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Bongani M Mayosi - One of the best experts on this subject based on the ideXlab platform.
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Detectable prednisolone is delayed in pericardial fluid, compared with plasma of patients with Tuberculous Pericarditis: A pilot study.
International journal of cardiology. Heart & vasculature, 2019Co-Authors: Justin Shenje, Mpiko Ntsekhe, Bongani M Mayosi, Tawanda Gumbo, Lubbe Wiesner, Ian L. RossAbstract:Abstract Background In patients with Tuberculous Pericarditis [TBP] adjunctive prednisolone reduces the incidence of constrictive Pericarditis. It is unknown whether prednisolone permeates adequately into pericardial fluid. Drug measurements in pericardial fluid require invasive procedures, and thus less invasive methods are needed to perform full pharmacokinetic characterization of prednisolone in large numbers of patients. We sought to evaluate the relationship between prednisolone concentrations in pericardial fluid, plasma, and saliva. Methods Plasma, pericardial fluid, and saliva samples were collected at 7 time points from TBP patients randomized to 120 mg prednisolone or placebo. Compartmental pharmacokinetic parameters, peak concentration [Cmax], and 0–24 h area under the concentration-time curve [AUC0–24] were identified in plasma, saliva and pericardial fluid. Results There were five patients each in the prednisolone and placebo groups. Prednisolone concentrations were best described using a one compartment model. The absorption half-life into plasma was 1 h, while that into pericardial fluid was 9.4 h, which led to a median time-to-maximum concentration in plasma of 2.0 h versus 5.0 h in pericardial fluid [p = 0.048]. The concentration-time profiles in pericardial fluid versus plasma exhibited system hysteresis. The pericardial fluid-to-plasma Cmax peak concentration ratio was 0.28 (p = 0.032), while the AUC0–24 ratio was 0.793. The concentration-time profiles in saliva had a similar shape to those in plasma, but the saliva-to-plasma Cmax was 0.59 [p = 0.032]. Conclusion The prednisolone AUC0–24 achieved in pericardial fluid approximates that in plasma, but the Cmax is low due to delayed absorption. Saliva can be used as surrogate sampling site for pericardial fluid prednisolone.
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interventions for treating Tuberculous Pericarditis
Cochrane Database of Systematic Reviews, 2017Co-Authors: Charles Shey Wiysonge, Mpiko Ntsekhe, Freedom Gumedze, Jimmy Volmink, Shaheen Pandie, Lehana Thabane, Dumisani Majombozi, Bongani M MayosiAbstract:Background Tuberculous Pericarditis can impair the heart's function and cause death; long term, it can cause the membrane to fibrose and constrict causing heart failure. In addition to antiTuberculous chemotherapy, treatments include corticosteroids, drainage, and surgery. Objectives To assess the effects of treatments for Tuberculous Pericarditis. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register (27 March 2017); the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library (2017, Issue 2); MEDLINE (1966 to 27 March 2017); Embase (1974 to 27 March 2017); and LILACS (1982 to 27 March 2017). In addition we searched the metaRegister of Controlled Trials (mRCT) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal using 'tuberculosis' and 'pericard*' as search terms on 27 March 2017. We searched ClinicalTrials.gov and contacted researchers in the field of Tuberculous Pericarditis. This is a new version of the original 2002 review. Selection criteria We included randomized controlled trials (RCTs) and quasi-RCTs. Data collection and analysis Two review authors independently screened search outputs, evaluated study eligibility, assessed risk of bias, and extracted data; and we resolved any discrepancies by discussion and consensus. One trial assessed the effects of both corticosteroid and Mycobacterium indicus pranii treatment in a two-by-two factorial design; we excluded data from the group that received both interventions. We conducted fixed-effect meta-analysis and assessed the certainty of the evidence using the GRADE approach. Main results Seven trials met the inclusion criteria; all were from sub-Saharan Africa and included 1959 participants, with 1051/1959 (54%) HIV-positive. All trials evaluated corticosteroids and one each evaluated colchicine, M. indicus pranii immunotherapy, and open surgical drainage. Four trials (1841 participants) were at low risk of bias, and three trials (118 participants) were at high risk of bias. In people who are not infected with HIV, corticosteroids may reduce deaths from all causes (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.59 to 1.09; 660 participants, 4 trials, low certainty evidence) and the need for repeat pericardiocentesis (RR 0.85, 95% CI 0.70 to 1.04; 492 participants, 2 trials, low certainty evidence). Corticosteroids probably reduce deaths from Pericarditis (RR 0.39, 95% CI 0.19 to 0.80; 660 participants, 4 trials, moderate certainty evidence). However, we do not know whether or not corticosteroids have an effect on constriction or cancer among HIV-negative people (very low certainty evidence). In people living with HIV, only 19.9% (203/1959) were on antiretroviral drugs. Corticosteroids may reduce constriction (RR 0.55, 0.26 to 1.16; 575 participants, 3 trials, low certainty evidence). It is uncertain whether corticosteroids have an effect on all-cause death or cancer (very low certainty evidence); and may have little or no effect on repeat pericardiocentesis (RR 1.02, 0.89 to 1.18; 517 participants, 2 trials, low certainty evidence). For colchicine among people living with HIV, we found one small trial (33 participants) which had insufficient data to make any conclusions about any effects on death or constrictive Pericarditis. Irrespective of HIV status, due to very low certainty evidence from one trial, it is uncertain whether adding M. indicus pranii immunotherapy to antiTuberculous drugs has an effect on any outcome. Open surgical drainage for effusion may reduce repeat pericardiocentesis In HIV-negative people (RR 0.23, 95% CI 0.07 to 0.76; 122 participants, 1 trial, low certainty evidence) but may make little or no difference to other outcomes. We did not find an eligible trial that assessed the effects of open surgical drainage in people living with HIV. The review authors found no eligible trials that examined the length of antiTuberculous treatment needed nor the effects of other adjunctive treatments for Tuberculous Pericarditis. Authors' conclusions For HIV-negative patients, corticosteroids may reduce death. For HIV-positive patients not on antiretroviral drugs, corticosteroids may reduce constriction. For HIV-positive patients with good antiretroviral drug viral suppression, clinicians may consider the results from HIV-negative patients more relevant. Further research may help evaluate percutaneous drainage of the pericardium under local anaesthesia, the timing of pericardiectomy in Tuberculous constrictive Pericarditis, and new antibiotic regimens.
