Computed tomography chest findings in post-acute COVID-19 lung disease at a South African regional hospital - a descriptive study.

Introduction: whilst many studies have focused on acute and chronic complications of COVID-19, few studies have been performed on the immediate post-acute COVID-19 phase complications. The objective of the study was to describe computed tomography (CT) imaging findings in patients from a South African (SA) cohort during the post-acute COVID-19 phase. To describe the findings using existing CT description systems and, if present, pulmonary imaging findings unique to our cohort. Methods: a review of CT chest examinations performed over the second wave of COVID-19 in SA for post-acute COVID-19 cardiorespiratory complaints at Worcester Hospital. The CT findings were described using a modified semi-quantitative tabulation method. Results: eight males and 12 females met the inclusion criteria with a mean age of 56 years. Half had hypertension, 11 had diabetes, two had human immunodeficiency virus (HIV), half had raised D-dimers and six had pre-existing lung disease. The predominant parenchymal pattern was mixed ground glass and reticular changes in a diffuse/peripheral multilobar distribution with relative sparing of the left upper lobe. Four cases demonstrated pulmonary emboli, 50% pulmonary hypertension, three pleural effusions and nine lymphadenopathy. None of the cases had evidence of active pulmonary tuberculosis. Conclusion: CT lung findings appear to mirror global findings with expected evolutionary differences. An interesting observation was the relative sparing of the left upper lobe. Reporting using the modified table proved efficient. Real-world extrapolation of our findings is limited by low-case numbers.

Understanding the biology, morbidity and social contexts of adolescent tuberculosis: a prospective observational cohort study protocol (Teen TB).

INTRODUCTION: A considerable burden of the tuberculosis (TB) epidemic is found in adolescents. The reasons for increased susceptibility to TB infection and higher incidence of TB disease in adolescence, compared with the 5-10 years old age group, are incompletely understood. Despite the pressing clinical and public health need to better understand and address adolescent TB, research in this field remains limited. METHODS AND ANALYSIS: Teen TB is an ongoing prospective observational cohort study that aims to better understand the biology, morbidity and social context of adolescent TB. The study plans to recruit 50 adolescents (10-19 years old) with newly diagnosed microbiologically confirmed pulmonary TB disease and 50 TB-exposed controls without evidence of TB disease in Cape Town, South Africa, which is highly endemic for TB. At baseline, cases and controls will undergo a detailed clinical evaluation, chest imaging, respiratory function assessments and blood collection for viral coinfections, inflammatory cytokines and pubertal hormone testing. At 2 weeks, 2 months and 12 months, TB disease cases will undergo further chest imaging and additional lung function testing to explore the patterns of respiratory abnormalities. At week 2, cases will complete a multicomponent quantitative questionnaire about psychological and social impacts on their experiences and longitudinal, in-depth qualitative data will be collected from a nested subsample of 20 cases and their families. ETHICS AND DISSEMINATION: The study protocol has received ethical approval from the Stellenbosch University Health Research Ethics Committee (N19/10/148). The study findings will be disseminated through peer-reviewed publications, academic conferences and formal presentations to health professionals. Results will also be made available to participants and caregivers.

Biomarkers to predict FDG PET/CT activity after the standard duration of treatment for spinal tuberculosis: An exploratory study.

OBJECTIVES: 18F-Fluorodeoxyglucose (FDG) Positron Emission Tomography- Computed Tomography (PET/CT) scans can be used to assess healing following treatment for spinal tuberculosis (TB) but have limited accessibility and high cost. This study investigated the association between immune biomarkers and FDG-PET/CT activity after ≥9 months of treatment for spinal TB. METHODS: Patients who had completed ≥9 months of treatment for spinal TB were recruited from a major hospital in the Western Cape, South Africa. Participants underwent a FDG-PET/CT scan and FDG- PET/CT activity was quantified for all spinal and extra-spinal sites. Participants also provided a blood sample, which was evaluated for 19 cytokines along with erythrocyte sedimentation rate (ESR). Correlations and multiple regression analyses were used to investigate the association between biomarkers and PET/CT measures. RESULTS: Twenty-eight patients were recruited, of whom 24 (86%) had spinal and/or extra-spinal FDG-PET/CT activity. In the strongest multiple regression model, CXCL10/IP-10, VEGFA, IFN-γ, CRP and Factor D/Adipsin explained 52% of the variation in overall maximal FDG uptake. Conventional monitoring marker ESR showed no significant association with PET/CT measures. CONCLUSIONS: The current findings offered encouragement that biomarkers to predict FDG-PET/CT activity may show some promise and identified candidate biomarkers for further investigation in this regard.

