Search Results (50)

Cultured epidermal autografts (CEAs) serve as an alternative permanent skin replacement, though high costs often limit their use in resource-constrained settings and to life-saving cases. This case report presents the first documented cosmetic application of a modified CEA technique in a bodybuilder, demonstrating favorable aesthetic outcomes. A 28-year-old Black male with a 20% total body surface area burn sustained in a domestic fire exhibited superficial and deep partial-thickness burns to the face, arms, torso, and feet. Refusing grafts from visible donor sites, treatment using a low-cost modified CEA approach was employed to minimize donor site morbidity. Keratinocytes harvested from a groin biopsy were cultured on Cutimed Sorbact^® (Essity AB, BSN Medical (Pty) Ltd., Pinetown, RSA) dressings with autogenous plasma and hydrogel supplementation and incubated at 37 °C for two weeks. Xenografts provided temporary coverage before CEA transplantation. Graft take was 85%, with minor (15%) loss at 21 days, requiring small autograft coverage. At two months, the Vancouver Scar Scale score was 4, indicating optimal pigmentation, smoother texture, and minimal scarring. These findings align with limited studies on CEAs for cosmetic applications, suggesting this cost-effective technique may broaden the scope of CEAs beyond life-saving interventions to include aesthetic reconstruction, reducing both donor site morbidity and scarring. Full article

This case report presents the clinical evaluation of an 11-year-old boy with a unilateral polypoid nasal mass causing nasal obstruction, facial asymmetry, and intermittent epistaxis. His clinical picture raised concerns of a juvenile nasopharyngeal angiofibroma; however, further imaging and histopathological evaluation ultimately confirmed the diagnosis of allergic fungal rhinosinusitis (AFRS). Although this patient was younger in age than those traditionally associated with AFRS, classical features present on both computed tomography (CT) and magnetic resonance imaging (MRI) aided in his diagnosis and management. This case underscores the importance of a comprehensive diagnostic approach when evaluating unilateral sinonasal masses in paediatric patients, specifically in atypical presentations where the diagnosis of AFRS may not initially be considered. It highlights the critical role of imaging as a diagnostic tool, specifically CT and MRI, which were pivotal in the work-up and management of this case. Additionally, the need for caution during biopsies of sinonasal masses in children is emphasised, as there is potential for catastrophic bleeding in vascularised masses such as juvenile nasopharyngeal angiofibroma. This case demonstrates that AFRS can occur in younger children, highlighting the need to include this in the differential diagnosis, even in patients outside of the traditionally described age group. Full article

Background: Pulmonary tuberculosis (TB) frequently leads to long-term lung complications that contribute to increased mortality. Understanding the pathogenesis of post-TB lung impairments is crucial for improving long-term outcomes in TB patients; yet this area remains poorly researched. Methods: Our study assessed circulatory inflammatory markers in patients who completed TB treatment more than one year before enrolment (population 1) and patients receiving in-hospital treatment for active drug-sensitive TB (population 2). Results: IL-6 was seven times higher in both populations compared to the normal range. IL-8 was below the limit of detection (LOD) in population 1, while it was approximately 2.5 times higher in population 2 compared to the normal range. TNF-α was 21 times higher in population 1 and 19 times higher in population 2 compared to the normal range. CRP was almost 49 times higher in both populations, and IL-1Ra was below the LOD in population 1, while it was ~1.5 times higher in population 2 compared to the normal range. Conclusions: These inflammatory biomarkers correlated well with lung function in the post-TB state, and their high levels suggest a persistent pro-inflammatory state post-TB, which may contribute to post-TB lung disease. More research is warranted to better understand this phenomenon, but these findings may highlight a need to consider anti-inflammatory therapy for patients with post-TB lung disease, especially since these high levels of cytokines can directly contribute to lung damage. Full article

