Tuberculosis in HIV-infected children in Europe, Thailand and Brazil: Paediatric TB-HIV EuroCoord study

SETTING: Centres participating in the Paediatric European Network for Treatment of AIDS (PENTA), including Thailand and Brazil. OBJECTIVE: To describe the incidence, presentation, treatment and treatment outcomes of tuberculosis (TB) in human immunodeficiency virus (HIV) infected children. DESIGN: Observational study of TB diagnosed in HIV-infected children in 2011-2013. RESULTS: Of 4265 children aged <16 years, 127 (3%) were diagnosed with TB: 6 (5%) in Western Europe, 80 (63%) in Eastern Europe, 27 (21%) in Thailand and 14 (11%) in Brazil, with estimated TB incidence rates of respectively 239, 982, 1633 and 2551 per 100 000 person-years (py). The majority (94%) had acquired HIV perinatally. The median age at TB diagnosis was 6.8 years (interquartile range 3.0-11.5). Over half (52%) had advanced/severe World Health Organization stage immunodeficiency; 67 (53%) were not on antiretroviral therapy (ART) at TB diagnosis. Preventive anti-tuberculosis treatment was given to 23% (n = 23) of 102 children diagnosed with HIV before TB. Eleven children had unfavourable TB outcomes: 4 died, 5 did not complete treatment, 1 had recurrent TB and 1 had an unknown outcome. In univariable analysis, previous diagnosis of acquired immune-deficiency syndrome, not being virologically suppressed on ART at TB diagnosis and region (Brazil) were significantly associated with unfavourable TB outcomes. CONCLUSION: Most TB cases were from countries with high TB prevalence. The majority (91%) had favourable outcomes. Universal ART and TB prophylaxis may reduce missed opportunities for TB prevention

Tuberculosis in HIV-infected children in Europe, Thailand and Brazil: paediatric TB-HIV EuroCoord study.

SETTING: Centres participating in the Paediatric European Network for Treatment of AIDS (PENTA), including Thailand and Brazil. OBJECTIVE: To describe the incidence, presentation, treatment and treatment outcomes of tuberculosis (TB) in human immunodeficiency virus (HIV) infected children. DESIGN: Observational study of TB diagnosed in HIV-infected children in 2011-2013. RESULTS: Of 4265 children aged <16 years, 127 (3%) were diagnosed with TB: 6 (5%) in Western Europe, 80 (63%) in Eastern Europe, 27 (21%) in Thailand and 14 (11%) in Brazil, with estimated TB incidence rates of respectively 239, 982, 1633 and 2551 per 100 000 person-years (py). The majority (94%) had acquired HIV perinatally. The median age at TB diagnosis was 6.8 years (interquartile range 3.0-11.5). Over half (52%) had advanced/severe World Health Organization stage immunodeficiency; 67 (53%) were not on antiretroviral therapy (ART) at TB diagnosis. Preventive anti-tuberculosis treatment was given to 23% (n = 23) of 102 children diagnosed with HIV before TB. Eleven children had unfavourable TB outcomes: 4 died, 5 did not complete treatment, 1 had recurrent TB and 1 had an unknown outcome. In univariable analysis, previous diagnosis of acquired immune-deficiency syndrome, not being virologically suppressed on ART at TB diagnosis and region (Brazil) were significantly associated with unfavourable TB outcomes. CONCLUSION: Most TB cases were from countries with high TB prevalence. The majority (91%) had favourable outcomes. Universal ART and TB prophylaxis may reduce missed opportunities for TB prevention.

Coronarographic and pathomorphological characteristics of unstable atherosclerotic plaques in acute coronary syndromes.

The proximal segments of the main coronary vessels are the most often localization of "soft" unstable atherosclerotic plaques. The maximum number of plaques developed in the anterior descending branch of the left coronary artery. Pathognomonic relationship was found between the type of these plaques (with ulceration, rupture, thrombosis) and certain acute coronary syndrome. It was shown that the criteria of the plaque instability correlated with clinical manifestations of coronary syndromes. The bases and effects of "pathological" vascularization of unstable atherosclerotic plaques on the angioarchitectonics and hemodynamics of the heart were determined. Dissociation between myocardial vascularization degree and myocardial blood supply index was detected, which underlies the development of "unstable" myocardium in patients with acute coronary syndromes.

Pathomorphology of variant relationships between left ventricle and interventricular septum in hypertensive heart.