Relative Sparing of the Left Upper Zone on Chest Radiography in Severe COVID-19 Pneumonia.

The radiological findings of COVID-19 are well-described, including its evolution. In an earlier report of admission chest radiographs of patients with COVID-19, we anecdotally noted relative sparing of the left upper zone (LUZ). We subsequently aimed to describe the main chest radiograph findings in another cohort, focusing on zonal predominance. The admission chest radiographs of 111 patients with CO-VID-19 pneumonia requiring intensive care admission were reviewed by 2 thoracic radiologists and categorized according to the predominant pattern into either ground-glass opacities (GGOs), alveolar infiltrates and/or consolidation, or reticular and/or nodular infiltrates or an equal combination of both, and the extent of disease involvement of each of the zones using a modified Radiologic Assessment of Lung Edema (RALE) score. Parenchymal changes were detected in all. In total, 106 radiographs showed GGOs, alveolar infiltrates, and/or consolidation, and 5 had a combination of reticular/nodular infiltrates as well as GGOs, alveolar infiltrates, and/or consolidation. The LUZ had a significant lower grading score than the right upper zone: 1 versus 2 (p < 0.001). Likewise, the upper zones had a significant lower score than the mid and lower zones (p < 0.001). Our findings confirmed the relative sparing of the LUZ in severe COVID-19 pneumonia.

PROVE-Pre-Eclampsia Obstetric Adverse Events: Establishment of a Biobank and Database for Pre-Eclampsia.

Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. The burden of disease lies mainly in low-middle income countries. The aim of this project is to establish a pre-eclampsia biobank in South Africa to facilitate research in the field of pre-eclampsia with a focus on phenotyping severe disease.The approach of our biobank is to collect biological specimens, detailed clinical data, tests, and biophysical examinations, including magnetic resonance imaging (MRI) of the brain, MRI of the heart, transcranial Doppler, echocardiography, and cognitive function tests.Women diagnosed with pre-eclampsia and normotensive controls are enrolled in the biobank at admission to Tygerberg University Hospital (Cape Town, South Africa). Biological samples and clinical data are collected at inclusion/delivery and during the hospital stay. Special investigations as per above are performed in a subset of women. After two months, women are followed up by telephonic interviews. This project aims to establish a biobank and database for severe organ complications of pre-eclampsia in a low-middle income country where the incidence of pre-eclampsia with organ complications is high. The study integrates different methods to investigate pre-eclampsia, focusing on improved understanding of pathophysiology, prediction of organ complications, and potentially future drug evaluation and discovery.

A 48-Year-Old South African Woman with Rheumatoid Arthritis and Lung Nodules.

CASE PRESENTATION: We present the case of a 48-year-old South African woman with no smoking history, and seropositive rheumatoid arthritis diagnosed in 2001. She was treated with chloroquine (150 mg, 4 times per week) and methotrexate (30 mg weekly) with well-controlled symptoms until 2015, when she developed a disease flare. Her treatment regimen was changed to leflunomide (20 mg daily) monotherapy with subsequent symptom control. Biologic agents were not accessible because of cost constraints.

High-resolution computed tomography features of lung disease in perinatally HIV-infected adolescents on combined antiretroviral therapy.

INTRODUCTION: Chronic lung disease is common in perinatally HIV-infected children as they increasingly surviving into adolescence. There are few data on the radiologic spectrum of disease in this population. METHODS: Contrasted high-resolution computed tomography (HRCT) was performed in ambulatory South African adolescents enrolled in a prospective study of perinatally-infected adolescents aged 9 to 14 years established on combined antiretroviral therapy (cART) and followed for 36 months. Consecutive participants with reduced lung function (defined by a forced expiratory volume in 1 second [FEV1] of <80% normal and/or lung diffusion capacity [DLCO] <80% normal] underwent HRCT. History, clinical, and laboratory data were collected. Two radiologists blinded to clinical data and to each other, reported scans using standardized methodology; a third radiologist resolved discrepancies. RESULTS: Amongst 100 participants undergoing HRCT, median age was 13.8 years (12.8-15.1). The median duration on cART was 8.4 years (IQR = 5.7-9.8). Mosaic attenuation was the most common finding (73%). Of these 71 (91%) demonstrated associated air trapping radiologically consistent with bronchiolitis obliterans. Bronchiectasis occurred in 39% with significant correlation between extent of bronchiectasis and mosaic attenuation (r = 0.57, P < .001). Prior hospitaliszation for childhood pneumonia at any time before enrollment was associated with mosaic attenuation (OR = 3.9, 95%CI, [1.2-12.5]); prior pulmonary tuberculosis (TB) was associated with the combination of mosaic attenuation and bronchiectasis (OR = 4.9, 95%CI, [1.6-15.7]). Most participants (86%) with mosaic attenuation had stage III or IV HIV disease at time of HIV diagnosis (OR = 3.6; [0.9-14.9]). Inter observer agreement between the two readers was good for bronchiectasis (K = 0.71) and moderate for mosaic attenuation (K = 0.51). DISCUSSION: Despite well-controlled HIV and long duration of cART, HRCT changes were common in perinatally HIV-infected adolescents. There was a high prevalence of small airways disease with and without associated bronchiectasis. These changes were associated with prior pulmonary TB or prior severe pneumonia. Strategies to prevent and treat early life respiratory infection must be strengthened to reduce the burden of chronic lung disease in HIV-infected adolescents.

