology(15min) The incidence of IE is remarkably similar in developed Countries. the incidence of IE was 4.2 per 100,000 patient-years from 1970 to 1987. during the 1980’s, the yearly incidence of IE per 100,000 population ranged from 1.7 to 2.0. Endocarditis occurred more frequently in men. From 55 to 75 per cent of patients with native valve endocarditis (NVE) have predisposing conditions: rheumatic heart disease, congenital heart disease, mitral valve prolapse, degenerative heart disease asymmetrical septal hypertrophy, or intravenous drug abuse. but predisposing conditions cannot be identified in 25 to 45
per cent of patients.The namre of predisposing conditions and in par.the microbiology of correlate with the age of patients Clinical classification(12min) Cases of IE occurring in defined populations or settings often share clinical features and microbiology. Children The i cidence of IE among hospitalized children ranges from Iin4500 toI in2800 IE has been noted in neonates.with increasing frequency among neonates.IE is associated with very high mortality rates. Adults some of the common features and evolving aspects of IE occurring in adults have been noted in considering the epidemiology of IE.Mitral valve prolapse has emerged as a predominant p edisn sing for 7o30 per cent of NVE no abuse o in case-control studies,the relative risk of endocarditis among patients with mitral valve prolapse range from 3.5 to 8.2.Risk is also increased among men and patients over age 45.The mortality rate was 14 per cent.similar to rates noted in nie in general Rheumatic heart dis s the cent of cases in the1970 ing cardiac lesion for IE in 20 to 25 per endocarditis occurs most frequently on the mitral valve.the aortic valve is the next most common site for lE. Congenital heart disease is the substrate for IE in 10 to 20 per cent of younger adults and per cent of oder adults the common predisposing lesions are ventricular septal defects and biscuspid aortic va Intravenous drug abusers The risk for IE among intravenous drug abusers,2 to 5 per cent per patient-year,is estimated to be severalfold greater than that of patients with rheumatic heart disease or prosthetic valves.Endocarditis occurring in intravenous drug abusers has a unique property to infect right heart valves. ntra abus is a risk factorfo nt NVE. Prosthetic valve endocarditis(PVE)Epidemiologic stdies suggest that PVp comprises 10 to 20 per cent ofall cases of IE in developed countries.PVE has been called“earb”when symptoms begin within60 days of valve surgery and“late”wih onset thereafter patients with antecedent native valve endocarditis.particularly if active,are at increased risk for PVE. Etiological Microoganisms(5min) Viridans streptococci.These streptococci,which cause 30 to 65 per cent of NVE unrelated to drug abuse Streptococcus bovis and other streptococci s.bovis.part of the gastrointestinal tract noma fora causes 2.per cent of the episodes of streptococ.CoupA streptococci.which can infe vahves,caus Streptococcus pneumoniae.Although pneumococcal bacteremia occurs frequently,S. pneumoniae accounts for I to 3 per cent of NVE cases. Staphylococci S.aureus is main cause of acute IE,but S.bovis is major cause of subacute IE
per cent of patients. The nature of predisposing conditions and in part, the microbiology of IE correlate with the age of patients. Clinical classification(12min) Cases of IE occurring in defined populations or settings often share clinical features and microbiology. Children The incidence of IE among hospitalized children ranges from 1 in 4500 to 1 in 2800. Recently. IE has been noted in neonates. with increasing frequency among neonates. IE is associated with very high mortality rates. Adults some of the common features and evolving aspects of IE occurring in adults have been noted in considering the epidemiology of IE. Mitral valve prolapse has emerged as a predominant predisposing structural cardiac abnormality and accounts for 7 to 30 per cent of NVE in adults which is not related to drug abuse or nosocomial infection. in case-control studies, the relative risk of endocarditis among patients with mitral valve prolapse range from 3.5 to 8.2. Risk is also increased among men and patients over age 45. The mortality rate was 14 per cent, similar to rates noted in NVE in general. Rheumatic heart disease was the predisposing cardiac lesion for IE in 20 to 25 per cent of cases in the 1970’s and 1980’s. In patients with rheumatic heart disease, endocarditis occurs most frequently on the mitral valve, the aortic valve is the next most common site for IE. Congenital heart disease is the substrate for IE in 10 to 20 per cent of younger adults and 8 per cent of older adults the common predisposing lesions are ventricular septal defects and biscuspid aortic valves. Intravenous drug abusers The risk for IE among intravenous drug abusers, 2 to 5 per cent per patient-year, is estimated