We carried out complex pathomorphological analysis of hearts (n=640) with pronounced left ventricular hypertrophy accompanied by asymmetric hypertrophy of interventricular septum, which were isolated from patients died of hypertension. The most frequent variants of pathomorphological interrelationships between the left ventricle and interventricular septum in hypertensive hearts were septoconcentric, posteroseptal, and anteroseptal relations. The study revealed alterations in the left ventricle (the state of ventricular cavity, its volume, and structural remodeling) characteristic of each variants and underlying the pathognomonic manifestations in cardio- and hemodynamics. The role of coronary and myocardial factors in the development and progression of myocardial hypertrophy was established.

Morphogenesis and variants of remodeling of atherosclerotic heart.

Morphogenesis of atherosclerotic heart is presented on the basis of complex pathomorphological analysis of 1000 autopsies. Special attention was paid to the dilatation and hypertrophic variants and to structural mechanisms of heart and coronary vessel remodeling under conditions of atherosclerotic process. Predominant remodeling of atherosclerotic heart and coronary arteries by the dilatation variant determines unfavorable prognosis of heart failure. Compensatory and adaptive processes (cardiomyocyte hypertrophy and collateral circulation) developing in the heart compensate for functional insufficiency of the organ for some time.

Pathomorphology of atherosclerotic coronary artery aneurysms and heart architectonics.

We evaluated pathognomonic incidence of atherosclerotic aneurysms in the anterior interventricular branch of the left coronary artery and proved greatest vulnerability of its first proximal segments. Positive correlations between the incidence of aneurysms in major coronary arteries and their size and bag-like shape were revealed. The characteristic aneurysm-dependent alterations of cardiac angioarchitectonics were found, which underlie pronounced shifts in coronary hemodynamics. Certain criteria for coronarographic diagnostics of atherosclerotic aneurysms were proposed with the methods of there correction. A thanatologic relation of coronary artery aneurysms to the nature of fatal complications is substantiated.

Pathomorphology of postinfarction myocardial ischemia during atherosclerotic obstruction of coronary arteries.

Pathomorphological criteria of early postinfarction angina included segmentary atherosclerotic obstruction of the upper segments of the coronary artery supplying the infarction area, recurrent acute myocardial infarction, maximum decrease in vascularization of the left posterior ventricular wall; and individual changes in angioarchitectonics of the heart promoting hibernation of the myocardium. Pathognomonic morphological criteria of silent postinfarction myocardial ischemia included diffuse extensive atherosclerotic obstruction of lower segments in the coronary artery supplying the infarction area and total hypervascularization of the myocardium, first acute myocardial infarction of the left ventricular anterior wall, and maximum decrease in vascularization of the anterior and posterior wall in the left ventricle. These coronary-myocardial relationships contribute to stunning of the myocardium. Zones of hypokinesia and akinesia were revealed in the left ventricle, which reflects the phenomenon of resting myocardium associated with isolation of heart angioarchitectonics.

Variants of cardiomyopathic heart pathomorphogenesis. comparison of echocardiographic and endomyocardial biopsy findings.

The main variants of cardiomyopathies (undifferentiated, dilatational, hypertrophic, and restrictive) were distinguished using a complex pathomorphological analysis of 600 cardiomyopathic hearts detected in 5000 autopsies after cardiovascular death. The main pathomorphological diagnostic criteria for each variant were defined. High diagnostic value of lifetime echocardiographic diagnosis in comparison with myocardial biopsy was shown. The informative value of endomyocardial biopsy in cardiomyopathic heart is higher, if the method is combined with clinical examinations, noninvasive and invasive studies.

Pathomorphology and pathogenic role of myocardial bridges in sudden cardiac death.

Pathognomonic incidence of myocardial bridges during obstructive hypertrophic cardiomyopathy, hypertension, and ischemic heart disease was established. Myocardial bridges were predominantly found in the median segments of major coronary arteries with prevailence of bridge-like obstructions in the anterior interventricular branch of the left coronary artery. Typical changes in cardiac angioarchitectonics indicating pronounced inadequacy of coronary blood flow were determined depending on the segmentary directionality of bridge obstruction. The data attest to pronounced pathogenetic role of myocardial bridges in sudden cardiac death.

Pathomorphological criteria for cardiosclerosis and angioarchitectonics of the hypertrophic myocardium in hypertensive heart.

We performed a pathomorphological study of 200 hearts with cicatricial changes from patients died from hypertensive disease. Most postinfarction scars in men were transmural and localized in the anterior and posterior wall of the left ventricle and in the interventricular septum. Non-transmural scars were revealed in the lateral wall (primarily in women). Pathognomonic changes in the architectonics of the heart included reduction of regional blood flow and segmentary, discontinuously extended, and diffusely extended atherosclerotic obstruction. Changes in the index of blood supply to the myocardium corresponded to pronounced decrease in vascularization of the hypertrophic left ventricle. A correlation was found between the index of blood supply to the myocardium and mean systolic and diastolic blood pressure. Therefore, the coronary bed did not satisfy the demands of hypertensive heart with cicatricial changes.

