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Introduction The outbreak of the SARS-CoV-2 virus causing COVID-19, declared a global pandemic by the WHO, is a novel infection with a high rate of morbidity and mortality. In South Africa, 55 421 cases have been confirmed as of 10 June 2020, with most cases in the Western Cape Province. Coronavirus leaves us in a position of uncertainty regarding the best clinical approach to successfully manage the expected high number of severely ill patients with COVID-19. This presents a unique opportunity to gather data to inform best practices in clinical approach and public health interventions to control COVID-19 locally. Furthermore, this pandemic challenges our resolve due to the high burden of HIV and tuberculosis (TB) in our country as data are scarce. This study endeavours to determine the clinical presentation, severity and prognosis of patients with COVID-19 admitted to our hospital. Methods and analysis The study will use multiple approaches taking into account the evolving nature of the COVID-19 pandemic. Prospective observational design to describe specific patterns of risk predictors of poor outcomes among patients with severe COVID-19 admitted to Tygerberg Hospital. Data will be collected from medical records of patients with severe COVID-19 admitted at Tygerberg Hospital. Using the Cox proportional hazards model, we will investigate the association between the survival time of patients with COVID-19 in relation to one or more of the predictor variables including HIV and TB. Ethics and dissemination The research team obtained ethical approval from the Health Research Ethics Committee of the Faculty of Medicine and Health Sciences, Stellenbosch University and Research Committee of the Tygerberg Hospital. All procedures for the ethical conduct of scientific investigation will be adhered to by the research team. The findings will be disseminated in clinical seminars, scientific forums and conferences targeting clinical care providers and policy-makers. [ABSTRACT FROM AUTHOR]

Background: The potentially curative and/or palliative therapy for non‐resectable lung cancer has evolved significantly over the past 2 decades. With the availability of targeted therapies, the need for precise sub‐typing of non‐small cell lung carcinoma (NCSLC) has become paramount. Objectives: As there are few data from South Africa, we aimed to determine utility of TTF‐1, napsin A, p63 and CK5 immunostaining on fine needle aspiration (FNA) cell block and formalin‐fixed paraffin‐embedded tissue biopsy specimens in subtyping NSCLC as adenocarcinoma and squamous cell carcinomas. Methods: All cases of NSCLC diagnosed during a 3‐year period were retrospectively identified. All FNA biopsy and formalin‐fixed paraffin‐embedded cases that were stained with TTF‐1, napsin A, CK5 and p63 were collected. A lung cancer registry was used to access and correlate clinical and radiological data. Results: We included 271 cases with diagnoses of adenocarcinoma of the lung (n = 201), squamous cell carcinoma of the lung (n = 53), unspecified NSCLC (n = 8) and other carcinomas (n = 9). TTF‐1 and napsin A had sensitivities of 99.0% and 91.9%, respectively, positive predictive values (PPVs) of 90.8% and 90.3%, respectively, and accuracies of 91.0% for adenocarcinoma of the lung. Napsin A had a higher specificity than TTF‐1 (90.2% vs 62.8%). Both CK5 and P63 had high sensitivities (95.4% and 97.9%, respectively) and negative predictive values of 96.4% and 96.8%, respectively, for squamous cell carcinoma of the lung. CK5 had a higher specificity than p63 (84.4% and 61.2%, respectively), PPV (80.4% and 70.8%, respectively) and accuracy (88.8% and 79.2%, respectively) for squamous cell carcinoma. Conclusion: All four immunostaining methods had high sensitivities. TTF‐1 and napsin A both had high PPV and diagnostic accuracy for adenocarcinoma of the lung, whereas CK5 had an equally high PPV and accuracy for squamous cell carcinoma of the lung. The specificity of napsin A for adenocarcinoma was higher than that of TTF‐1. The specificity of CK5 for squamous cell carcinoma was higher than p63. Utility of TTF‐1, NapsinA, Ck5 and p63 in distinguishing between Adenocacinoma and Squamous cell carcinoma, using fine needle aspiration cellblock material and paraffin embedded biopsy specimens in a resource limited setting. [ABSTRACT FROM AUTHOR]