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Global burden of cardiovascular disease. Heart 2007; 93(10
2016Co-Authors: Bongani M Mayosi, J Floor, Old Main Building, Town South AfricaAbstract:Heart failure in sub-Saharan Africans is mainly due to non-ischaemic causes, such as hypertension, rheumatic heart disease, cardiomyopathy and Pericarditis. The two endemic diseases that are major contributors to the clinical syndrome of heart failure in Africa are cardiomyopathy and Pericarditis. The major forms of endemic cardiomyopathy are idiopathic dilated cardiomyopathy, peripartum cardiomyopathy and endo-myocardial fibrosis. Endomyocardial fibrosis, which affects children, has the worst prognosis. Other cardiomyopathies have similar epidemiological characteristics to those of other populations in the world. HIV infection is associated with occurrence of HIV-associated cardiomyopathy in patients with advanced immunosuppression, and the rise in the incidence of Tuberculous Pericarditis. HIV-associated Tuberculous Pericarditis is characterised by larger pericardial effusion, a greater frequency of myoPericarditis, and a higher mortality than in people without AIDS. Population-based studies on the epidemiology of heart failure, cardiomyopathy and Pericarditis in Africans, and studies of new interventions to reduce mortality, particularly in endomyocardial fibrosis and Tuberculous Pericarditis, are needed
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Tuberculous Pericarditis is multibacillary and bacterial burden drives high mortality
EBioMedicine, 2015Co-Authors: Jotam G Pasipanodya, Mpiko Ntsekhe, Tawanda Gumbo, Freedom Gumedze, Shaheen Pandie, Mwenya Mubanga, Beki Themba Magazi, Landon Myer, Bongani M MayosiAbstract:South African Medical Research Council (MRC) for self-initiated research from November 2012 to April 2015, the Lily and Ernst Hausmann Research Trust, and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01AI079497).
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host directed therapies for Tuberculous Pericarditis
International Journal of Infectious Diseases, 2015Co-Authors: Alimuddin Zumla, Markus Maeurer, Guido Moll, Bongani M MayosiAbstract:TB Pericarditis is associated with significant inflammatory and immune responses which can paradoxically cause injury to the pericardium and myocardium. Management with anti-TB therapy alone does not prevent complications or reduce mortality. Thus the prevailing view is that adjunct host-directed therapies such as use of glucocorticoid treatment could attenuate destructive inflammatory responses and improve morbidity and mortality rates. A recent trial showed no advantage of using adjunct corticosteroid treatment on the combined endpoint of death, cardiac tamponade or constriction. The current lack of effective medical treatment for reducing the significant morbidity and mortality associated with TB Pericarditis, highlights the urgent need for newer approaches to treating the disease. Newer treatment options for Pericarditis using adjunct host-directed therapies, including autologous bone-marrow-derived Mesenchymal Stromal Cells (MSCs) therapy, now require evaluation in randomized placebo-controlled controlled trials.
Mpiko Ntsekhe - One of the best experts on this subject based on the ideXlab platform.
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the immunopathogenesis of Tuberculous Pericarditis
Microbes and Infection, 2020Co-Authors: Mpiko Ntsekhe, Patrick J Howlett, Elsa Du Bruyn, Hazel Morrison, Isiguzo C Godsent, Katalin A Wilkinson, Robert J WilkinsonAbstract:Tuberculous Pericarditis is a severe form of extrapulmonary tuberculosis and is the commonest cause of pericardial effusion in high incidence settings. Mortality ranges between 8 and 34%, and it is the leading cause of pericardial constriction in Africa and Asia. Current understanding of the disease is based on models derived from studies performed in the 1940-50s. This review summarises recent advances in the histology, microbiology and immunology of Tuberculous Pericarditis, with special focus on the effect of Human Immunodeficiency Virus (HIV) and the determinants of constriction.
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diagnosis and management of Tuberculous Pericarditis what is new
Current Cardiology Reports, 2020Co-Authors: Godsent Isiguzo, Elsa Du Bruyn, Patrick Howlett, Mpiko NtsekheAbstract:This review provides an update on the immunopathogenesis of Tuberculous Pericarditis (TBP), investigations to confirm Tuberculous etiology, the limitations of anti-Tuberculous therapy (ATT), and recent efficacy trials. A profibrotic immune response characterizes TBP, with low levels of AcSDKP, high levels of γ-interferon and IL-10 in the pericardium, and high levels of TGF-β and IL-10 in the blood. These findings may have implications for future therapeutic targets. Despite advances in nucleic acid amplification approaches, these tests remain disappointing for TBP. Trials of corticosteroids and colchicine have had mixed results, with no impact on mortality, evidence of a reduction in rates of constrictive Pericarditis and potential harm in those with advanced HIV. Small studies suggest that ATT penetrates the pericardium poorly. Given that there is a close association between high bacillary burden and mortality, a rethink about the optimal drug doses and duration may be required. The high mortality and morbidity from TBP despite use of anti-Tuberculous drugs call for researches targeting host-directed immunological determinants of treatment outcome. There is also a need for the identification of steps in clinical management where interventions are needed to improve outcomes.