Background: Myocardial fibrosis in aortic stenosis (AS) is associated with a significant risk of poor clinical outcomes. Myocardial fibrosis can be evaluated using cardiovascular magnetic resonance (CMR) imaging and may be useful for risk-stratifying patients at high risk for poorer outcomes. A circulating biomarker of fibrosis may be a cheaper, more accessible alternative to CMR in lower-to-middle-income countries. This study evaluated the correlation between serum biomarkers of myocardial fibrosis (TGF-β1, PICP, and PIIINP) with CMR markers of myocardial fibrosis (T1 mapping, extracellular volume fraction (ECV), and late gadolinium enhancement (LGE)). Methods: Twenty-one high-gradient (mean gradient ≥ 40 mmHg) severe AS (aortic valve area < 1.0 cm²) participants underwent T1 mapping and LGE imaging using CMR. Blood serum was collected for enzyme-linked immunosorbent assays of the listed biomarkers. Results: Serum TGF-β1 was associated significantly with the global T1 relaxation time on CMR (r = 0.46 with 95% CI 0.03 to 0.74, p = 0.04). In the high T1 time group (1056 vs. 1023 ms), trends toward elevated serum TGF-β1 concentration (13,044 vs. 10,341 pg/mL, p = 0.08) and ECV (26% vs. 24%, p = 0.07) were observed. The high T1 and trend towards elevated TGF-β1 concentration in this group tracked adverse LV remodeling and systolic dysfunction. There were no significant associations between PICP/PIIINP and T1 mapping or between the biomarkers and LGE quantity. Conclusions: Serum TGF-β1 is a potential surrogate for diffuse interstitial fibrosis measured by T1 mapping and ECV on CMR. Serum PICP and PIIINP may be less appropriate as surrogate markers of fibrosis in view of their temporal trends over the course of AS. Larger studies are needed to validate the utility of TGF-β1 as a marker of diffuse fibrosis and to evaluate the utility of serial PICP/PIIINP measurements to predict decompensation. Full article

Background: Data from African neonatal units conducting bloodstream infection (BSI) surveillance is limited. Methods: Prospective clinical and laboratory surveillance of incident BSI episodes was conducted among in-patients at the 132-bed neonatal service at Tygerberg Hospital, Cape Town, South Africa (2017–2021), describing patient demographics, BSI rates, pathogen profiles, and empiric antibiotic concordance rates. Results: In total, 842 BSI episodes were identified in 740 neonates; most were preterm (661/740; 89.3%) and of low birth weight (640/740; 86.5%). The early onset BSI rate (<3 days of life) was 2.9/1000 live births, with S. agalactiae, K. pneumoniae, and E. coli predominating. Over time, ampicillin plus gentamicin coverage rates for early onset BSI pathogens declined from 93.8% to 63.6%. The healthcare-associated BSI rate (onset >3 days of life) was 3.4/1000 in-patient days, with K. pneumoniae, S. aureus, and S. marcescens predominating. Antibiotic coverage rates for healthcare-associated BSIs improved over time, from 72.2% to 89.2% (piperacillin plus amikacin) and from 68.1% to 84.6% (meropenem). Nearly one-third of BSI episodes were fatal (244/842; 29.0%), with two-thirds of these deaths considered BSI-attributable. Gram-negative BSIs increased mortality (OR 2.88; 95% CI 1.93–4.32) compared to Gram-positive BSIs (p < 0.001). Discordant empiric antibiotic therapy (OR 1.55; 95% CI 1.10–2.17) increased the risk of death compared to concordant therapy (p = 0.012). Conclusions: Neonatal BSI surveillance demonstrated that Gram-negative pathogens remain important causes of early onset and healthcare-associated BSIs in this resource-limited neonatal service. Declining coverage rates for empiric antibiotics prescribed for early onset BSI highlight the need for a change in treatment guidelines to minimise discordant therapy. Full article

