Blood RNA signatures outperform CRP triage of tuberculosis lymphadenitis and pericarditis.

Background: Limited data are available on the diagnostic accuracy of blood RNA biomarker signatures for extrapulmonary TB (EPTB). We addressed this question among people investigated for TB lymphadenitis and TB pericarditis, in Cape Town, South Africa. Methods: We enrolled 440 consecutive adults referred to a hospital for invasive sampling for presumptive TB lymphadenitis (n=300) or presumptive TB pericarditis (n=140). Samples from the site of disease underwent culture and/or molecular testing for Mycobacterium tuberculosis complex (Mtb). Discrimination of patients with and without TB defined by microbiology or cytology reference standards was evaluated using seven previously reported blood RNA signatures by area under the receiver-operating characteristic curve (AUROC) and sensitivity/specificity at predefined thresholds, benchmarked against blood C-reactive protein (CRP) and the World Health Organization (WHO) target product profile (TPP) for a TB triage test. Decision curve analysis (DCA) was used to evaluate the clinical utility of the best performing blood RNA signature and CRP. Results: Data from 374 patients for whom results were available from at least one microbiological test from the site of disease, and blood CRP and RNA measurements, were included. Using microbiological results as the reference standard in the primary analysis (N=204 with TB), performance was similar across lymphadenitis and pericarditis patients. In the pooled analysis of both cohorts, all RNA signatures had comparable discrimination with AUROC point estimates ranging 0.77-0.82, superior to that of CRP (0.61, 95% confidence interval 0.56-0.67). The best performing signature (Roe3) achieved an AUROC of 0.82 (0.77-0.86). At a predefined threshold of 2 standard deviations (Z2) above the mean of a healthy reference control group, this signature achieved 78% (72-83%) sensitivity and 69% (62-75%) specificity. In this setting, DCA revealed that Roe3 offered greater net benefit than other approaches for services aiming to reduce the number needed to investigate with confirmatory testing to <4 to identify each case of TB. Interpretation: RNA biomarkers show better accuracy and clinical utility than CRP to trigger confirmatory TB testing in patients with TB lymphadenitis and TB pericarditis, but still fall short of the WHO TPP for TB triage tests. Funding: South African MRC, EDCTP2, NIH/NIAID, Wellcome Trust, NIHR, Royal College of Physicians London.

Bad company? The pericardium microbiome in people investigated for tuberculosis pericarditis in an HIV-prevalent setting.

Background: The microbiome likely plays a role in tuberculosis (TB) pathogenesis. We evaluated the site-of-disease microbiome and predicted metagenome in people with presumptive tuberculous pericarditis, a major cause of mortality, and explored for the first time, the interaction between its association with C-reactive protein (CRP), a potential diagnostic biomarker and the site-of-disease microbiome in extrapulmonary TB. Methods: People with effusions requiring diagnostic pericardiocentesis (n=139) provided background sampling controls and pericardial fluid (PF) for 16S rRNA gene sequencing analysed using QIIME2 and PICRUSt2. Blood was collected to measure CRP. Results: PF from people with definite (dTB, n=91), probable (pTB, n=25), and non- (nTB, n=23) tuberculous pericarditis differed in ß-diversity. dTBs were, vs. nTBs, Mycobacterium-, Lacticigenium-, and Kocuria- enriched. Within dTBs, HIV-positives were Mycobacterium-, Bifidobacterium- , Methylobacterium- , and Leptothrix -enriched vs. HIV-negatives and HIV-positive dTBs on ART were Mycobacterium - and Bifidobacterium -depleted vs. those not on ART. Compared to nTBs, dTBs exhibited short-chain fatty acid (SCFA) and mycobacterial metabolism microbial pathway enrichment. People with additional non-pericardial involvement had differentially PF taxa (e.g., Mycobacterium -enrichment and Streptococcus -depletion associated with pulmonary infiltrates). Mycobacterium reads were in 34% (31/91), 8% (2/25) and 17% (4/23) of dTBs, pTBs, and nTBs, respectively. ß-diversity differed between patients with CRP above vs. below the median value ( Pseudomonas -depleted). There was no correlation between enriched taxa in dTBs and CRP. Conclusions: PF is compositionally distinct based on TB status, HIV (and ART) status and dTBs are enriched in SCFA-associated taxa. The clinical significance of these findings, including mycobacterial reads in nTBs and pTBs, requires evaluation.

Subacute dual stent thromboses in a COVID-19-positive patient.

The hypercoagulable state of COVID-19 is resulting in an increasing number of unexpected venous and arterial thromboses in patients. We report a case of subacute dual coronary stent thrombosis in the setting of COVID-19 and we provide a brief review of current management recommendations.

Dynamic Left Ventricular Outflow Tract Obstruction Post-Transcatheter Aortic Valve Replacement.

We describe the first case of successful management of left ventricular outflow tract obstruction developing late after transcatheter aortic valve replacement with right ventricular apical pacing. The possible mechanisms of obstruction resolution are described. (Level of Difficulty: Advanced.).

Extensive pulmonary metastases in young boy with primary cardiac angiosarcoma: a case report.

