Background Current tuberculosis treatments leave patients with clinically significant lung injury and increased allcause mortality post-cure. Adjunctive host-directed therapies could protect the lungs, improve long-term survival, and shorten treatment duration; however, few have been tested clinically. Therefore, we aimed to assess the safety and preliminary efficacy of four host-directed therapies for tuberculosis.Methods In this prospective, open-label, phase 2, randomised controlled trial, patients with pulmonary tuberculosis were recruited at three clinical sites in South Africa. Eligible patients were aged 18-65 years, HIV-1-negative, and had rifampicin-susceptible Mycobacterium tuberculosis, a sputum Xpert cycle threshold of less than 20, and moderately advanced or far advanced disease on chest radiography. By use of numbers generated in blocks of ten and stratification by site, eligible patients were randomly assigned (1:1:1:1:1) to receive one of the four oral host-directed treatments plus standard tuberculosis treatment or standard treatment alone (the control group). Host-directed treatments were: CC-11050 (200 mg twice daily, taken with food; day 1-112); everolimus (0•5 mg/day; day 1-112); auranofin (3 mg/day for seven doses, then 6 mg/day; day 1-112); and ergocalciferol (5 mg on day 1, then 2•5 mg on day 28 and day 56). All study participants received oral rifabutin-substituted standard tuberculosis treatment for 180 days. Patients and clinicians were not masked to treatment assignment. Spirometry and sputum culture with solid and liquid media were done at baseline and up to 180 days at specified intervals throughout treatment. The primary endpoint was safety and tolerability up to day 210. Secondary preliminary efficacy endpoints were treatment effects on sputum microbiology (culture status at day 56 and the hazard ratio for stable culture conversion up to day 180) and lung function (FEV 1 and forced vital capacity [FVC]) measured by spirometry at day 56, day 180, and day 540. Safety was analysed in the intention-to-treat population and preliminary efficacy primarily in the per-protocol population. The trial is registered at ClinicalTrials.gov, NCT02968927. Post-treatment follow-up was completed in 2020.

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Background While tuberculosis is considered a risk factor for chronic obstructive pulmonary disease, a restrictive pattern of pulmonary impairment may actually be more common among tuberculosis survivors. We aimed to determine the nature of pulmonary impairment before and after treatment among people with HIV and tuberculosis and identify risk factors for long-term impairment. Methods In this prospective cohort study conducted in South Africa, we enrolled adults newly diagnosed with HIV and tuberculosis who were initiating antiretroviral therapy and tuberculosis treatment. We measured lung function and symptoms at baseline, 6, and 12 months. We compared participants with and without pulmonary impairment and constructed logistic regression models to identify characteristics associated with pulmonary impairment. Results Among 134 participants with a median CD4 count of 110 cells/μl, 112 (83%) completed baseline spirometry at which time 32 (29%) had restriction, 13 (12%) had obstruction, and 9 (7%) had a mixed pattern. Lung function was dynamic over time and 30 (33%) participants had impaired lung function at 12 months. Baseline restriction was associated with greater symptoms and with long-term pulmonary impairment (adjusted odds ratio 5.44, 95% confidence interval 1.16–25.45), while baseline obstruction was not (adjusted odds ratio 1.95, 95% confidence interval 0.28–13.78). Conclusions In this cohort of people with HIV and tuberculosis, restriction was the most common, symptomatic, and persistent pattern of pulmonary impairment. These data can help to raise awareness among clinicians about the heterogeneity of post-tuberculosis pulmonary impairment, and highlight the need for further research into mediators of lung injury in this vulnerable population.

Background: Prostate cancer is an important cause of morbidity and mortality in South Africa, as it is in the rest of the world. In African men, however, prostate cancer tends to follow a more aggressive course when compared to their European counterparts. This is attributed to a plethora of diverse factors of which an underlying genetic component has been shown to be an important aspect. Such differences highlight the need for individualised therapy and for local guidelines. The aim of this guideline is to aid nuclear physicians and other clinicians who manage patients with prostate cancer in the correct identification and treatment of patients who are likely to benefit from receptor radioligand therapy. Recommendations: There are a multitude of treatment modalities available for the treatment of prostate cancer and these therapies may be required at various time points during the course of the disease in any individual patient. A multidisciplinary approach is crucial in deciding which therapy, or combination of therapies, would be most advantageous at particular time points. The multidisciplinary team should include a urologist, oncologist and nuclear medicine physician as a minimum, and should ideally also involve a palliative/pain specialist, a dietician and a psychologist. Conclusion: Treatment with 177 Lu-PSMA has emerged as a promising systemic modality, which involves the delivery of targeted radiation therapy in the form of β-particles to sites of tumour tissue. Therapy is provided on an outpatient basis, is well tolerated with relatively few side effects and has a positive effect on overall survival and quality of life. At present, it is used mostly in the setting of advanced, castrate-resistant cancer. Patients are selected (amongst other criteria) based on the prior PSMA-based SPECT/PET/CT imaging ( 99m Tc-, 68 Ga-or 18 F-PSMA), which should demonstrate sufficient receptor expression in order to consider PSMA-based targeted radionuclide therapy. Such imaging of an intended target prior to its therapeutic targeting is known as a theranostic approach.