Background: Despite “successful” treatment, some lung tuberculosis (TB) patients develop long-term lung impairments that includes damage to the parenchyma and reduced function, which may predispose them to diseases like pulmonary hypertension. However, this is not well understood. Therefore, we investigated whether previous or current TB patients would display elevated biomarkers of endothelial dysfunction and vascular remodeling. Methods: We performed assays for ADMA, VCAM-1, VEGF, angiopoietin-1, TBARS, NT-pro-BNP, and cardiac troponin-I. We further stratified the patients based on 1, 2, 3, and >3 previous TB episodes, and 1–5 yrs, 5–10 yrs, 10–15 yrs and >15 yrs after the last TB treatment completion. We also assessed correlations between the biomarkers and the number of previous TB episodes or the time since the completion of the last TB treatment. Results: ADMA was 70 times higher, VEGF was 2000 times higher and angiopoietin-1 was 6500 times higher than the normal range. NT-pro-BNP and cardiac troponin-I were undetected, and TBARS levels were low. There was a positive linear relationship between the number of previous TB episodes and angiopoietin-1, and between VEGF and the number of previous TB episodes. ADMA, VCAM-1 and TBARS exhibited a weak and negative linear association with the number of previous TB episodes. A negligible negative linear association was observed between the time since the completion of the last TB treatment and angiopoietin-1, VEGF and ADMA. Conclusions: Therefore, having >1 previous TB episode, despite the successful completion of TB treatment, associates with an increased risk of endothelial dysfunction/angiogenesis or vascular remodeling. Full article

Neonatal encephalopathy suspected to be due to hypoxic ischaemic encephalopathy (NESHIE) carries the risk of death or severe disability (cognitive defects and cerebral palsy). Previous genetic studies on NESHIE have predominantly focused on exomes or targeted genes. The objective of this study was to identify genetic variants associated with moderate–severe NESHIE through whole-genome, unbiased analysis. Variant filtering and prioritization were performed, followed by association testing both on a case–control basis and to compare the grades of severity and/or progression. Association testing on neonates with NESHIE (N = 172) and ancestry-matched controls (N = 288) produced 71 significant genetic variants (false discovery rate corrected p-value < 6.2 × 10⁻⁴), all located in non-coding regions and not previously implicated in NESHIE. Disease-associated variants in non-coding regions are considered to affect regulatory functions, possibly by modifying gene expression, promoters, enhancers, or DNA structure. The most significant variant was at position 6:162010973 in the Parkin RBR E3 ubiquitin protein ligase (PRKN) intron. Intronic variants were also identified in genes involved in inflammatory processes (SLCO3A1), DNA repair (ZGRF1), synaptogenesis (CNTN5), haematopoiesis (ASXL2), and the transcriptional response to hypoxia (PADI4). Ten variants were associated with a higher severity or lack of improvement in NESHIE, including one in ADAMTS3, which encodes a procollagen amino protease with a role in angiogenesis and lymphangiogenesis. This analysis represents one of the first efforts to analyze whole-genome data to investigate the genetic complexity of NESHIE in diverse ethnolinguistic groups of African origin and provides direction for further study. Full article

Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (PRLT) with Lutetium-177 ([¹⁷⁷Lu]Lu-PSMA) is a safe and effective treatment for metastatic castration-resistant prostate cancer (mCRPC). The aim of our study was to evaluate clinical variables of patients with extreme response to PRLT and to assess its immunomodulatory potential. Methods: This retrospective study included 36 patients from two centers achieving extreme response after [¹⁷⁷Lu]Lu-PSMA PRLT. The primary outcomes were the duration of maintained response in months (MR) and improvement post-therapy—clinically, serologically, and on molecular (PET/CT) imaging. We examined several variables, including pathology, gene sequencing, baseline PSA, Gleason score, prior therapies, number of PRLT cycles, and pattern of disease, to identify potential factors that may influence the extreme response. Results: Between 2018 and mid-September 2024, 36 men with mCRPC received a mean of three cycles of [¹⁷⁷Lu]Lu-PSMA PRLT. Patients were subgrouped according to clinical variables versus MR. A total of 17 patients had ≥12 months MR (17/36, 47%). The longest duration of MR was 99 months and a mean of 17.44 months (95% CI 10.05–24.84). Previous lines of treatment were evaluated for MR, p = 0.172. Pattern of disease (bone, lymph node, liver, and peritoneal) was evaluated for MR, p = 0.721. The Gleason score was evaluated for MR, p = 0.871. Patients with known BRCA sequencing status (n = 12) were analyzed with mean MR: BRCA1/2 wild-type, 6/12 (50%), 6.67 months; BRCA 1/2 negative, 1/12 (8.33%), 7 months; BRCA germline negative and somatic positive, 1/12 (8.33%), 36 months; BRCA germline negative, somatic negative, 2/12 (16.67%), 27 months; and BRCA 2 positive, 2/12 (16.67%), 43 months. Conclusions: We propose there may be intrinsic mechanisms suggesting the immunomodulatory enhancement of ionizing radiation, primarily driving extreme responses. Full article