Pathomorphological variants of midventricular obstruction of interventricular septum during hypertrophic cardiomyopathy.

Postmortem contrast cardiac ventriculography, coronarography, volume-mass and planimetric cardiometry, as well as echocardiography and pathomorphological data correlation technique were employed for examination of the hearts from patients died from hypertrophy cardiomyopathy (n=100). The following variants of midventricular hypertrophy of the interventricular septum (midventricular obstruction) were established: midleft ventricular, midright ventricular, midproximal, midmaximal. Isolated distal apex hypertrophy and apical hypertrophy were also documented. These variants and forms of cardiac pathology are determined by peculiar changes in geometrical structure of the septum and left ventricle. Multiplanar variability and mobility of interventricular septum combined with peculiar catenary shape promote specific abnormalities of intracardiac hemodynamics determining dissociation between the echocardiographic and pathomorphological diagnostic data and underlying the leading elements of patho- and thanatogenesis of hypertrophic cardiomyopathy.

Pathomorphology of vascular bed in different variants of arrhythmogenic heart development.

A total of 200 hearts from patients with various forms of cardiosclerosis and pronounced disorders of the heart rhythm were examined postmortem by contrast polypositional cardioventriculography, coronarography, volume and weight cardiometry, and morphometry. Left-ventricular, right-ventricular, and septal variants of arrhythmogenic heart development were distinguished. Left-ventricular variant is characterized by compensatory restructuring of the vascular bed with appreciably increased volume of vascular density mainly in the left ventricle and with the median left type of blood supply. The right-ventricular variant is characterized by signs of compensation and decompensation of circulation and intensification of the right ventricular vascularization. The septal variant is characterized by signs of vascular bed decompensation with more intense vascularization of the septum. The detected diagnostic criteria indicate appreciable structural rearrangement of the coronary bed of arrhythmogenic heart, which explains the essential shifts in stimulation, contraction, and mechanical characteristics of the heart ventricles.

Postinfarction remodeling of the heart: types of pathomorphological changes in the right ventricle.

New geometric characteristics of the right ventricle depended on the localization of macrofocal transmural scars in the left ventricle of postinfarction heart. Most pronounced changes in the right ventricle were observed during dilatational and hypertrophic remodeling of the heart. The increase and decrease in the volume were most frequently occurring and pathognomonic forms of pathomorphological changes in the right ventricle. Dilatational remodeling was accompanied by a decrease in the volume of the right ventricle. The increase in the volume of this ventricle was typical of hypertrophic remodeling. Pathological variability in the right ventricle underlies the development of severe disturbances in intracardiac hemodynamics, i.e., patho- and thanatogenesis of postinfarction heart.

Pathomorphological criteria of arrhythmogenic heart.

Pathomorphological criteria of arrhythmogenic heart include structural compartmentalization with primary changes in the right ventricle and interventricular septum, fibro- and lipomatosis of the myocardium, and disseminated coronary obstruction. Ischemic focuses in the conducting system are the site of formation of arrhythmogenic substance promoting the development and progression of cardiac arrhythmias. Cardioneuropathy and pathological motility of the interventricular septum lead to systolic dysfunction and contribute to asynchronous excitation and contraction of ventricles in arrhythmogenic heart.

Pathomorphology of the vascular bed of postinfarction heart in various types of remodeling.

We evaluated pathomorphological changes in the vascular bed of postinfarction heart in various types of remodeling. Dilatational remodeling was characterized by dilation of coronary arteries, increase in their volume density, and regular arrangement. Signs of coronary blood flow reduction and microcirculatory disturbances in the left ventricle were revealed during hypertrophic remodeling. Aneurysmal remodeling was characterized by the presence of small-vascular collateral-anastomotic plexus and reduction of the microcirculatory bed. Endocardial remodeling was accompanied by hypervascularization of the myocardium, formation of new coronary vessels, and reduced capillarization in the left ventricle of postinfarction heart.

Pathomorphological characteristics of cardiac remodeling after myocardial infarction.

Dilatational, hypertrophic, aneurysmal, and endocardial variants of remodeling were revealed in the postinfarction heart. The most prevalent dilatational remodeling is characterized by uniform or nonuniform elongation of ventricular cavities and increase in ventricular volume. Characteristic features of the hypertrophic type are hypertrophied interventricular septa and left ventricular wall and reduced or unchanged left ventricular volume. Pronounced changes in the configuration of the left ventricle due to the formation of single or multiple aneurysms were typical of aneurysmal remodeling. Endocardial remodeling was characterized by cicatricial changes and smoothed relief of the parietal endocardium. These variants and forms of remodeling determine disturbances in intracardial hemodynamic and thanatogenesis in the postinfarction period.