to be severalfold greater than that of patients with rheumatic heart disease or prosthetic valves. Endocarditis occurring in intravenous drug abusers has a unique property to infect right heart valves, intrarenous drug abuse is a risk factor for recurrent NVE. Prosthetic valve endocarditis(PVE) Epidemiologic studies suggest that PVE comprises 10 to 20 per cent of all cases of IE in developed countries. PVE has been called “early” when symptoms begin within 60 days of valve surgery and “late” with onset thereafter, patients with antecedent native valve endocarditis, particularly if active, are at increased risk for PVE. Etiological Microoganisms(5min) Viridans streptococci. These streptococci, which cause 30 to 65 per cent of NVE unrelated to drug abuse. Streptococcus bovis and other streptococci S. bovis, part of the gastrointestinal tract normal flora, causes 27 per cent of the episodes of streptococcal NVE. Group A streptococci, which can infect normal valves, cause rare episodes of endocarditis. Streptococcus pneumoniae. Although pneumococcal bacteremia occurs frequently, S. pneumoniae accounts for 1 to 3 per cent of NVE cases. Staphylococci S. aureus is main cause of acute IE, but S. bovis is major cause of subacute IE
Funci candida albicans and non-albicans candida species are the most common of the many funga PATHOGENESIS(15min) The pathogenesis of IE is not filly elucidated.The interactions between the human host and selected microorganisms that culminate in IE involve the vascular endothelium.hemostatic mechanisms.the host immune system.gross anatomic abnor ities in the heart,surfa properties of microorganisms.and peripherd events that initiate bacteremia.Each component of these interactions is in itself complex.infhenced by many factors,it is hypothesized that platelet-fibrin deposition occurs spontaneously in persons vulnerable to endocarditis and that these deposits, called nonbacterial thrombotic endocarditis (NBTE)are the sites at which organisms adhere to initiate IE. nbacteria l thro nbotic endocardi Two major mechanisms are very important in the formation of NBTE,endothelial injury and a hypercoagulable state.NBTE has been found in 1.3 per cent of patients at autopsy and,while present at all ages,is more common with increasing age.The sites of these NBTE correspond closely with the location of infected vegetations in patients withIE. Three hemodynamic circumstances may injure th initiating NBTE:(1) high-velocity jet impacting endothelium;(2)flow from a high-to a low-pressure chamber;(3)flow across a narrow orifice at high velocity.The flow through a narrowed orifice deposited bacteria maximally at the low-pressure sink immediately beyond an orifice or at the site where a jet stream impacts a surface.These are the same sites whe h】 hemo lances. Conversion of NBTE to IE The initiating event that utimately converts NBTE to IE is the entry of microorganisms into the circulation as a consequence of localized infection or trauma to a body surface.The frequency and magnitude of bacteremia associated with dail activities and health care procedures appear related to specific mucosa sufaces and skm.the ing bacteria. the dis ease state of the suface.and the extent of the local traume Bacteremia rate are highest fo that traumatize the oral mucosa,particularly the gingiva,and progressively decrease with procedtues involving the genitourinary tract and the gastrointestinal tract Although IE develops when circulating microorganisms are deposited at a site of NBTE.the coincidence of bacteremia cause IE the and NBTE does not uiformly result in IE.To ust be able to persist mu nd propagate m This requires resistance tohost defenses After adherence to the NBTE or endothelium (in the case of virulent organisms) Persistence and multiplication result in a complex dynamic process during which the infected vegetation increases in size by platelet-fibrin aggregation.microorganisms are shed into the blood,and vegetation fragm ents lize.Staphyloc nccmd promote and growth of the vegetation The vegetation has been considered a sheltered site wherein bacteria were protected from polymorphonuclear leukocytes PATHOPHYSIOLOGY(12min) Aside from the constitutional symptoms of infection,which are likely mediated by