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Detectable prednisolone is delayed in pericardial fluid, compared with plasma of patients with Tuberculous Pericarditis: A pilot study.
International journal of cardiology. Heart & vasculature, 2019Co-Authors: Justin Shenje, Mpiko Ntsekhe, Bongani M Mayosi, Tawanda Gumbo, Lubbe Wiesner, Ian L. RossAbstract:Abstract Background In patients with Tuberculous Pericarditis [TBP] adjunctive prednisolone reduces the incidence of constrictive Pericarditis. It is unknown whether prednisolone permeates adequately into pericardial fluid. Drug measurements in pericardial fluid require invasive procedures, and thus less invasive methods are needed to perform full pharmacokinetic characterization of prednisolone in large numbers of patients. We sought to evaluate the relationship between prednisolone concentrations in pericardial fluid, plasma, and saliva. Methods Plasma, pericardial fluid, and saliva samples were collected at 7 time points from TBP patients randomized to 120 mg prednisolone or placebo. Compartmental pharmacokinetic parameters, peak concentration [Cmax], and 0–24 h area under the concentration-time curve [AUC0–24] were identified in plasma, saliva and pericardial fluid. Results There were five patients each in the prednisolone and placebo groups. Prednisolone concentrations were best described using a one compartment model. The absorption half-life into plasma was 1 h, while that into pericardial fluid was 9.4 h, which led to a median time-to-maximum concentration in plasma of 2.0 h versus 5.0 h in pericardial fluid [p = 0.048]. The concentration-time profiles in pericardial fluid versus plasma exhibited system hysteresis. The pericardial fluid-to-plasma Cmax peak concentration ratio was 0.28 (p = 0.032), while the AUC0–24 ratio was 0.793. The concentration-time profiles in saliva had a similar shape to those in plasma, but the saliva-to-plasma Cmax was 0.59 [p = 0.032]. Conclusion The prednisolone AUC0–24 achieved in pericardial fluid approximates that in plasma, but the Cmax is low due to delayed absorption. Saliva can be used as surrogate sampling site for pericardial fluid prednisolone.
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interventions for treating Tuberculous Pericarditis
Cochrane Database of Systematic Reviews, 2017Co-Authors: Charles Shey Wiysonge, Mpiko Ntsekhe, Freedom Gumedze, Jimmy Volmink, Shaheen Pandie, Lehana Thabane, Dumisani Majombozi, Bongani M MayosiAbstract:Background Tuberculous Pericarditis can impair the heart's function and cause death; long term, it can cause the membrane to fibrose and constrict causing heart failure. In addition to antiTuberculous chemotherapy, treatments include corticosteroids, drainage, and surgery. Objectives To assess the effects of treatments for Tuberculous Pericarditis. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register (27 March 2017); the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library (2017, Issue 2); MEDLINE (1966 to 27 March 2017); Embase (1974 to 27 March 2017); and LILACS (1982 to 27 March 2017). In addition we searched the metaRegister of Controlled Trials (mRCT) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal using 'tuberculosis' and 'pericard*' as search terms on 27 March 2017. We searched ClinicalTrials.gov and contacted researchers in the field of Tuberculous Pericarditis. This is a new version of the original 2002 review. Selection criteria We included randomized controlled trials (RCTs) and quasi-RCTs. Data collection and analysis Two review authors independently screened search outputs, evaluated study eligibility, assessed risk of bias, and extracted data; and we resolved any discrepancies by discussion and consensus. One trial assessed the effects of both corticosteroid and Mycobacterium indicus pranii treatment in a two-by-two factorial design; we excluded data from the group that received both interventions. We conducted fixed-effect meta-analysis and assessed the certainty of the evidence using the GRADE approach. Main results Seven trials met the inclusion criteria; all were from sub-Saharan Africa and included 1959 participants, with 1051/1959 (54%) HIV-positive. All trials evaluated corticosteroids and one each evaluated colchicine, M. indicus pranii immunotherapy, and open surgical drainage. Four trials (1841 participants) were at low risk of bias, and three trials (118 participants) were at high risk of bias. In people who are not infected with HIV, corticosteroids may reduce deaths from all causes (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.59 to 1.09; 660 participants, 4 trials, low certainty evidence) and the need for repeat pericardiocentesis (RR 0.85, 95% CI 0.70 to 1.04; 492 participants, 2 trials, low certainty evidence). Corticosteroids probably reduce deaths from Pericarditis (RR 0.39, 95% CI 0.19 to 0.80; 660 participants, 4 trials, moderate certainty evidence). However, we do not know whether or not corticosteroids have an effect on constriction or cancer among HIV-negative people (very low certainty evidence). In people living with HIV, only 19.9% (203/1959) were on antiretroviral drugs. Corticosteroids may reduce constriction (RR 0.55, 0.26 to 1.16; 575 participants, 3 trials, low certainty evidence). It is uncertain whether corticosteroids have an effect on all-cause death or cancer (very low certainty evidence); and may have little or no effect on repeat pericardiocentesis (RR 1.02, 0.89 to 1.18; 517 participants, 2 trials, low certainty evidence). For colchicine among people living with HIV, we found one small trial (33 participants) which had insufficient data to make any conclusions about any effects on death or constrictive Pericarditis. Irrespective of HIV status, due to very low certainty evidence from one trial, it is uncertain whether adding M. indicus pranii immunotherapy to antiTuberculous drugs has an effect on any outcome. Open surgical drainage for effusion may reduce repeat pericardiocentesis In HIV-negative people (RR 0.23, 95% CI 0.07 to 0.76; 122 participants, 1 trial, low certainty evidence) but may make little or no difference to other outcomes. We did not find an eligible trial that assessed the effects of open surgical drainage in people living with HIV. The review authors found no eligible trials that examined the length of antiTuberculous treatment needed nor the effects of other adjunctive treatments for Tuberculous Pericarditis. Authors' conclusions For HIV-negative patients, corticosteroids may reduce death. For HIV-positive patients not on antiretroviral drugs, corticosteroids may reduce constriction. For HIV-positive patients with good antiretroviral drug viral suppression, clinicians may consider the results from HIV-negative patients more relevant. Further research may help evaluate percutaneous drainage of the pericardium under local anaesthesia, the timing of pericardiectomy in Tuberculous constrictive Pericarditis, and new antibiotic regimens.