Aortic stenosis (AS) is associated with the development of replacement myocardial fibrosis/scar. Given the dose-dependent relationship between scar and clinical outcomes after aortic valve replacement (AVR) surgery, scar quantity may serve as an important risk-stratification tool to aid decision-making on the optimal timing of AVR. Scar is non-invasively assessed and quantified by cardiovascular magnetic resonance (CMR) imaging. Several quantification techniques exist, and consensus on the optimal technique is lacking. These techniques range from a visual manual method to fully automated ones. This review describes the different scar quantification techniques used and highlights their strengths and shortfalls within the context of AS. The two most commonly used techniques in AS include the semi-automated signal threshold versus reference mean (STRM) and full-width half-maximum (FWHM) techniques. The accuracy and reproducibility of these techniques may be hindered in AS by the coexistence of diffuse interstitial fibrosis and the presence of relatively small, non-bright scars. The validation of these techniques against histology, which is the current gold standard for scar quantification in AS, is limited. Based on the best current evidence, the STRM method using a threshold of three standard deviations above the mean signal intensity of remote myocardium is recommended. The high reproducibility of the FWHM technique in non-AS cohorts has been shown and merits further evaluation within the context of AS. Future directions include the use of quantitative T1 mapping for the detection and quantification of scar, as well as the development of serum biomarkers that reflect the fibrotic status of the myocardium in AS. Full article

Background: Temporomandibular disorders (TMD) affect a significant portion of the population, with profound psychological, behavioral, and social repercussions. Recent investigations have explored the genetic basis underlying pain perception in individuals with TMD, aiming to elucidate the role of specific genetic factors in modulating the condition. Notably, genetic variations have been implicated in the pathogenesis of TMD, particularly genes involved in pain perception pathways. One of the primary candidates is the Catechol-O-Methyltransferase (COMT) gene, which plays a crucial role in the catecholaminergic system and has been associated with the regulation of nociceptive processes. This study seeks to investigate the correlation between COMT gene activity and pain perception among South African patients diagnosed with varying forms of TMD. Methodology: In this study, a total of 196 participants were enrolled, comprising 97 patients diagnosed with TMD and 99 control participants. The control group was meticulously matched with the TMD group for age, gender, and ethnicity. Data collection involved clinical and radiological investigations, and saliva sampling. The English version of the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) Axis I was utilized to evaluate all TMD participants, focusing on standard diagnostic measures based on clinical signs and symptoms of TMD, which primarily describe common physical manifestations of the disorder. Genomic DNA was extracted from saliva samples, enabling the analysis of single-nucleotide polymorphisms (SNPs) in the COMT gene, specifically targeting polymorphisms rs165774, rs9332377, rs6269, rs4646310, rs165656, and rs4680. Results: The current study demonstrated a pronounced gender disparity, with 80.41% of the participants being female and 19.59% male, suggesting that women in South Africa either exhibit a higher susceptibility to TMD or are more likely to seek treatment for the condition compared to men. The highest prevalence of TMD was observed in the white population (58.76%). Additionally, over 65% of TMD patients were diagnosed with at least two Axis I diagnoses, a figure that increased to 89% for those diagnosed with three Axis I diagnoses. The findings further indicated significant associations between several single-nucleotide polymorphisms (SNPs) in the Catechol-O-Methyltransferase (COMT) gene—specifically rs165656, rs9332377, rs4646310, rs6269, and rs165774—and both TMD and TMD-related pain. Myofascial pain with referral and myalgia showed a strong association with the COMT SNPs rs9332377 and rs4646310. Furthermore, COMT SNP rs4646310 was also associated with disability related to TMD. Conclusions: This study substantiates the hypothesis that pain is prevalent in a considerable proportion of patients affected by TMD. Furthermore, the findings reveal a significant association between COMT gene activity and pain perception in South African patients diagnosed with TMD. Full article