Funci candida albicans and non-albicans candida species are the most common of the many fungal organisms identified as causing IE. PATHOGENESIS(15min) The pathogenesis of IE is not fully elucidated. The interactions between the human host and selected microorganisms that culminate in IE involve the vascular endothelium, hemostatic mechanisms, the host immune system, gross anatomic abnormalities in the heart, surface properties of microorganisms, and peripheral events that initiate bacteremia. Each component of these interactions is in itself complex, influenced by many factors, it is hypothesized that platelet-fibrin deposition occurs spontaneously in persons vulnerable to endocarditis and that these deposits, called nonbacterial thrombotic endocarditis (NBTE), are the sites at which microorganisms adhere to initiate IE. Development of nonbacterial thrombotic endocarditis Two major mechanisms are very important in the formation of NBTE, endothelial injury and a hypercoagulable state. NBTE has been found in 1.3 per cent of patients at autopsy and, while present at all ages, is more common with increasing age. The sites of these NBTE correspond closely with the location of infected vegetations in patients with IE. Three hemodynamic circumstances may injure the endothelium, initiating NBTE: (1) a high-velocity jet impacting endothelium; (2) flow from a high-to a low-pressure chamber; (3) flow across a narrow orifice at high velocity. The flow through a narrowed orifice deposited bacteria maximally at the low-pressure sink immediately beyond an orifice or at the site where a jet stream impacts a surface. These are the same sites where NBTE forms as a result of hemodynamic circumstances. Conversion of NBTE to IE The initiating event that ultimately converts NBTE to IE is the entry of microorganisms into the circulation as a consequence of localized infection or trauma to a body surface. The frequency and magnitude of bacteremia associated with daily activities and health care procedures appear related to specific mucosal surfaces and skin, the density of colonizing bacteria, the disease state of the surface, and the extent of the local trauma. Bacteremia rates are highest for events that traumatize the oral mucosa, particularly the gingiva, and progressively decrease with procedures involving the genitourinary tract and the gastrointestinal tract. Although IE develops when circulating microorganisms are deposited at a site of NBTE, the coincidence of bacteremia and NBTE does not uniformly result in IE. To cause IE the organism must be able to persist and propagate on the endothelium. This requires resistance to host defenses. After adherence to the NBTE or endothelium (in the case of virulent organisms). Persistence and multiplication result in a complex dynamic process during which the infected vegetation increases in size by platelet-fibrin aggregation, microorganisms are shed into the blood, and vegetation fragments embolize. Staphylococci and streptococci promote platelet aggregation and growth of the vegetation. The vegetation has been considered a sheltered site wherein bacteria were protected from polymorphonuclear leukocytes. PATHOPHYSIOLOGY(12min) Aside from the constitutional symptoms of infection, which are likely mediated by
cvtokines the clinical manifestations of ie result from (1)the local destructive effects of intracardiac infe tion;(2)the emboliza tion of bland oi sep fragments vegetations to distant sites,resulting in infarction or infection:(3)the hematogenou seeding of remote sites during continous bacteremia;and(4)an antibody response to the infecting organism with subsequent tissue injury due to deposition of preformed immune complexes or antibody-complement interaction with antigens deposited in tissues The intr cardiac consequences of IE range from an attendant tissue damage catastrophic,when infection is locally destructive or extends beyond the valve leaflet. Distortion of valve leaflets,rupture of chordae tendineae,and performations or fistulas between major vessels and cardiac chambers or between chambers themselves as a consequence of burrowing infection may result in progressive congestive heart Infection,particularly that involving the aortic valve or prosthetic valves,may extend into paravalvular tissue and result in abscesses and persistent fever,disruption of the conduction system with electro cardiographic conduction abnormalities and relevant arhythmias,or purulent pericarditis.Large vegetations,particularly at the mitral can onal valvular stenos and her ynami dent in I 1 to 43 per cent ofpatients The persistent bacteremia of IE.with or without septic emboli.may result in metastatic infection.In general,these infections originate before initiation of antimicrobial therapy:however:clinical manifestation may be delayed.These infections may pre t as local sig and s ymp toms or as sistent fever during therapy:Any organ or tissue may be infected,including the e spleen,kidney,brair meninges,pericardium,bone,synovium,and even vitreous humor Metastati abscesses are often small and miliary.And the humoral and cell-mediated arms of the immune system are stimulated in patient with IE. CLINICAL FEATURES min) The interval be we en the med initiating bacteremiand of symptomsof E is short.It is estimated that more than 80 per cent of patients with NVE develop symptoms within 2 weeks.Interestingly,in some patients with intraoperative or perioperative infection of prosthetic valves.the incubation period may be prolonged to 5 or more months) Fever is the most com on symptom and