Background: Chylothorax is an uncommon medical condition for which limited data are available regarding the contemporary aetiology, management and outcomes. The goal of this study was to better define these poorly characterised features., Methods: The medical records of adult patients diagnosed with chylothorax at 12 centres across Europe, America and South Africa from 2009-2021 were retrospectively reviewed. Descriptive and inferential statistics were performed., Results: 77 patients (median age 69 years, male to female ratio 1.5) were included. Subacute dyspnoea was the most typical presenting symptom (66%). The commonest cause of chylothorax was malignancy (68.8%), with lymphoma accounting for 62% of these cases. Other aetiologies were trauma (13%), inflammatory/miscellaneous conditions (11.7%) and idiopathic cases (6.5%). At the initial thoracentesis, the pleural fluid appeared milky in 73%, was exudative in 89% and exhibited triglyceride concentrations >100 mg·dL -1 in 88%. Lymphangiography/lymphoscintigraphy were rarely ordered (3%), and demonstration of chylomicrons in pleural fluid was never ascertained. 67% of patients required interventional pleural procedures. Dietary measures were infrequently followed (36%). No patient underwent thoracic duct ligation or embolisation. Morbidity included infections (18%), and thrombosis in malignant aetiologies (16%). The 1-year mortality was 47%. Pleural fluid protein >3.5 mg·dL -1 (sub-distribution hazard ratio (SHR) 4.346) or lactate dehydrogenase <500 U·L -1 (SHR 10.21) increased the likelihood of effusion resolution. Pleural fluid protein ≤3.5 mg·dL -1 (HR 4.047), bilateral effusions (HR 2.749) and a history of respiratory disease (HR 2.428) negatively influenced survival., Conclusion: Chylothoraces have a poor prognosis and most require pleural interventions. Despite the standard recommendations, lymphatic imaging is seldom used, nor are dietary restrictions followed., Competing Interests: Conflict of interest: J.M. Porcel has received consultancy fees from Becton Dickinson and Suministros Hospitalarios SA (SH Medical Group), and is an associate editor of this journal. Conflict of interest: The remaining authors declare that they have no relevant conflicts of interest., (Copyright ©The authors 2023.)

Introduction: We present findings from the International Collaborative Effusion database, a European Respiratory Society clinical research collaboration. Nonspecific pleuritis (NSP) is a broad term that describes chronic pleural inflammation. Various aetiologies lead to NSP, which poses a diagnostic challenge for clinicians. A significant proportion of patients with this finding eventually develop a malignant diagnosis., Methods: 12 sites across nine countries contributed anonymised data on 187 patients. 175 records were suitable for analysis., Results: The commonest aetiology for NSP was recorded as idiopathic (80 out of 175, 44%). This was followed by pleural infection (15%), benign asbestos disease (12%), malignancy (6%) and cardiac failure (6%). The malignant diagnoses were predominantly mesothelioma (six out of 175, 3.4%) and lung adenocarcinoma (four out of 175, 2.3%). The median time to malignant diagnosis was 12.2 months (range 0.8-32 months). There was a signal towards greater asbestos exposure in the malignant NSP group compared to the benign group (0.63 versus 0.27, p=0.07). Neither recurrence of effusion requiring further therapeutic intervention nor initial biopsy approach were associated with a false-negative biopsy. A computed tomography finding of a mass lesion was the only imaging feature to demonstrate a significant association (0.18 versus 0.01, p=0.02), although sonographic pleural thickening also suggested an association (0.27 versus 0.09, p=0.09)., Discussion: This is the first multicentre study of NSP and its associated outcomes. While some of our findings are reflected by the established body of literature, other findings have highlighted important areas for future research, not previously studied in NSP., Competing Interests: Conflict of interest: J.M. Porcel is an associate editor of this journal. C.F.N. Koegelenberg declares honoraria for lectures from AstraZeneca and GlaxoSmithKline, in the 36 months prior to manuscript submission. All other authors declare no competing interests., (Copyright ©The authors 2023.)

After the results of two large, randomized trials, the global implementation of lung cancer screening is of utmost importance. However, coronavirus disease 2019 infections occurring at heightened levels during the current global pandemic and also other respiratory infections can influence scan interpretation and screening safety and uptake. Several respiratory infections can lead to lesions that mimic malignant nodules and other imaging changes suggesting malignancy, leading to an increased level of follow-up procedures or even invasive diagnostic procedures. In periods of increased rates of respiratory infections from severe acute respiratory syndrome coronavirus 2 and others, there is also a risk of transmission of these infections to the health care providers, the screenees, and patients. This became evident with the severe acute respiratory syndrome coronavirus 2 pandemic that led to a temporary global stoppage of lung cancer and other cancer screening programs. Data on the optimal management of these situations are not available. The pandemic is still ongoing and further periods of increased respiratory infections will come, in which practical guidance would be helpful. The aims of this report were: (1) to summarize the data available for possible false-positive results owing to respiratory infections; (2) to evaluate the safety concerns for screening during times of increased respiratory infections, especially during a regional outbreak or an epidemic or pandemic event; (3) to provide guidance on these situations; and (4) to stimulate research and discussions about these scenarios., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

