Tygerberg Hospital

Abstract Background Retinoblastoma (Rb) is the most common childhood intraocular cancer, with heritable forms caused by pathogenic germline variants in the RB1 (or retinoblastoma 1) gene, which necessitate intensive and costly lifelong surveillance. Genetic testing enables precise risk prediction and individualized clinical management, yet data on the RB1 variant spectrum in African populations remains scarce. This study investigated the molecular landscape of clinically presumed heritable Rb in a Southern African cohort and evaluated the potential healthcare and economic benefits of implementing genetic testing. Methods Fifty-eight patients with clinically presumed heritable Rb were recruited from two tertiary hospitals in South Africa. Comprehensive RB1 gene analysis was performed using next-generation sequencing (NGS) to detect single nucleotide variants (SNVs), small insertions and deletions (indels), and copy number variants (CNVs), and was supplemented by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). A cost comparison model was developed to evaluate conventional clinical screening versus a genetically guided approach. Results RB1 pathogenic and/or likely pathogenic variants were identified in 84.5% (49/58) of patients, including eleven novel variants. The variant spectrum included frameshift, nonsense, splicing, intronic, and missense changes, with a notable concentration in the pocket domain region of the Rb associated protein (pRb). CNVs were detected in 10.3% of probands. Our cost analysis demonstrated significant savings associated with genetic testing, reducing surveillance-related expenses by up to US$228,989 across extended family generations in the private sector and US$166,489 in the public sector. Implementing genetic testing would also minimize unnecessary examinations and promote more efficient allocation of healthcare resources. Conclusions Comprehensive RB1 genetic testing in this Southern African cohort revealed a diverse variant landscape, including novel pathogenic changes, and demonstrated the clinical and economic value of integrating genetic testing into Rb management. These findings contribute to the global understanding of genetic variation within the RB1 gene and support tailored care strategies that can reduce the surveillance burden, optimize healthcare resources, and improve outcomes for affected families.

Depression in pregnancy is associated with adverse outcomes for both mother and baby. Estimates of the prevalence of depression in pregnancy vary considerably across low- and middle-income countries. We set out to prospectively determine the prevalence of depression in pregnancy in two low- and middle-income countries, and to investigate its association with adverse pregnancy outcomes. This multinational prospective cohort study was conducted in Pakistan and South Africa from 2021 to 2023 in two tertiary referral centres. The Edinburgh Postnatal Depression Scale was administered to women between 20- and 34- weeks' gestation. Women were followed up and pregnancy outcomes collected. A Bayesian model accounting for the sensitivity and specificity of the Edinburgh Postnatal Depression Scale was used to estimate prevalence. 1537 participants were recruited. The adjusted prevalence of depression in pregnancy was 17.1% (95% credible interval [CrI] 13.3% - 21.1%). Estimates varied across sites, in Pakistan, 10.8% (95% CrI 7.7% - 14.3%), and in South Africa, 25.9% (95% Crl 20.8% - 31.1%) of women experienced depression in pregnancy. There were no associations between screening positive on the Edinburgh Postnatal Depression Scale (score≥11) and spontaneous preterm birth (adjusted odds ratio [aOR] 1.20 95% confidence interval [CI] 0.79-1.83), low birthweight (aOR 1.25 95% CI 0.91-1.72), or admission to a special care/neonatal intensive care unit (aOR 0.95 95% CI 0.59-1.52). Within our study cohort, spanning two centres in Pakistan and South Africa, one in six women experienced depression in pregnancy. Reassuringly, depression was not associated with an increase in adverse pregnancy outcomes; spontaneous preterm birth, low birthweight or admission to neonatal intensive care/special care nursery. Our study provides robust estimates of the burden of depression in pregnancy in two low- and middle-income countries; an important first step in addressing maternal mental health.

