Publications

We sought to compare the diagnostic performance of coronary computed tomography angiography (CCTA), computed tomography perfusion (CTP), and computed tomography (CT)-fractional flow reserve (FFR) for assessing the functional significance of coronary stenosis as defined by invasive FFR in patients with known or suspected coronary artery disease (CAD). CCTA has proved clinically useful for excluding obstructive CAD because of its high sensitivity and negative predictive value (NPV); however, the ability of CTA to identify functionally significant CAD has remained challenging. We searched PubMed/Medline for studies evaluating CCTA, CTP, or CT-FFR for the noninvasive detection of obstructive CAD compared with catheter-derived FFR as the reference standard. Pooled sensitivity, specificity, PPV, NPV, likelihood ratios, and odds ratio of all diagnostic tests were assessed. Eighteen studies involving a total of 1,535 patients were included. CTA demonstrated a pooled sensitivity of 0.92, specificity 0.43, PPV of 0.56, and NPV of 0.87 on a per-patient level. CT-FFR and CTP increased the specificity to 0.72 and 0.77, respectively (p = 0.004 and p = 0.0009) resulting in higher point estimates for PPV 0.70 and 0.83, respectively. There was no improvement in the sensitivity. The CTP protocol involved more radiation (3.5 mSv CCTA vs 9.6 mSv CTP) and a higher volume of iodinated contrast (145 ml). In conclusion, CTP and CT-FFR improve the specificity of CCTA for detecting functionally significant stenosis as defined by invasive FFR on a per-patient level; both techniques could advance the ability to noninvasively detect the functional significance of coronary lesions.

BACKGROUND

Autopsy studies of HIV/AIDS-related hospital deaths in sub-Saharan Africa reveal frequent failure of pre-mortem diagnosis of tuberculosis (TB), which is found in 34-64 % of adult cadavers. We determined the overall prevalence and predictors of TB among consecutive unselected HIV-positive adults requiring acute hospital admission and the comparative diagnostic yield obtained by screening urine and sputum samples obtained on day 1 of admission with Xpert MTB/RIF (Xpert).

METHODS

To determine overall TB prevalence accurately, comprehensive clinical sampling (sputum, urine, blood plus other relevant samples) was done and TB was defined by detection of Mycobacterium tuberculosis in any sample using Xpert and/or mycobacterial liquid culture. To evaluate a rapid screening strategy, we compared the diagnostic yield of Xpert testing sputum samples and urine samples obtained with assistance from a respiratory study nurse in the first 24 h of admission.

RESULTS

Unselected HIV-positive acute adult new medical admissions (n = 427) who were not receiving TB treatment were enrolled irrespective of clinical presentation or symptom profile. From 2,391 cultures and Xpert tests done (mean, 5.6 tests/patient) on 1,745 samples (mean, 4.1 samples/patient), TB was diagnosed in 139 patients (median CD4 cell count, 80 cells/μL). TB prevalence was very high (32.6 %; 95 % CI, 28.1-37.2 %; 139/427). However, patient symptoms and risk factors were poorly predictive for TB. Overall, ≥1 non-respiratory sample(s) tested positive in 115/139 (83 %) of all TB cases, including positive blood cultures in 41/139 (29.5 %) of TB cases. In the first 24 h of admission, sputum (spot and/or induced samples) and urine were obtainable from 37.0 % and 99.5 % of patients, respectively (P <0.001). From these, the proportions of total TB cases (n = 139) that were diagnosed by Xpert testing sputum, urine or both sputum and urine combined within the first 24 h were 39/139 (28.1 %), 89/139 (64.0 %) and 108/139 (77.7 %) cases, respectively (P <0.001).

CONCLUSIONS

The very high prevalence of active TB and its non-specific presentation strongly suggest the need for routine microbiological screening for TB in all HIV-positive medical admissions in high-burden settings. The incremental diagnostic yield from Xpert testing urine was very high and this strategy might be used to rapidly screen new admissions, especially if sputum is difficult to obtain.

Thymic epithelial cells (TECs) support T cell development in the thymus. Cortical thymic epithelial cells (cTECs) facilitate positive selection of developing thymocytes whereas medullary thymic epithelial cells (mTECs) facilitate the deletion of self-reactive thymocytes in order to prevent autoimmunity. The mTEC compartment is highly dynamic with continuous maturation and turnover, but the genetic regulation of these processes remains poorly understood. MicroRNAs (miRNAs) are important regulators of TEC genetic programs since miRNA-deficient TECs are severely defective. However, the individual miRNAs important for TEC maintenance and function and their mechanisms of action remain unknown. Here, we demonstrate that miR-205 is highly and preferentially expressed in mTECs during both thymic ontogeny and in the postnatal thymus. This distinct expression is suggestive of functional importance for TEC biology. Genetic ablation of miR-205 in TECs, however, neither revealed a role for miR-205 in TEC function during homeostatic conditions nor during recovery from thymic stress conditions. Thus, despite its distinct expression, miR-205 on its own is largely dispensable for mTEC biology.