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the importance of perseverance pilot studies and the search for effective adjuvant therapies in the management of Tuberculous Pericarditis
Cardiovascular Journal of Africa, 2016Co-Authors: Arthur Mutyaba, Mpiko NtsekheAbstract:Tuberculous Pericarditis remains one of the most feared manifestations of extra-pulmonary tuberculosis (TB). The relatively high morbidity and mortality rates associated with the condition arise via two distinct mechanisms. The first is related to the combined impact of the virulence of Mycobacterium tuberculosis (MTb) itself and TB-induced dysregulated immune responses in both HIV-positive and -negative individuals, resulting in disseminated infection, multi-organ involvement, and prolonged acute infection. The second mechanism is related to compressive pericardial disease (cardiac tamponade, effusive constrictive Pericarditis and constrictive Pericarditis), which can cause significant compromise of cardiovascular function.
A F Doubell - One of the best experts on this subject based on the ideXlab platform.
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Experience with adjunctive corticosteroids in managing Tuberculous Pericarditis
2016Co-Authors: Helmuth Reuter, L J Burgess, Vernon J Louw, A F DoubellAbstract:Objectives: To compare the efficacy of intrapericardial corticosteroid therapy to either oral corticosteroid thera-py or intrapericardial placebo in addition to closed peri-cardiocentesis and anti-Tuberculous therapy in patients with Tuberculous Pericarditis. Methods: Patients with large pericardial effusions requir-ing pericardiocentesis were included. A short-course anti-Tuberculous regimen was initiated and patients were randomised to one of three treatment groups: 200 mg intrapericardial triamcinolone hexacetonide; oral pred-nisone plus intrapericardial placebo; or 5 ml intraperi-cardial 0.9 % saline (placebo). Patients were followed up for at least one year. Results: Fifty-seven patients were included in the study; 21 tested HIV positive (36.8%). Forty (70.0%) ha
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diagnosing Tuberculous Pericarditis
QJM: An International Journal of Medicine, 2006Co-Authors: Helmuth Reuter, L J Burgess, W Van Vuuren, A F DoubellAbstract:Summary Background: Definitive diagnosis of Tuberculous Pericarditis requires isolation of the tubercle bacillus from pericardial fluid, but isolating the organism is often difficult. Aim: To improve diagnostic efficiency for Tuberculous Pericarditis, using available tests. Design: Prospective observational study. Methods: Consecutive patients (n ¼ 233) presenting with pericardial effusions underwent a predetermined diagnostic work-up. This included (i) clinical examination; (ii) pericardial fluid tests: biochemistry, microbiology, cytology, differential white blood cell (WBC) count, gamma interferon (IFN-g), adenosine deaminase (ADA) levels, polymerase chain reaction testing for Mycobacterium tuberculosis; (iii) HIV; (iv) sputum smear and culture; (v) blood biochemistry; and (vi) differential WBC count. A model was developed using ‘classification and regression tree’ analysis. The cut-off for the total diagnostic index (DI) was optimized using receiver operating characteristic (ROC) curves.
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experience with adjunctive corticosteroids in managing Tuberculous Pericarditis
Cardiovascular journal of South Africa : official journal for Southern Africa Cardiac Society [and] South African Society of Cardiac Practitioners, 2006Co-Authors: Helmuth Reuter, L J Burgess, Vernon J Louw, A F DoubellAbstract:Summary Objectives: To compare the efficacy of intrapericardial corticosteroid therapy to either oral corticosteroid therapy or intrapericardial placebo in addition to closed pericardiocentesis and anti-Tuberculous therapy in patients with Tuberculous Pericarditis. Methods: Patients with large pericardial effusions requiring pericardiocentesis were included. A short-course anti-Tuberculous regimen was initiated and patients were randomised to one of three treatment groups: 200 mg intrapericardial triamcinolone hexacetonide; oral prednisone plus intrapericardial placebo; or 5 ml intrapericardial 0.9% saline (placebo). Patients were followed up for at least one year. Results: Fifty-seven patients were included in the study; 21 tested HIV positive (36.8%). Forty (70.0%) had microbiological and/or histological evidence of tuberculosis, and 17 (30.0%) had a diagnosis based on clinical and laboratory data. All patients responded well to initial pericardiocentesis. However, nine patients (16.0%) were lost to follow up. The hospitalisation duration for the steroid groups was shorter than for the placebo group. This difference was not significant. Complications were similar for all arms. Conclusions: Intrapericardial and systemic corticosteroids were well tolerated but did not improve the clinical outcome. The standard six-month regimen was effective regardless of HIV infection. The potential benefits from adjunctive corticosteroids in the management of effusive Tuberculous Pericarditis could not be demonstrated in this three-year study.