Maternal nutritional status during pregnancy affects the growth of the foetus and may impair the development of different organs, some of which may affect cardio-metabolic health in early childhood. This study determined the dietary intake of pregnant women and its possible associations with early child cardio-metabolic risk. Methods: Dietary data were collected from 152 of a larger sample of 500 pregnant women and their children at birth and at the age of 5–6 years within the Tygerberg Academic Hospital catchment area, Bellville, South Africa. Maternal weight, height, BMI and mid-upper arm circumference were collected at recruitment. Birth weight, length, head circumference and placental weight were collected at birth. At the age of 5–6 years, anthropometric measurements (weight, height, skinfold thickness and waist circumference), clinical measurements (blood pressure, mean arterial pressure and heart rate) and ultrasound measurements (pancreas, aorta, carotid arteries and visceral fat) were collected. For the purpose of this abstract, we will report only on the ultrasound measurements for vascular and pancreas parameters. Dietary data were collected using a quantified food frequency questionnaire. Results: Iron intake did not differ significantly between the trimesters, nor between mothers who smoked (14.5 mg), consumed alcohol (16.5 mg) or both (15.0 mg). The average total energy intake of mothers was 10,850 kJ (SD = 3001 kJ), which was slightly above NIH recommendations. Most of the energy came in the form of saturated fat, oils and added sugar. Both protein and carbohydrate intake exceeded recommendations, with average intakes of 82 g and 275 g, respectively. Folate intake was below recommendations at 287 mcg. A significant association was found between maternal carbohydrate intake and the size of the pancreas body (0.164; p < 0.05) as well as between protein intake and aorta intima media thickness (r = 0.201; p < 0.05), while a negative association was found between polyunsaturated fat intake and left carotid intima media thickness (−0.179; p < 0.05). Conclusions: Dietary intake in this group did not indicate nutritional deficiencies. However, the low folate intake may be of concern. The association of fats with vascular wall thickness and the association of carbohydrate intake with increased pancreas size needs further investigation. Full article

Community genetic services were introduced in South Africa almost seven decades ago, with medical geneticists and genetic counsellors being formally recognized for the past 30 years. Initial training platforms were established at academic centres countrywide, and posts for relevant healthcare professionals, including medical geneticists and genetic counsellors were created in the public sector. Despite these early advances, the number of these specialists required to address the rising burden of congenital disorders in the country remains far below required targets established by the National Department of Health. The aim of this study was to analyse the retrospective, current and projected number of medical geneticists and genetic counsellors in South Africa. The results indicate the number of practicing medical geneticists (n = 13) and genetic counsellors (n = 28) are currently at 10% and 5% of capacity targets, respectively. There is unequal distribution of these specialists between the public and private healthcare sectors, and geographical maldistribution. An alarming trend of emigration is particularly prevalent among newly qualified genetic counsellors. With the proportion of congenital disorders expected to continue to rise in coming years, together with the increasing proportion of ageing South Africans, it is imperative that health workforce planning addresses the ever-widening gap between the supply, demand and unmet need for these crucial specialists in South Africa. Full article

