Browsing by Author "Hugo-Hamman, Christopher"

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    Open Access
    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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    Open Access
    The South-South partnership to provide cardiac surgery: The Namibian Children Heart Project
    (2018) Shidhika, Fenny Fiindje; Zühlke, Liesl Joanna; Hugo-Hamman, Christopher
    Introduction: Congenital and acquired heart diseases are highly prevalent in developing countries despite limited specialised care. Namibia established a paediatric cardiac service in 2009 with significant human resource and infrastructural constraints. Therefore, patients are referred for cardiac interventions to South Africa. Objectives: To describe the diagnoses, clinical characteristics, interventions, post-operative morbidity and mortality and follow-up of patients referred for care. Methods: Demographics, diagnoses, interventions, intra- and postoperative morbidity and mortality as well as longitudinal follow-up data of all patients referred to South Africa were recorded and analysed. Results: The total cohort constituted 193 patients of which 179 (93%) had congenital and 7% acquired heart disease. The majority of patients (78.8%) travelled more than 400 km to Windhoek prior to transfer. There were 28 percutaneous interventions. Palliative and definitive surgery was performed in 27 and 129 patients respectively. Eighty (80/156, 51.3%) patients had postoperative complications, of which 15 (9.6%) were a direct complication of surgery. Surgical mortality was 8/156 (5.1%, 95% confidence interval 1.2.2-9.8), with a 30- day mortality of 3.2%. Prolonged ICU stay was associated with a 5% increased risk of death (Hazard Ratio 1.05, 95% confidence interval: 1.02-1.08, p=0.001). Follow-up was complete in 151 (78%) patients over seven years. Conclusions: Despite the challenges associated with a cardiac programme referring patients for intervention to a neighbouring country and the adverse characteristics of multiple lesions and complexity associated with late presentation, we report good surgical and interventional outcomes. Our goal remains to develop a comprehensive sustainable cardiac service in Namibia.