sign in patients with IE.In patients with subacute IE not associated with rigors.Fever may be absent or minimal in the elderly or in those with congestive heart failure,severe debility.or chronic renal failure and occasionally in patients with nie caused by coagulase-negative staphylococci. Heart murmurs are noted in 80 to 85 per cent of patients with NVE and are emblematic of the les on pre to IE.Murmu only not audible i patients with tricuspid valve IE.Similarly,in acute NVE due to S.aureus,murmurs are heard in only 30 to 45 per cent of patients on initial evaluation but are ultimately noted in 75 to 85 per cent.The new or changing murmurs are relatively in-frequent in subacute NVE and are more prevelent in acute IE and PVE.They are frequently
cytokines, the clinical manifestations of IE result from (1) the local destructive effects of intracardiac infection; (2) the embolization of bland or septic fragments of vegetations to distant sites, resulting in infarction or infection; (3) the hematogenous seeding of remote sites during continous bacteremia; and (4) an antibody response to the infecting organism with subsequent tissue injury due to deposition of preformed immune complexes or antibody-complement interaction with antigens deposited in tissues. The intracardiac consequences of IE range from an attendant tissue damage to catastrophic, when infection is locally destructive or extends beyond the valve leaflet, Distortion of valve leaflets, rupture of chordae tendineae, and performations or fistulas between major vessels and cardiac chambers or between chambers themselves as a consequence of burrowing infection may result in progressive congestive heart failure. Infection, particularly that involving the aortic valve or prosthetic valves, may extend into paravalvular tissue and result in abscesses and persistent fever, disruption of the conduction system with electro cardiographic conduction abnormalities and relevant arrhythmias, or purulent pericarditis. Large vegetations, particularly at the mitral valve, can result in functional valvular stenosis and hemodynamic deterioration. Embolization of fragments from vegetations is evident in 11 to 43 per cent of patients. The persistent bacteremia of IE, with or without septic emboli, may result in metastatic infection. In general, these infections originate before initiation of antimicrobial therapy; however, clinical manifestation may be delayed. These infections may present as local signs and symptoms or as persistent fever during therapy. Any organ or tissue may be infected, including the spleen, kidney, brain, meninges, pericardium, bone, synovium, and even vitreous humor. Metastatic abscesses are often small and miliary. And the humoral and cell-mediated arms of the immune system are stimulated in patient with IE. CLINICAL FEATURES(9min) The interval between the presumed initiating bacteremia and the onset of symptoms of IE is short. It is estimated that more than 80 per cent of patients with NVE develop symptoms within 2 weeks. Interestingly, in some patients with intraoperative or perioperative infection of prosthetic valves, the incubation period may be prolonged (2 to 5 or more months). Fever is the most common symptom and sign in patients with IE. In patients with subacute IE, fevers are low grade, rarely exceeding 39.4℃， remittent, and usually not associated with rigors. Fever may be absent or minimal in the elderly or in those with congestive heart failure, severe debility, or chronic renal failure and occasionally in patients with NVE caused by coagulase-negative staphylococci. Heart murmurs are noted in 80 to 85 per cent of patients with NVE and are emblematic of the lesion predisposing to IE. Murmurs are commonly not audible in patients with tricuspid valve IE. Similarly, in acute NVE due to S. aureus, murmurs are heard in only 30 to 45 per cent of patients on initial evaluation but are ultimately noted in 75 to 85 per cent. The new or changing murmurs are relatively in-frequent in subacute NVE and are more prevelent in acute IE and PVE. They are frequently
important harbingers of congestive hear failre Enlargement of spleen is noted less commonly in recent reports than previously.and it is more common in subacute IE of long duration. Although 50 per cent of patients with IE were reported to have one or more of the classic peripheral manifestations of this illess,these findings are encountered less frequently today. Petechiae the most common of these manifestations.are found on the palpebra conjunctiva.the buccal and palatal mucosa,and the extremities Splinter of subungual hemorrhages are the dark red.linear or occasionally flame-shaped streaks in the nail bed of the fingers or toes. Osler's nodes are small.tender subcutaneous nodules that develop in the pulp of the digits or occasionally more proximally in the fingers and persist for hours to several days Roth spots,oval retinal