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experience with adjunctive corticosteroids in managing Tuberculous Pericarditis cardiovascular topics
Cardiovascular journal of South Africa, 2006Co-Authors: Helmuth Reuter, L J Burgess, Vernon J Louw, A F DoubellAbstract:Objectives: To compare the efficacy of intrapericardial corticosteroid therapy to either oral corticosteroid therapy or intrapericardial placebo in addition to closed pericardiocentesis and anti-Tuberculous therapy in patients with Tuberculous Pericarditis. Methods: Patients with large pericardial effusions requiring pericardiocentesis were included. A short-course anti-Tuberculous regimen was initiated and patients were randomised to one of three treatment groups: 200 mg intrapericardial triamcinolone hexacetonide; oral prednisone plus intrapericardial placebo; or 5 ml intrapericardial 0.9% saline (placebo). Patients were followed up for at least one year. Results: Fifty-seven patients were included in the study; 21 tested HIV positive (36.8%). Forty (70.0%) had microbiological and / or histological evidence of tuberculosis, and 17 (30.0%) had a diagnosis based on clinical and laboratory data. All patients responded well to initial pericardiocentesis. However, nine patients (16.0%) were lost to follow up. The hospitalisation duration for the steroid groups was shorter than for the placebo group. This difference was not significant. Complications were similar for all arms. Conclusions: Intrapericardial and systemic corticosteroids were well tolerated but did not improve the clinical outcome. The standard six-month regimen was effective regardless of HIV infection. The potential benefits from adjunctive corticosteroids in the management of effusive Tuberculous Pericarditis could not be demonstrated in this three-year study.
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adenosine deaminase activity more than a diagnostic tool in Tuberculous Pericarditis
Cardiovascular journal of South Africa : official journal for Southern Africa Cardiac Society [and] South African Society of Cardiac Practitioners, 2005Co-Authors: Helmuth Reuter, L J Burgess, Machteld E Carstens, A F DoubellAbstract:Summary Aim: To improve the understanding of factors that influence adenosine deaminase (ADA) activity in large peri cardial effusions. Methods: A prospective study was carried out at Tygerberg Academic Hospital, South Africa. Patients underwent echocardiographically guided pericardiocentesis. ADA activity, as well as biochemistry, haematology, cytology, and in some cases, histology, were determined. Human immunodeficiency virus (HIV) status was assessed in all patients. Results: Two hundred and thirty-three patients presented to Tygerberg Hospital with large pericardial effusions requiring pericardiocentesis. Tuberculous Pericarditis accounted for 162 effusions (69.5%). An ADA cut-off level of 40 U/l resulted in a test sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic efficiency of 84.0%, 80.0%, 91.0%, 66.0% and 83.0%, respectively. Pericardial exudates with an ADA activity ≥ 40 U/l were associated with increased total leukocyte and neutro phil counts. Patients with Tuberculous Pericarditis and ADA ≥ 40 U/l also had increased lymphocyte counts. Pericardial ADA activity < 30 U/l was associated with severe depletion of CD4 cell counts in HIV-positive patients. ADA levels were higher in cases with histological evidence of granulomatous inflammation than in cases with serofibrinous Pericarditis. Conclusions: An ADA cut-off level of 40 U/l results in best diagnostic test results. ADA production appears to be influenced by factors associated with the antiTuberculous immune response. Cardiovasc J South Afr 2005; 16: 143–147. www.cvjsa.co.za Tuberculosis (TB) is the most important cause of serious pericardial disease in sub-Saharan Africa, and this is likely to worsen with the increase in the human immunodeficiency virus (HIV) epidemic. 1-3 It is often difficult to establish a definite diagnosis in Tuberculous Pericarditis, and a number of diagnostic tests are required to support a clinical diagnosis. 3,4 In countries where TB is endemic, the increase in adenosine deaminase (ADA) activity observed in the pericardial fluid of patients with TB has been used to establish the diagnosis of Tuberculous Pericarditis. 4-7
Helmuth Reuter - One of the best experts on this subject based on the ideXlab platform.
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Experience with adjunctive corticosteroids in managing Tuberculous Pericarditis
2016Co-Authors: Helmuth Reuter, L J Burgess, Vernon J Louw, A F DoubellAbstract:Objectives: To compare the efficacy of intrapericardial corticosteroid therapy to either oral corticosteroid thera-py or intrapericardial placebo in addition to closed peri-cardiocentesis and anti-Tuberculous therapy in patients with Tuberculous Pericarditis. Methods: Patients with large pericardial effusions requir-ing pericardiocentesis were included. A short-course anti-Tuberculous regimen was initiated and patients were randomised to one of three treatment groups: 200 mg intrapericardial triamcinolone hexacetonide; oral pred-nisone plus intrapericardial placebo; or 5 ml intraperi-cardial 0.9 % saline (placebo). Patients were followed up for at least one year. Results: Fifty-seven patients were included in the study; 21 tested HIV positive (36.8%). Forty (70.0%) ha
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diagnosing Tuberculous Pericarditis
QJM: An International Journal of Medicine, 2006Co-Authors: Helmuth Reuter, L J Burgess, W Van Vuuren, A F DoubellAbstract:Summary Background: Definitive diagnosis of Tuberculous Pericarditis requires isolation of the tubercle bacillus from pericardial fluid, but isolating the organism is often difficult. Aim: To improve diagnostic efficiency for Tuberculous Pericarditis, using available tests. Design: Prospective observational study. Methods: Consecutive patients (n ¼ 233) presenting with pericardial effusions underwent a predetermined diagnostic work-up. This included (i) clinical examination; (ii) pericardial fluid tests: biochemistry, microbiology, cytology, differential white blood cell (WBC) count, gamma interferon (IFN-g), adenosine deaminase (ADA) levels, polymerase chain reaction testing for Mycobacterium tuberculosis; (iii) HIV; (iv) sputum smear and culture; (v) blood biochemistry; and (vi) differential WBC count. A model was developed using ‘classification and regression tree’ analysis. The cut-off for the total diagnostic index (DI) was optimized using receiver operating characteristic (ROC) curves.