A semi-automatic technique to quantify complex tuberculous lung lesions on 18F-fluorodeoxyglucose positron emission tomography/computerised tomography images.

BACKGROUND: There is a growing interest in the use of 18F-FDG PET-CT to monitor tuberculosis (TB) treatment response. However, TB causes complex and widespread pathology, which is challenging to segment and quantify in a reproducible manner. To address this, we developed a technique to standardise uptake (Z-score), segment and quantify tuberculous lung lesions on PET and CT concurrently, in order to track changes over time. We used open source tools and created a MATLAB script. The technique was optimised on a training set of five pulmonary tuberculosis (PTB) cases after standard TB therapy and 15 control patients with lesion-free lungs. RESULTS: We compared the proposed method to a fixed threshold (SUV > 1) and manual segmentation by two readers and piloted the technique successfully on scans of five control patients and five PTB cases (four cured and one failed treatment case), at diagnosis and after 1 and 6 months of treatment. There was a better correlation between the Z-score-based segmentation and manual segmentation than SUV > 1 and manual segmentation in terms of overall spatial overlap (measured in Dice similarity coefficient) and specificity (1 minus false positive volume fraction). However, SUV > 1 segmentation appeared more sensitive. Both the Z-score and SUV > 1 showed very low variability when measuring change over time. In addition, total glycolytic activity, calculated using segmentation by Z-score and lesion-to-background ratio, correlated well with traditional total glycolytic activity calculations. The technique quantified various PET and CT parameters, including the total glycolytic activity index, metabolic lesion volume, lesion volumes at different CT densities and combined PET and CT parameters. The quantified metrics showed a marked decrease in the cured cases, with changes already apparent at month one, but remained largely unchanged in the failed treatment case. CONCLUSIONS: Our technique is promising to segment and quantify the lung scans of pulmonary tuberculosis patients in a semi-automatic manner, appropriate for measuring treatment response. Further validation is required in larger cohorts.

Inter-rater reliability in the radiological classification of renal injuries.

INTRODUCTION: Although many radiologists invoke the surgical classification of renal injury proposed by the American Association for Surgery in Trauma (AAST), there has been only limited work on the role of the AAST system as an imaging stratification. The aim was to determine the inter-rater reliability (IRR) amongst radiologists and urologists using the AAST system. METHODS: A 1-year retrospective study of consecutive patients with computed tomography (CT) evidence of renal trauma managed at a Level 1 trauma center. Three radiologists and three urologists independently stratified the presentation CT findings according to the AAST renal trauma classification. Agreement between independent raters and mutually exclusive groups was determined utilizing weighted kappa coefficients. RESULTS: One hundred and one patients were included. Individual inter-observer agreements ranged from 54/101 (53.4%) to 62/101 (61.4%), with corresponding weighted kappa values from 0.61 to 0.69, constituting substantial agreement. Urologists achieved intra-disciplinary agreement in 49 cases (48.5%) and radiologists in 36 cases (35.6%). Six-reader agreement was achieved in 24 cases (23.7%). The AAST grade I injuries had the highest level of agreement, overall. CONCLUSION: The finding of substantial IRR amongst radiologists and urologists utilizing the AAST system supports continued use of the broad parameters of the AAST system, with some modification in specific categories with lower agreement.

Recurrent Pulmonary Aneurysms: Hughes-Stovin Syndrome on the Spectrum of Behçet Disease.

In this report, we describe a male patient who presented with recurrent life-threatening hemoptysis due to the sequential formation of multiple pulmonary aneurysms. Both pulmonary artery coil embolization and right lower lobectomy were performed, with limited success. The patient experienced extensive bilateral femoral DVT extending into the inferior vena cava, with massive hemoptysis, fulfilling the diagnosis of Hughes-Stovin syndrome. A final diagnosis of Behçet disease was made following extensive investigation, and the patient responded well to prednisone 20 mg orally and azathioprine 100 mg orally.

Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure.

The absence of a gold standard to determine when antibiotics induce a sterilizing cure has confounded the development of new approaches to treat pulmonary tuberculosis (PTB). We detected positron emission tomography and computerized tomography (PET-CT) imaging response patterns consistent with active disease, along with the presence of Mycobacterium tuberculosis (MTB) mRNA in sputum and bronchoalveolar lavage samples, in a substantial proportion of adult, HIV-negative patients with PTB after a standard 6-month treatment plus 1 year follow-up, including patients with a durable cure and others who later developed recurrent disease. The presence of MTB mRNA in the context of nonresolving and intensifying lesions on PET-CT images might indicate ongoing transcription, suggesting that even apparently curative treatment for PTB may not eradicate all of the MTB bacteria in most patients. This suggests an important complementary role for the immune response in maintaining a disease-free state. Sterilizing drugs or host-directed therapies, and better treatment response markers, are probably needed for the successful development of improved and shortened PTB-treatment strategies.

Reliability and diagnostic performance of CT imaging criteria in the diagnosis of tuberculous meningitis.

INTRODUCTION: Abnormalities on CT imaging may contribute to the diagnosis of tuberculous meningitis (TBM). Recently, an expert consensus case definition (CCD) and set of imaging criteria for diagnosing basal meningeal enhancement (BME) have been proposed. This study aimed to evaluate the sensitivity, specificity and reliability of these in a prospective cohort of adult meningitis patients. METHODS: Initial diagnoses were based on the CCD, classifying patients into: 'Definite TBM' (microbiological confirmation), 'Probable TBM' (diagnostic score ≥10), 'Possible TBM' (diagnostic score 6-9), 'Not TBM' (confirmation of an alternative diagnosis) or 'Uncertain' (diagnostic score of <6). CT images were evaluated independently on two occasions by four experienced reviewers. Intra-rater and inter-rater agreement were calculated using the kappa statistic. Sensitivities and specificities were calculated using both 'Definite TBM' and either 'Definite TBM' or 'Probable TBM' as gold standards. RESULTS: CT scan criteria for BME had good intra-rater agreement (κ range 0.35-0.78) and fair to moderate inter-rater agreement (κ range 0.20-0.52). Intra- and inter-rater agreement on the CCD components were good to fair (κ  =  ranges 0.47-0.81 and 0.21-0.63). Using 'Definite TBM' as a gold standard, the criteria for BME were very specific (61.5%-100%), but insensitive (5.9%-29.4%). Similarly, the imaging components of the CCD were highly specific (69.2-100%) but lacked sensitivity (0-56.7%). Similar values were found when using 'Definite TBM' or 'Probable TBM' as a gold standard. DISCUSSION: The fair to moderate inter-rater agreement and poor sensitivities of the criteria for BME suggest that little reliance should be placed in these features in isolation. While the presence of the CCD criteria of acute infarction or tuberculoma(s) appears useful as rule-in criteria, their absence is of little help in excluding TBM. The CCD and criteria for BME, as well as any new criteria, need to be standardized and validated in prospective cohort studies.

Cavitating pulmonary tuberculosis in children: correlating radiology with pathogenesis.

BACKGROUND: Cavitating pulmonary tuberculosis (PTB) is generally known as a disease of adults, with children typically having features of primary PTB. OBJECTIVE: To group children with PTB and cavities according to possible pathogenesis by evaluating the clinical and radiological findings. MATERIALS AND METHODS: The clinical and radiological findings in ten randomly selected children with PTB and cavitations on chest radiographs were retrospectively reviewed and evaluated. RESULTS: Three groups emerged: group 1 (four children) had cavities, usually single and unilateral in the classic upper lobe distribution of postprimary PTB; group 2 (three children) developed progressive primary spread of disease with extensive and bilateral pulmonary cavities; and group 3 (three children) developed cavities secondary to airway obstruction by mediastinal lymph nodes with consequent distal collapse and consolidation. Children in group 1 responded well to treatment and had unremarkable recoveries. Children in group 2 were all below 2 years of age with complicated recoveries. Children in group 3 had frequent complications resulting in one fatality. CONCLUSION: Cavities in PTB in children may arise by one of three possible mechanisms with a relatively equal incidence. A study is underway to determine the incidence of cavity formation associated with mediastinal lymphadenopathy and airway obstruction.