Increased risk of infectious morbidity and hospitalization has been reported during infancy among children HIV-exposed uninfected (CHEU) compared to children HIV-unexposed uninfected (CHUU). However, data on risks beyond infancy are limited. We enrolled pregnant women with and without HIV from a primary healthcare facility in a lower income area in Cape Town, South Africa (2017-2018). We tracked their children's HIV test results and hospitalizations using routine electronic healthcare data. We previously reported increased rates of infectious-cause hospitalization among CHEU in the first year of life, and now extend the analysis to cover the period from age 1 to less than 5 years. Using random-effects Poisson regression, we calculated adjusted incidence rate ratios (aIRR) for infectious-cause hospitalization among CHEU vs. CHUU, clustered by infant and adjusted for child sex and vaccination status, maternal age and education, and housing type. Among 446 CHEU and 455 CHUU, 147 admissions occurred from age 1 to less than 5 years; with 59% ( n = 87) due to infections. All-cause hospitalization occurred in 9.2% of CHEU and 10.5% of CHUU; infectious-cause hospitalization occurred in 6.5% of CHEU and 7.3% of CHUU with crude incidence rates of 2.4 per 100 child-years for both groups [IRR = 1.0; 95% confidence interval (CI) 0.6-1.6]. Adjusted analyses showed no evidence of increased hospitalization among CHEU (aIRR = 0.71; 95% CI 0.36-1.41). Elevated risk of infectious-cause hospitalization among CHEU did not persist beyond the first year of life. These findings highlight infancy as a key window for targeted interventions, while providing reassurance regarding longer term infectious morbidity risk.

Diaphyseal non-union of forearm fractures that involve both the ulna and radius present unique challenges to treat. If left untreated, these non-unions may lead to severe instability of the forearm and/or chronic pain. Existing treatments include bone grafting, fibular grafts, and the Masquelet technique, however, currently no gold standard treatment exists. The “Road-to-Union” protocol is a two-stage surgical approach originally developed for managing complex tibial bone defects. It integrates debridement, circular external fixation, soft-tissue management, distraction osteogenesis, and structured rehabilitation. This technique addresses challenges such as infection, bone loss, and deformity by providing a systematic pathway to achieve bone healing and restore function. While traditionally used in the lower limb, its application in the forearm has not been widely reported. This case series explores the adaptation of the “Road-to-Union” protocol for forearm reconstruction, aiming to restore structural integrity and function in complex non-union cases.

BackgroundIn most healthy adults, respiratory syncytial virus (RSV) causes mild self-limiting respiratory infection. However, vulnerable populations may present differently or have more complicated courses of disease.ObjectivesTo describe the clinical and radiographic features of adults hospitalised with RSV-associated severe respiratory illness (SRI) in two urban hospitals during 2022 and 2023.MethodsPatients aged ≥18 years were enrolled through systematic sentinel surveillance for SRI. Clinical characteristics and radiographic profiles of RSV-infected adults were reviewed.ResultsEighteen (2%) of 916 enrolled hospitalised patients with SRI tested positive for RSV at the two hospitals. Other pathogens detected included SARS-CoV-2 (n=69/916; 8%), influenza (n=49/916; 5%) and pertussis (n=10/916; 1%). The median (range) age was 50 (35 - 75) years, and 12 (67%) were female. All had at least one comorbidity, including immunocompromising conditions (n=15/18; 83%), metabolic conditions (n=8/18; 44%), structural lung disease (n=12/18; 66%) and cardiovascular conditions (n=3/18; 16%). Among persons living with HIV (n=11/18; 61%), 72% (n=8/11) had suppressed HIV viral loads, and 9/11 (81%) had CD4 counts <250 cells/µL. Median (range) length of hospital stay was 4.5 (1 - 15) days. All patients received empirical antibiotics, intravenously in 12/18 (66%); only 5/12 (41%) de-escalated to oral antibiotics. Radiographic findings demonstrated post-tuberculosis lung disease (PTLD) in 50% of patients (n=9/18), of whom 11 (61%) had new ground-glass opacifications, with lobar v. diffuse in 55% (n=6/11) v. 45% (n=5/11).ConclusionThe high prevalence of underlying conditions in adults with RSV-associated SRI, specifically HIV and PTLD, suggests that targeted vaccination in these groups may prevent hospitalisation with RSV-associated SRI.Study synopsisWhat the study adds. This study identified a distinct clinical and radiographic profile of adults hospitalised with respiratory syncytial virus (RSV)-associated severe respiratory illness in South Africa, where HIV infection, post-tuberculosis lung disease (PTLD) and polysubstanceinduced lung damage were the predominant comorbidities, unlike traditional cardiometabolic risk profiles seen elsewhere. It also found characteristic chest radiographic features such as lobar and diffuse ground-glass opacifications in these patients.Implications of the findings. The findings suggest the need to expand RSV vaccination recommendation protocols to include younger adults with HIV and PTLD. They also highlight the importance of improving antimicrobial stewardship and developing better diagnostic tools to differentiate viral from bacterial infections. These findings are crucial in our high burden of disease setting.