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experience with adjunctive corticosteroids in managing Tuberculous Pericarditis
Cardiovascular journal of South Africa : official journal for Southern Africa Cardiac Society [and] South African Society of Cardiac Practitioners, 2006Co-Authors: Helmuth Reuter, L J Burgess, Vernon J Louw, A F DoubellAbstract:Summary Objectives: To compare the efficacy of intrapericardial corticosteroid therapy to either oral corticosteroid therapy or intrapericardial placebo in addition to closed pericardiocentesis and anti-Tuberculous therapy in patients with Tuberculous Pericarditis. Methods: Patients with large pericardial effusions requiring pericardiocentesis were included. A short-course anti-Tuberculous regimen was initiated and patients were randomised to one of three treatment groups: 200 mg intrapericardial triamcinolone hexacetonide; oral prednisone plus intrapericardial placebo; or 5 ml intrapericardial 0.9% saline (placebo). Patients were followed up for at least one year. Results: Fifty-seven patients were included in the study; 21 tested HIV positive (36.8%). Forty (70.0%) had microbiological and/or histological evidence of tuberculosis, and 17 (30.0%) had a diagnosis based on clinical and laboratory data. All patients responded well to initial pericardiocentesis. However, nine patients (16.0%) were lost to follow up. The hospitalisation duration for the steroid groups was shorter than for the placebo group. This difference was not significant. Complications were similar for all arms. Conclusions: Intrapericardial and systemic corticosteroids were well tolerated but did not improve the clinical outcome. The standard six-month regimen was effective regardless of HIV infection. The potential benefits from adjunctive corticosteroids in the management of effusive Tuberculous Pericarditis could not be demonstrated in this three-year study.
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experience with adjunctive corticosteroids in managing Tuberculous Pericarditis cardiovascular topics
Cardiovascular journal of South Africa, 2006Co-Authors: Helmuth Reuter, L J Burgess, Vernon J Louw, A F DoubellAbstract:Objectives: To compare the efficacy of intrapericardial corticosteroid therapy to either oral corticosteroid therapy or intrapericardial placebo in addition to closed pericardiocentesis and anti-Tuberculous therapy in patients with Tuberculous Pericarditis. Methods: Patients with large pericardial effusions requiring pericardiocentesis were included. A short-course anti-Tuberculous regimen was initiated and patients were randomised to one of three treatment groups: 200 mg intrapericardial triamcinolone hexacetonide; oral prednisone plus intrapericardial placebo; or 5 ml intrapericardial 0.9% saline (placebo). Patients were followed up for at least one year. Results: Fifty-seven patients were included in the study; 21 tested HIV positive (36.8%). Forty (70.0%) had microbiological and / or histological evidence of tuberculosis, and 17 (30.0%) had a diagnosis based on clinical and laboratory data. All patients responded well to initial pericardiocentesis. However, nine patients (16.0%) were lost to follow up. The hospitalisation duration for the steroid groups was shorter than for the placebo group. This difference was not significant. Complications were similar for all arms. Conclusions: Intrapericardial and systemic corticosteroids were well tolerated but did not improve the clinical outcome. The standard six-month regimen was effective regardless of HIV infection. The potential benefits from adjunctive corticosteroids in the management of effusive Tuberculous Pericarditis could not be demonstrated in this three-year study.