New tuberculosis (TB) diagnostics are at a crossroads: their development, evaluation, and implementation is severely damaged by resource diversion due to COVID-19. Yet several technologies, especially those with potential for non-invasive non-sputum-based testing, hold promise for efficiently triaging and rapidly confirming TB near point-of-care. Such tests are, however, progressing through the pipeline slowly and will take years to reach patients and health workers. Compellingly, such tests will create new opportunities for difficult-to-diagnose populations, including primary care attendees (all-comers in high burden settings irrespective of reason for presentation) and community members (with early stage disease or risk factors like HIV), many of whom cannot easily produce sputum. Critically, all upcoming technologies have limitations that implementers and health workers need to be cognizant of to ensure optimal deployment without undermining confidence in a technology that still offers improvements over the status quo. In this state-of-the-art review, we critically appraise such technologies for active pulmonary TB diagnosis. We highlight strengths, limitations, outstanding research questions, and how current and future tests could be used in the presence of these limitations and uncertainties. Among triage tests, CRP (for which commercial near point-of-care devices exist) and computer-aided detection software with digital chest X-ray hold promise, together with late-stage blood-based assays that detect host and/or microbial biomarkers; however, aside from a handful of prototypes, the latter category has a shortage of promising late-stage alternatives. Furthermore, positive results from new triage tests may have utility in people without TB; however, their utility for informing diagnostic pathways for other diseases is under-researched (most sick people tested for TB do not have TB). For confirmatory tests, few true point-of-care options will be available soon; however, combining novel approaches like tongue swabs with established tests like Ultra have short-term promise but first require optimizations to specimen collection and processing procedures. Concerningly, no technologies yet have compelling evidence of meeting the World Health Organization optimal target product profile performance criteria, especially for important operational criteria crucial for field deployment. This is alarming as the target product profile criteria are themselves almost a decade old and require urgent revision, especially to cater for technologies made prominent by the COVID-19 diagnostic response (e.g., at-home testing and connectivity solutions). Throughout the review, we underscore the importance of how target populations and settings affect test performance and how the criteria by which these tests should be judged vary by use case, including in active case finding. Lastly, we advocate for health workers and researchers to themselves be vocal proponents of the uptake of both new tests and those - already available tests that remain suboptimally utilized., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Pleural tuberculosis (TB) is common and often follows a benign course but may result in serious long-term morbidity. Diagnosis is challenging because of the paucibacillary nature of the condition. Advances in Mycobacterium culture media and PCR-based techniques have increased the yield from mycobacteriologic tests. Surrogate biomarkers perform well in diagnostic accuracy studies but must be interpreted in the context of the pretest probability in the individual patient. Confirming the diagnosis often requires biopsy, which may be acquired through thoracoscopy or image-guided closed pleural biopsy. Treatment is standard anti-TB therapy, with optional drainage and intrapleural fibrinolytics or surgery in complicated cases., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The utility of heated and humidified high-flow nasal oxygen (HFNO) for severe COVID-19-related hypoxaemic respiratory failure (HRF), particularly in settings with limited access to intensive care unit (ICU) resources, remains unclear, and predictors of outcome have been poorly studied., Methods: We included consecutive patients with COVID-19-related HRF treated with HFNO at two tertiary hospitals in Cape Town, South Africa. The primary outcome was the proportion of patients who were successfully weaned from HFNO, whilst failure comprised intubation or death on HFNO., Findings: The median (IQR) arterial oxygen partial pressure to fraction inspired oxygen ratio (P a O2/FiO 2 ) was 68 (54-92) in 293 enroled patients. Of these, 137/293 (47%) of patients [P a O2/FiO 2 76 (63-93)] were successfully weaned from HFNO. The median duration of HFNO was 6 (3-9) in those successfully treated versus 2 (1-5) days in those who failed ( p <0.001). A higher ratio of oxygen saturation/FiO2 to respiratory rate within 6 h (ROX-6 score) after HFNO commencement was associated with HFNO success (ROX-6; AHR 0.43, 0.31-0.60), as was use of steroids (AHR 0.35, 95%CI 0.19-0.64). A ROX-6 score of ≥3.7 was 80% predictive of successful weaning whilst ROX-6 ≤ 2.2 was 74% predictive of failure. In total, 139 patents (52%) survived to hospital discharge, whilst mortality amongst HFNO failures with outcomes was 129/140 (92%)., Interpretation: In a resource-constrained setting, HFNO for severe COVID-19 HRF is feasible and more almost half of those who receive it can be successfully weaned without the need for mechanical ventilation., Competing Interests: BA has received speakers fees from Novartis, and CK has served on an advisory board from AstraZeneca, both outside the submitted work., (© 2020 The Author(s).)

