Browsing by Author "Okello, Emmy"

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    Data-independent acquisition mass spectrometry in severe rheumatic heart disease (RHD) identifies a proteomic signature showing ongoing inflammation and effectively classifying RHD cases
    (2022-03-22) Salie, M T; Yang, Jing; Ramírez Medina, Carlos R; Zühlke, Liesl J; Chishala, Chishala; Ntsekhe, Mpiko; Gitura, Bernard; Ogendo, Stephen; Okello, Emmy; Lwabi, Peter; Musuku, John; Mtaja, Agnes; Hugo-Hamman, Christopher; El-Sayed, Ahmed; Damasceno, Albertino; Mocumbi, Ana; Bode-Thomas, Fidelia; Yilgwan, Christopher; Amusa, Ganiyu A; Nkereuwem, Esin; Shaboodien, Gasnat; Da Silva, Rachael; Lee, Dave C H; Frain, Simon; Geifman, Nophar; Whetton, Anthony D; Keavney, Bernard; Engel, Mark E
    Background Rheumatic heart disease (RHD) remains a major source of morbidity and mortality in developing countries. A deeper insight into the pathogenetic mechanisms underlying RHD could provide opportunities for drug repurposing, guide recommendations for secondary penicillin prophylaxis, and/or inform development of near-patient diagnostics. Methods We performed quantitative proteomics using Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectrometry (SWATH-MS) to screen protein expression in 215 African patients with severe RHD, and 230 controls. We applied a machine learning (ML) approach to feature selection among the 366 proteins quantifiable in at least 40% of samples, using the Boruta wrapper algorithm. The case–control differences and contribution to Area Under the Receiver Operating Curve (AUC) for each of the 56 proteins identified by the Boruta algorithm were calculated by Logistic Regression adjusted for age, sex and BMI. Biological pathways and functions enriched for proteins were identified using ClueGo pathway analyses. Results Adiponectin, complement component C7 and fibulin-1, a component of heart valve matrix, were significantly higher in cases when compared with controls. Ficolin-3, a protein with calcium-independent lectin activity that activates the complement pathway, was lower in cases than controls. The top six biomarkers from the Boruta analyses conferred an AUC of 0.90 indicating excellent discriminatory capacity between RHD cases and controls. Conclusions These results support the presence of an ongoing inflammatory response in RHD, at a time when severe valve disease has developed, and distant from previous episodes of acute rheumatic fever. This biomarker signature could have potential utility in recognizing different degrees of ongoing inflammation in RHD patients, which may, in turn, be related to prognostic severity.
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    Detecting subclinical anthracycline therapy related cardiac dysfunction in low income country (SATRACD study)
    (2022) Zhang, Wanzhu; Sliwa, Karen; Azibani, Feriel; Okello, Emmy
    Introduction: Anthracycline therapy-related cardiac dysfunction (ATRCD) is the most common chemotherapy-induced cardiovascular toxicity. It begins with subclinical myocardial cell injury that can be detected using speckle tracking echocardiography (STE), together with Troponin-I. Limited availability of STE in Uganda posts challenges in detecting subclinical ATRCD. Anthracycline can also affect cancer survivors' cardiovascular health through altering patients' lipid homoeostasis. This PhD project aims to describe the incidence and predictors of subclinical ATRCD, assess the accuracy of simple echocardiographic parameters on detecting subclinical ATRCD and investigate the lipoprotein subfractions change after anthracycline therapy. Methods and results: Two hundred seven cancer patients who were scheduled for anthracycline based chemotherapy were recruited and followed up to 6 months after ending chemotherapy. Patients' clinical characteristics, laboratory tests, electrocardiogram and echocardiographic data were collected at the baseline and at each follow up visits. Among the 207 patients, 178 (86.0%) were female, with a median age of 42 years. The cumulative incidence of subclinical and clinical ATRCD were 35.0% and 8.8% respectively at the 6 months after ending the therapy. No factor was found to predict subclinical ATRCD in multivariable model. The development of clinical ATRCD associated with HIV infection and development of subclinical ATRCD at the end of anthracycline therapy. The reduction of mitral annular plane systolic excursion (ΔMAPSE) ≥ 2mm or reduction of mitral annular peak systolic velocity (Δ S') ≥ 0.5cm/s from the baseline defined subclinical ATRCD with fairly good accuracy. Very low density lipoprotein subfraction increased and mean low density lipoprotein particle size decreased following anthracycline therapy. Conclusion: There is high incidence of subclinical ATRCD in Uganda cancer patients. Cardiac surveillance at baseline and ending of anthracycline therapy is essential to identify subclinical ATRCD patients who are at high risk of developing clinical ATRCD, particular in HIV positive patients. The conventional echocardiographic parameters ΔMAPSE and ΔS' may be used to screen subclinical ATRCD in resource limited settings. Anthracycline changes lipoprotein subfraction to more atherogenic pattern. Further studies are needed to explore more on its role on lipid metabolism.