Pathomorphological manifestations of antiocclusive factor in atherosclerotic obstruction of coronary arteries.

A total of 112 hearts with limited local dilatation zones in coronary arteries (antiocclusion factor) selected from 500 patients dead from chronic forms of coronary heart disease were studied by postmortem contrast polypositional coronarography and cardiometry. A relationship between antiocclusion factor, on the one hand, and coronary artery stenosis and degree of vascularization of the left ventricular wall, on the other, was shown. The adaptation role of antiocclusion factor in coronary blood flow disorders caused by atherosclerotic obstruction (stenosis, occlusion, thrombosis) of the major coronary arteries was demonstrated. The incidence of antiocclusion factor in individual segments of coronary arteries depending on the type of atherosclerotic involvement and index of myocardial blood supply was determined.

Pathomorphology of myocardial bridges and their role in the pathogenesis of coronary disease.

The hearts of patients who died of coronary disease and had myocardial bridges were studied by postmortem coronary angiography, cardioventriculography, and complex pathomorphological analysis. The relationship between the incidence and pathomorphology of myocardial bridges, on the one hand, and the type of blood supply, segmentary topography of the major coronary arteries, geometry of the left ventricle, and coronary changes in different forms of coronary disease, on the other, was analyzed. Diagnostic criteria were developed and the main components of the etiology, patho- and thanatogenesis in coronary patients with coronary arteries not affected by atherosclerosis are presented.

[Post-infarction heart (pathomorphological criteria for evaluating ventricular remodeling)]. / Postinfarktnoe serdtse (patomorfologicheskie kriterii otsenki remodelirovaniia zheludochkov).

Two hundred and sixty hearts from patients who had died in different periods after myocardial infarction (MI) and 40 control hearts were morphologically studied. Dilated, hypertrophic, aneurysmal, and endocardial variants of heart remodelling after MI are distinguished and their detailed characteristics are given. These variants underlie intracardiac hemodynamic changes and tanatogenesis.

[Comparative incidence of protrusive atheromatous plaques of the thoracic artery in patients with atrial fluter and atrial fibrillation]. / Fréquence comparée des plaques athéromateuses protrusives de l'aorte thoracique chez les patients en flutter et en fibrillation auriculaire.

Although it has been demonstrated recently that in patients with atrial fibrillation, protrusive atheromatous plaques of the thoracic aorta (thickness 4 mm) and left atrial abnormalities such as thrombosis, spontaneous contrast and low atrial blood flow velocities carry an additional embolic risk, this has not yet been studied in atrial flutter. Out of 2493 patients undergoing transoesophageal echocardiography between September 1993 and December 1997, 271 consecutive patients in atrial flutter (N = 41) or fibrillation (N = 230) for over 48 hours, underwent transoesophageal echocardiography before cardioversion. Patients with atrial flutter were compared with those with atrial fibrillation. Their characteristics were comparable with respect to age (68 +/- 13 and 67 +/- 12 years respectively, p = 0.628), sex ratio (men 66 and 54% respectively, p = 0.212), previous thromboembolic disease (5 and 15% respectively, p = 0.126). The incidence of protrusive aortic atheroma (12 and 11% respectively, p = 0.919), of spontaneous contrast in the thoracic aorta (15 and 14% respectively, p = 0.847) were identical in both groups. The left atrium was significantly smaller (3.1 +/- 0.7 and 6 +/- 3 cm2 respectively, p = 0.001), spontaneous atrial contrast less frequent (17 and 37% respectively, p = 0.024) and the velocities of atrial emptying higher (47 +/- 10 and 30 +/- 10 cm/s respectively, p = 0.030) in patients with flutter compared with atrial fibrillation. There was no difference in left ventricular fractional shortening (30 +/- 10 and 33 +/- 13% respectively, p = 0.630), the presence of rheumatic valvular disease (5 and 12%, p = 0.301), left atrial diameter (43 +/- 7 and 45 +/- 8, p = 0.134), right atrial surface area (16 +/- 4 and 17 +/- 6 cm2, p = 0.384) or in intraatrial thrombosis (2 and 3%, p = 0.888) respectively. These results show a high prevalence of protrusive atheroma of the thoracic aorta both in atrial flutter and in atrial fibrillation, and fewer left atrial abnormalities in patients with flutter.