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adenosine deaminase activity more than a diagnostic tool in Tuberculous Pericarditis
Cardiovascular journal of South Africa : official journal for Southern Africa Cardiac Society [and] South African Society of Cardiac Practitioners, 2005Co-Authors: Helmuth Reuter, L J Burgess, Machteld E Carstens, A F DoubellAbstract:Summary Aim: To improve the understanding of factors that influence adenosine deaminase (ADA) activity in large peri cardial effusions. Methods: A prospective study was carried out at Tygerberg Academic Hospital, South Africa. Patients underwent echocardiographically guided pericardiocentesis. ADA activity, as well as biochemistry, haematology, cytology, and in some cases, histology, were determined. Human immunodeficiency virus (HIV) status was assessed in all patients. Results: Two hundred and thirty-three patients presented to Tygerberg Hospital with large pericardial effusions requiring pericardiocentesis. Tuberculous Pericarditis accounted for 162 effusions (69.5%). An ADA cut-off level of 40 U/l resulted in a test sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic efficiency of 84.0%, 80.0%, 91.0%, 66.0% and 83.0%, respectively. Pericardial exudates with an ADA activity ≥ 40 U/l were associated with increased total leukocyte and neutro phil counts. Patients with Tuberculous Pericarditis and ADA ≥ 40 U/l also had increased lymphocyte counts. Pericardial ADA activity < 30 U/l was associated with severe depletion of CD4 cell counts in HIV-positive patients. ADA levels were higher in cases with histological evidence of granulomatous inflammation than in cases with serofibrinous Pericarditis. Conclusions: An ADA cut-off level of 40 U/l results in best diagnostic test results. ADA production appears to be influenced by factors associated with the antiTuberculous immune response. Cardiovasc J South Afr 2005; 16: 143–147. www.cvjsa.co.za Tuberculosis (TB) is the most important cause of serious pericardial disease in sub-Saharan Africa, and this is likely to worsen with the increase in the human immunodeficiency virus (HIV) epidemic. 1-3 It is often difficult to establish a definite diagnosis in Tuberculous Pericarditis, and a number of diagnostic tests are required to support a clinical diagnosis. 3,4 In countries where TB is endemic, the increase in adenosine deaminase (ADA) activity observed in the pericardial fluid of patients with TB has been used to establish the diagnosis of Tuberculous Pericarditis. 4-7
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interventions for treating Tuberculous Pericarditis
Cochrane Database of Systematic Reviews, 2017Co-Authors: Charles Shey Wiysonge, Mpiko Ntsekhe, Freedom Gumedze, Jimmy Volmink, Shaheen Pandie, Lehana Thabane, Dumisani Majombozi, Bongani M MayosiAbstract:Background Tuberculous Pericarditis can impair the heart's function and cause death; long term, it can cause the membrane to fibrose and constrict causing heart failure. In addition to antiTuberculous chemotherapy, treatments include corticosteroids, drainage, and surgery. Objectives To assess the effects of treatments for Tuberculous Pericarditis. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register (27 March 2017); the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library (2017, Issue 2); MEDLINE (1966 to 27 March 2017); Embase (1974 to 27 March 2017); and LILACS (1982 to 27 March 2017). In addition we searched the metaRegister of Controlled Trials (mRCT) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal using 'tuberculosis' and 'pericard*' as search terms on 27 March 2017. We searched ClinicalTrials.gov and contacted researchers in the field of Tuberculous Pericarditis. This is a new version of the original 2002 review. Selection criteria We included randomized controlled trials (RCTs) and quasi-RCTs. Data collection and analysis Two review authors independently screened search outputs, evaluated study eligibility, assessed risk of bias, and extracted data; and we resolved any discrepancies by discussion and consensus. One trial assessed the effects of both corticosteroid and Mycobacterium indicus pranii treatment in a two-by-two factorial design; we excluded data from the group that received both interventions. We conducted fixed-effect meta-analysis and assessed the certainty of the evidence using the GRADE approach. Main results Seven trials met the inclusion criteria; all were from sub-Saharan Africa and included 1959 participants, with 1051/1959 (54%) HIV-positive. All trials evaluated corticosteroids and one each evaluated colchicine, M. indicus pranii immunotherapy, and open surgical drainage. Four trials (1841 participants) were at low risk of bias, and three trials (118 participants) were at high risk of bias. In people who are not infected with HIV, corticosteroids may reduce deaths from all causes (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.59 to 1.09; 660 participants, 4 trials, low certainty evidence) and the need for repeat pericardiocentesis (RR 0.85, 95% CI 0.70 to 1.04; 492 participants, 2 trials, low certainty evidence). Corticosteroids probably reduce deaths from Pericarditis (RR 0.39, 95% CI 0.19 to 0.80; 660 participants, 4 trials, moderate certainty evidence). However, we do not know whether or not corticosteroids have an effect on constriction or cancer among HIV-negative people (very low certainty evidence). In people living with HIV, only 19.9% (203/1959) were on antiretroviral drugs. Corticosteroids may reduce constriction (RR 0.55, 0.26 to 1.16; 575 participants, 3 trials, low certainty evidence). It is uncertain whether corticosteroids have an effect on all-cause death or cancer (very low certainty evidence); and may have little or no effect on repeat pericardiocentesis (RR 1.02, 0.89 to 1.18; 517 participants, 2 trials, low certainty evidence). For colchicine among people living with HIV, we found one small trial (33 participants) which had insufficient data to make any conclusions about any effects on death or constrictive Pericarditis. Irrespective of HIV status, due to very low certainty evidence from one trial, it is uncertain whether adding M. indicus pranii immunotherapy to antiTuberculous drugs has an effect on any outcome. Open surgical drainage for effusion may reduce repeat pericardiocentesis In HIV-negative people (RR 0.23, 95% CI 0.07 to 0.76; 122 participants, 1 trial, low certainty evidence) but may make little or no difference to other outcomes. We did not find an eligible trial that assessed the effects of open surgical drainage in people living with HIV. The review authors found no eligible trials that examined the length of antiTuberculous treatment needed nor the effects of other adjunctive treatments for Tuberculous Pericarditis. Authors' conclusions For HIV-negative patients, corticosteroids may reduce death. For HIV-positive patients not on antiretroviral drugs, corticosteroids may reduce constriction. For HIV-positive patients with good antiretroviral drug viral suppression, clinicians may consider the results from HIV-negative patients more relevant. Further research may help evaluate percutaneous drainage of the pericardium under local anaesthesia, the timing of pericardiectomy in Tuberculous constrictive Pericarditis, and new antibiotic regimens.