BACKGROUND: Malignant primary cardiac neoplasms are rare and primary cardiac angiosarcoma is the most common and aggressive subtype. It most commonly presents in middle-aged males and due to its non-specific clinical presentation, the diagnosis is often delayed until advanced disease is already present. Clinical presentation is determined by manifestations of local infiltration or metastatic disease and making an early diagnosis is extremely challenging. CASE SUMMARY: A 15-year-old previously healthy boy was admitted to the emergency department with a history of pathological weight loss and functional decline. The patient was found to have a left-sided pneumothorax as well as bilateral diffusely spread pulmonary nodules on plain chest radiograph. Computed tomography chest confirmed widespread pulmonary metastases and a right atrial filling defect. Echocardiography revealed a right atrial tumour and transvenous endomyocardial biopsy of the tumour was done under fluoroscopic and echocardiographic guidance. A diagnosis of primary cardiac angiosarcoma was made. The patient demised shortly after presentation. DISCUSSION: Primary cardiac angiosarcoma is rare and even more so in patients as young as the case described. The diagnostic process poses several challenges to the clinician, of which the obtaining of a histological sample is one. This case report demonstrates aspects both unique and typical of this rare disease. It also describes an effective option for obtaining tissue for a histological diagnosis in patients whose clinical condition may not allow biopsy under general anaesthesia.

Inferior ST-elevation myocardial infarction managed with a pharmacoinvasive strategy and conservative management of delayed atrioventricular block: classical case report.

BACKGROUND: The 2017 ESC guideline on patients with ST-segment elevation myocardial infarction (STEMI) provides guidance regarding the optimal management of these patients. Transient atrioventricular (AV) block is a relatively common complication of inferior STEMI and its management is also addressed in the guidelines. CASE SUMMARY: A 64-year-old gentleman with multiple cardiovascular risk factors presented to the emergency department with a history of ischaemic type chest pain and evidence of inferior ST-segment elevation on his electrocardiogram (ECG). First-degree AV block was noted on his initial ECG. He was given thrombolytic therapy as part of a pharmacoinvasive strategy of reperfusion. He, however, failed fibrinolytic therapy, and emergency angiography revealed critical disease of the right coronary artery which was successfully stented. Subsequent to reperfusion, he developed complete AV block without evidence of re-infarction, which was managed conservatively with successful resolution of the block after 7 days of expectant management with temporary transvenous pacing. DISCUSSION: We highlight some of the important management principles from the ESC guideline of STEMI including timing and the management of AV block in these patients. In addition, we highlight the role of a pharmacoinvasive strategy for reperfusion where timeous primary percutaneous coronary intervention cannot be performed. The usefulness of such a strategy within the COVID-19 era is also emphasized.

The de Winter's pattern revisited: a case series.

BACKGROUND: The de Winter's electrocardiogram (ECG) pattern signifying proximal left anterior descending (LAD) artery occlusion was first described in 2008. The ECG changes were thought to be static and mechanisms for this were suggested. In addition, the optimal management of these patients was reported to be via a primary percutaneous coronary intervention (PCI) strategy. CASE SUMMARY: Case 1: A 48-year-old gentleman presented with a 2-h history of ischaemic chest pain with initial de Winter's pattern on ECG. This progressed to anterior ST-elevation myocardial infarction (STEMI) complicated by ventricular fibrillation. Emergency angiography revealed a mid-vessel LAD occlusion which was successfully reperfused. Case 2: A 34-year-old female presented with a 2-h history of ischaemic chest pain with initial ECG showing a de Winter's pattern. Due to concerns of performing PCI timeously, a pharmacoinvasive strategy of reperfusion was adopted with resolution of the de Winter's pattern. Urgent angiography revealed a proximal LAD lesion which was successfully stented. DISCUSSION: The two cases highlight that the de Winter's pattern may in fact not be static, but rather lie along the continuum of ischaemia and may evolve into STEMI. In addition, we provide further evidence that if primary PCI cannot be offered in a timeous manner, thrombolytic therapy may be considered in such patients. The de Winter's pattern remains a high-risk ECG pattern that requires early recognition and intervention.

Does access to private healthcare influence potential lung cancer cure rates?

BACKGROUND: Numerous studies show a link between poor socioeconomic status (SES) and late-stage cancer diagnosis. However, this has not been consistently shown looking at non-small-cell lung cancer (NSCLC) in isolation. Despite the extremely high prevalence of lung cancer and disparities in access to healthcare based on health insurance in South Africa, there is a paucity of data on the influence of health insurance (as a surrogate for SES) on stage at presentation of NSCLC. OBJECTIVE: To assess the relationship between health insurance status (and invariably SES) and staging (and therefore resectability) of patients with primary NCSLC at the time of initial presentation. METHODS: Health-insured patients with NSCLC (n=51) were retrospectively compared with NSCLC patients with no health insurance (n=532) with regard to demographics, tumour node metastasis (TNM) staging, and cell type at initial presentation. RESULTS: Patients with no health insurance were younger (mean (standard deviation (SD)) 59.9 (10.1) years) than those with private health insurance (64.2 (9.6) years) (p=0.03). Poorly differentiated NSCLC was significantly more common in the privately health-insured group (23.6%) than among those with no health insurance (4.6%) (p<0.01). Six of 51 NSCLC patients (11.8%) with private health insurance presented with early-stage, potentially curable disease (up to stage IIIA), compared with 55 patients (10.3%) in the uninsured group (p=0.75). CONCLUSIONS: Access to private health insurance did not have a significant impact on stage at initial presentation. The only significant differences were the relatively advanced age at presentation and relatively higher percentage of poorly differentiated NSCLC seen in patients with health insurance.