hemorrhages with pale centers.are infrequent findings in patients with Ie. Janeway lesions are small erythematous or hemorrhagic macular nontender lesions on the palms and soles and are the consequence of septic embolic events. Musculoskeletal symptoms are common patienth IE.these inclucle arthralgias and myalgias Systemic emboli are among the most common clinical sequence of IE.occurring in up to 40 per cent of patients,and are frequent subclinical events found only at autopsy Emboli ofien antedate diagnosis.the incidence of embolic events decreases promptly administration Neursal smptoms and simns 30 n more frequent when IE is caused by S.anreus.and are associated with increased mortality rates.Neurological manifestation,such as a stroke.intracelebral hemorrage. or subarachnoid hemorrage.Severe headche seizure and encephalopathy Congestive heart failur nocrnptRPebea (CHE) ing IF is primarily the result of chordae Renal insufficiency as a result of immune complex-mediated glomerulonephritis occurs in less than 15 per cent of patients with IE focal glomerulonephritis and renal infarcts cause hematuria DIAGNOSISO5min) sym and sigr of endocarditisare ofe ofen resul from a complication of IE rather than rfect the intracardiac infectio itself.Consequentl.if physicians are to avoid overlooking the diagnosis of lE.a high index of suspicion must be investigated when patients with fever present with one or more of the cardinal elements of IE:a predisposing cardiac lesion or behavior pattern mbolic pheno and evidan active IE must be considered in a patient with significant valvular heart disease and persistent unexplained fever,in the intravenous drug abuser with fever especially if there is cough and pleuritic chest pain,or in the young patient with an unexpected stroke or subarachnoid hemorrhage.The development of a new regurgitant murmur must raise the possibility ofIE
important harbingers of congestive heart failure. Enlargement of spleen is noted less commonly in recent reports than previously, and it is more common in subacute IE of long duration. Although 50 per cent of patients with IE were reported to have one or more of the classic peripheral manifestations of this illess, these findings are encountered less frequently today. Petechiae the most common of these manifestations, are found on the palpebral conjunctiva, the buccal and palatal mucosa, and the extremities. Splinter of subungual hemorrhages are the dark red, linear or occasionally flame-shaped streaks in the nail bed of the fingers or toes. Osler’s nodes are small, tender subcutaneous nodules that develop in the pulp of the digits or occasionally more proximally in the fingers and persist for hours to several days. Roth spots, oval retinal hemorrhages with pale centers, are infrequent findings in patients with IE. Janeway lesions are small erythematous or hemorrhagic macular nontender lesions on the palms and soles and are the consequence of septic embolic events. Musculoskeletal symptoms are relatively common in patient with IE, these inclucle arthralgias and myalgias. Systemic emboli are among the most common clinical sequence of IE, occurring in up to 40 per cent of patients, and are frequent subclinical events found only at autopsy. Emboli often antedate diagnosis, the incidence of embolic events decreases promptly during the administration of effective antibiotic therapy. Neurological symptoms and signs occur in 30 to 40 per cent of patients with IE, are more frequent when IE is caused by S. anreus, and are associated with increased mortality rates. Neurological manifestation, such as a stroke, intracelebral hemorrage, or subarachnoid hemorrage. Severe headche seizure and encephalopathy. Congestive heart failure (CHF) complicating IE is primarily the result of valve destruction or distortion or rupture of chordae tendineae. Renal insufficiency as a result of immune complex-mediated glomerulonephritis occurs in less than 15 per cent of patients with IE focal glomerulonephritis and renal infarcts cause hematuria. DIAGNOSIS(15min) The symptoms and signs of endocarditis are often constitutional and when localized, often result from a complication of IE rather than reflect the intracardiac infection itself. Consequently, if physicians are to avoid overlooking the diagnosis of IE, a high index of suspicion must be investigated when patients with fever present with one or more of the cardinal elements of IE: a predisposing cardiac lesion or behavior pattern, bacteremia, embolic phenomenon, and evidence of an active endocardial process. IE must be considered in a patient with significant valvular heart disease and a persistent unexplained fever, in the intravenous drug abuser with fever especially if there is cough and pleuritic chest pain, or in the young patient with an unexpected stroke or subarachnoid hemorrhage. The development of a new regurgitant murmur must raise the possibility of IE