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the diagnostic accuracy of pericardial and urinary lipoarabinomannan lam assays in patients with suspected Tuberculous Pericarditis
Scientific Reports, 2016Co-Authors: Shaheen Pandie, Mpiko Ntsekhe, Zita S Kerbelker, Grant Theron, Ureshnie Govender, Jonathan G Peter, R Meldau, Keertan DhedaAbstract:We evaluated the diagnostic accuracy of urinary and pericardial fluid (PF) lipoarabinomannan (LAM) assays in Tuberculous Pericarditis (TBP). From October 2009 through September 2012, 151 patients with TBP were enrolled. Mycobacterium tuberculosis culture and/or pericardial histology were the reference standard for definite TBP. 49% (74/151), 33.1% (50/151) and 17.9% (27/151) of patients had definite-, probable-, and non-TB respectively; 69.5% (105/151) were HIV positive. LAM ELISA had the following sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value and negative predictive values (95% confidence interval): urinary - 17.4% (9.1–30.7), 93.8% (71.7–98.9), 2.8 (0.1–63.3), 0.9 (0.8–0.9), 88.9% (56.5–98.0), and 28.3% (17.9–41.6); PF - 11.6% (6.0–21.3), 88% (70.0–95.8), 0.9 (0.08–12.0), 1.0 (0.9–1.1), 72.7% (43.4–90.1), and 26.6% (18.2–36.9). Sensitivity increased with a CD4 ≤ 100 cells/mm3 from 3.5% to 50% (p < 0.001) for urinary LAM ELISA; for urinary LAM strip test, grade 1 and 2 cut-points performed similarly, irrespective of HIV status or CD4 count. For PF LAM strip tests, switching cut-points from grade 1 to 2 significantly reduced test sensitivity (54.5% versus 19.7%; p < 0.001). Urinary and PF LAM assays have low sensitivity but high specificity for diagnosis of TBP. The sensitivity of urinary LAM is increased in HIV-infected patients with a CD4 ≤ 100 cells/mm3.
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Tuberculous Pericarditis is multibacillary and bacterial burden drives high mortality
EBioMedicine, 2015Co-Authors: Jotam G Pasipanodya, Mpiko Ntsekhe, Tawanda Gumbo, Freedom Gumedze, Shaheen Pandie, Mwenya Mubanga, Beki Themba Magazi, Landon Myer, Bongani M MayosiAbstract:South African Medical Research Council (MRC) for self-initiated research from November 2012 to April 2015, the Lily and Ernst Hausmann Research Trust, and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01AI079497).
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prednisolone and mycobacterium indicus pranii in Tuberculous Pericarditis
The New England Journal of Medicine, 2014Co-Authors: Mpiko Ntsekhe, Freedom Gumedze, Jackie Bosch, Shaheen Pandie, Hyejung Jung, J Pogue, Lehana Thabane, Marek Smieja, Veronica Francis, L JoldersmaAbstract:Background Tuberculous Pericarditis is associated with high morbidity and mortality even if antituberculosis therapy is administered. We evaluated the effects of adjunctive glucocorticoid therapy and Mycobacterium indicus pranii immunotherapy in patients with Tuberculous Pericarditis. Methods Using a 2-by-2 factorial design, we randomly assigned 1400 adults with definite or probable Tuberculous Pericarditis to either prednisolone or placebo for 6 weeks and to either M. indicus pranii or placebo, administered in five injections over the course of 3 months. Two thirds of the participants had concomitant human immunodeficiency virus (HIV) infection. The primary efficacy outcome was a composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive Pericarditis. Results There was no significant difference in the primary outcome between patients who received prednisolone and those who received placebo (23.8% and 24.5%, respectively; hazard ratio, 0.95; 95% confidence interval [CI], 0.77 to 1.18; P = 0.66) or between those who received M. indicus pranii immunotherapy and those who received placebo (25.0% and 24.3%, respectively; hazard ratio, 1.03; 95% CI, 0.82 to 1.29; P = 0.81). Prednisolone therapy, as compared with placebo, was associated with significant reductions in the incidence of constrictive Pericarditis (4.4% vs. 7.8%; hazard ratio, 0.56; 95% CI, 0.36 to 0.87; P = 0.009) and hospitalization (20.7% vs. 25.2%; hazard ratio, 0.79; 95% CI, 0.63 to 0.99; P = 0.04). Both prednisolone and M. indicus pranii, each as compared with placebo, were associated with a significant increase in the incidence of cancer (1.8% vs. 0.6%; hazard ratio, 3.27; 95% CI, 1.07 to 10.03; P = 0.03, and 1.8% vs. 0.5%; hazard ratio, 3.69; 95% CI, 1.03 to 13.24; P = 0.03, respectively), owing mainly to an increase in HIV-associated cancer. Conclusions In patients with Tuberculous Pericarditis, neither prednisolone nor M. indicus pranii had a significant effect on the composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive Pericarditis. (Funded by the Canadian Institutes of Health Research and others; IMPI ClinicalTrials.gov number, NCT00810849.)
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diagnostic accuracy of quantitative pcr xpert mtb rif for Tuberculous Pericarditis compared to adenosine deaminase and unstimulated interferon γ in a high burden setting a prospective study
BMC Medicine, 2014Co-Authors: Shaheen Pandie, Mpiko Ntsekhe, Jonathan Peter, Zita S Kerbelker, Richard Meldau, Grant Theron, Ureshnie Govender, Keertan Dheda, Bongani M MayosiAbstract:Background Tuberculous Pericarditis (TBP) is associated with high morbidity and mortality, and is an important treatable cause of heart failure in developing countries. Tuberculous aetiology of Pericarditis is difficult to diagnose promptly. The utility of the new quantitative PCR test (Xpert MTB/RIF) for the diagnosis of TBP is unknown. This study sought to evaluate the diagnostic accuracy of the Xpert MTB/RIF test compared to pericardial adenosine deaminase (ADA) and unstimulated interferon-gamma (uIFNγ) in suspected TBP.