Background: The potentially curative and/or palliative therapy for non-resectable lung cancer has evolved significantly over the past 2 decades. With the availability of targeted therapies, the need for precise sub-typing of non-small cell lung carcinoma (NCSLC) has become paramount., Objectives: As there are few data from South Africa, we aimed to determine utility of TTF-1, napsin A, p63 and CK5 immunostaining on fine needle aspiration (FNA) cell block and formalin-fixed paraffin-embedded tissue biopsy specimens in subtyping NSCLC as adenocarcinoma and squamous cell carcinomas., Methods: All cases of NSCLC diagnosed during a 3-year period were retrospectively identified. All FNA biopsy and formalin-fixed paraffin-embedded cases that were stained with TTF-1, napsin A, CK5 and p63 were collected. A lung cancer registry was used to access and correlate clinical and radiological data., Results: We included 271 cases with diagnoses of adenocarcinoma of the lung (n = 201), squamous cell carcinoma of the lung (n = 53), unspecified NSCLC (n = 8) and other carcinomas (n = 9). TTF-1 and napsin A had sensitivities of 99.0% and 91.9%, respectively, positive predictive values (PPVs) of 90.8% and 90.3%, respectively, and accuracies of 91.0% for adenocarcinoma of the lung. Napsin A had a higher specificity than TTF-1 (90.2% vs 62.8%). Both CK5 and P63 had high sensitivities (95.4% and 97.9%, respectively) and negative predictive values of 96.4% and 96.8%, respectively, for squamous cell carcinoma of the lung. CK5 had a higher specificity than p63 (84.4% and 61.2%, respectively), PPV (80.4% and 70.8%, respectively) and accuracy (88.8% and 79.2%, respectively) for squamous cell carcinoma., Conclusion: All four immunostaining methods had high sensitivities. TTF-1 and napsin A both had high PPV and diagnostic accuracy for adenocarcinoma of the lung, whereas CK5 had an equally high PPV and accuracy for squamous cell carcinoma of the lung. The specificity of napsin A for adenocarcinoma was higher than that of TTF-1. The specificity of CK5 for squamous cell carcinoma was higher than p63., (© 2019 John Wiley & Sons Ltd.)

Tuberculous effusion is a common disease entity with a spectrum of presentations from a largely benign effusion, which resolves completely, to a complicated effusion with loculations, pleural thickening and even frank empyema, all of which may have a lasting effect on lung function. The pathogenesis is a combination of true pleural infection and an effusive hypersensitivity reaction, compartmentalized within the pleural space. Diagnostic thoracentesis with thorough pleural fluid analysis including biomarkers such as adenosine deaminase and gamma interferon achieves high accuracy in the correct clinical context. Definitive diagnosis may require invasive procedures to demonstrate histological evidence of caseating granulomas or microbiological evidence of the organism on smear or culture. Drug resistance is an emerging problem that requires vigilance and extra effort to acquire a complete drug sensitivity profile for each tuberculous effusion treated. Nucleic acid amplification tests such as Xpert MTB/RIF can be invaluable in this instance; however, the yield is low in pleural fluid. Treatment consists of standard anti-tuberculous therapy or a guideline-based individualized regimen in the case of drug resistance. There is low-quality evidence that suggests possible benefit from corticosteroids; however, they are not currently recommended due to concomitant increased risk of adverse effects. Small studies report some short- and long-term benefit from interventions such as therapeutic thoracentesis, intrapleural fibrinolytics and surgery but many questions remain to be answered., (© 2019 Asian Pacific Society of Respirology.)