Objectives: There is a paucity of data on the outcome of left-sided cardiac valve surgery for infective endocarditis in South Africa. It is hypothesized that outcomes may be poorer compared to international standards due to differences in disease burden, timing of surgery, organism prevalence, and co-morbidities. Method: This is a retrospective study of 160 patients with left heart valve endocarditis who underwent cardiac surgery from January 2010 to December 2019. Demographic, operative, and admission-related parameters were assessed to determine their association with all-cause mortality during the early post-operative (<30 days) and late post-operative (>30 days) periods. Results: Early post-operative mortality (<30 days) was 8.8% and late post-operative mortality (>30 days) was 13.1%. Late survival showed 77.5% of the patients were alive with a mean follow-up period of 41 months. Increased age (p = 0.04), critical illness (p < 0.001), and higher urgency of intervention (p < 0.001) were associated with higher early post-operative mortality. Peri-operative organ failure, including cardiac (p = 0.025), renal (p = 0.016), and respiratory failure (p < 0.001), contributed significantly to both early and late mortality. Pre-operative antibiotics for fewer days (p = 0.024), ongoing sepsis (p = 0.022), and para-valvular extension (p = 0.046) were associated with higher early mortality. Conclusions: Infective endocarditis is a common indication for cardiac valve surgery in South Africa. Goal-directed medical management and clinical optimization prior to surgery were crucial to achieving better outcomes. Salvage procedures and critical illness with organ failure prior to surgery were associated with poorer outcomes. Despite unique challenges, cardiac surgery for infective endocarditis at Tygerberg Hospital compares favorably to international standards. Full article

Background: Previous research has shown that the Serum Amyloid A (SAA) protein family is intricately involved in inflammatory signaling and various disease pathologies. We have previously demonstrated that SAA is associated with increased colitis disease severity and the promotion of tumorigenesis. However, the specific role of SAA proteins in breast cancer pathology remains unclear. Therefore, we investigated the role of systemic SAA1 and SAA2 (SAA1/2) in a triple-negative breast cancer mouse model. Methods: Syngeneic breast tumors were established in wild-type mice, and mice lacking the SAA1/2 (SAADKO). Subsequently, tumor volume was monitored, species survival determined, the inflammatory profiles of mice assessed with a multiplex assay, and tumor molecular biology and histology characterized with Western blotting and H&E histological staining. Results: WT tumor-bearing mice had increased levels of plasma SAA compared to wild-type control mice, while SAADKO control and tumor-bearing mice presented with lower levels of SAA in their plasma. SAADKO tumor-bearing mice also displayed significantly lower concentrations of systemic inflammatory markers. Tumors from SAADKO mice overall had lower levels of SAA compared to tumors from wild-type mice, decreased apoptosis and inflammasome signaling, and little to no tumor necrosis. Conclusions: We demonstrated that systemic SAA1/2 stimulates the activation of the NLRP3 inflammasome in breast tumors, leading to the production of pro-inflammatory cytokines. This, in turn, promoted apoptosis and tumor necrosis but did not significantly impact tumor growth or histological grading. Full article

Diarrhoeagenic E. coli (DEC) significantly contributes to the burden of diarrhoea among children. Currently, there is no approved vaccine against DEC, but several vaccines against the enterotoxigenic E. coli (ETEC) pathotype are in advanced clinical trial stages, including the ETVAX^® vaccine, undergoing evaluation in Zambia. This study reports on the reactivity of antibodies from ETVAX^® vaccine and placebo recipients in a phase I clinical trial to proteins derived from (DEC) other than ETEC. Plasma samples collected at two time points (prior to any vaccination and post-third dose vaccination) from 16 vaccinated and 4 placebo participants in a phase 1 clinical trial examining the safety, tolerability, and immunogenicity of ETVAX^® with dmLT adjuvant were evaluated for IgG response to E. coli antigens other than ETEC using the Pan-DEC protein microarray. This was the first field application of the novel pan-DEC array as a new tool in assessing the antigenic breadth of antibody responses induced by the ETVAX vaccine, as well as to assess early life exposure to DEC pathotypes and other bacterial enteric pathogens. We observed that plasma obtained from ETVAX^® and placebo recipients had high antibody reactivity to Ipa, SseC and EspB proteins. These findings suggest that there is high exposure early in life to DEC pathogens, like EPEC, EHEC, EAEC and EIEC in addition to ETEC, in the Zambian population. These immunological observations are consistent with the results of recent epidemiological studies assessing the etiology of diarrheal disease among infants and young children in Zambia. Full article