OBJECTIVE: We compared the haemodynamic effects of riociguat in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent/recurrent CTEPH after pulmonary endarterectomy in the Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Trial 1 study.
METHODS: Patients with inoperable or persistent/recurrent CTEPH (n=261; mean± SD age 59±14 years; 66% women) were randomised to riociguat (up to 2.5 mg three times daily) or placebo. Haemodynamic parameters were assessed at baseline and week 16.

RESULTS: Riociguat decreased pulmonary vascular resistance (PVR) in inoperable (n=189; least-squares mean difference: -285 dyn s/cm(5) (95% CI -357 to -213); p<0.0001) and persistent/recurrent (n=72; -131 dyn s/cm(5) (95% CI -214 to -48); p=0.0025) patients. Cardiac index improved in inoperable patients by a least-squares mean difference of +0.6 L/min/m(2) (95% CI 0.4 to 0.7; p<0.0001), while in persistent/recurrent patients the change was +0.2 L/min/m(2) (95% CI -0.1 to 0.5; p=0.17). Mean pulmonary artery pressure decreased in inoperable and persistent/recurrent patients(-4.7 mm Hg (95% CI -6.9 to -2.6; p<0.0001 and -4.8 mm Hg (-8.2 to -1.5; p=0.0055), respectively). For all patients, changes in 6 min walk distance correlated with changes in PVR (r=-0.29 (95% CI -0.41 to -0.17); p<0.0001) and cardiac index (r=0.23 (95% CI 0.10 to 0.35); p=0.0004).

CONCLUSIONS: Riociguat improved haemodynamics in patients with inoperable CTEPH or persistent/recurrent CTEPH.
TRIAL REGISTRATION NUMBER: NCT00855465.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and ultimately fatal disorder for which there is no cure. While the disease is by definition idiopathic, accumulating evidence, including familial aggregation of cases and the occurrence of pulmonary fibrosis in the context of a number of rare genetic disorders, indicates that genetic factors contribute significantly to the pathogenesis of IPF. Several disease-associated genetic variants, both rare and common, have been identified in familial and sporadic IPF. While the full clinical implications of these genetic associations remain to be elucidated, observational studies suggest that genotype influences the development of the disease and its outcome.

Available data indicate that genetics has the potential to identify individuals at risk of IPF, classify patients more precisely, clarify the key pathways involved in disease pathogenesis and eventually develop more effective targeted therapies. Considerable research is required before a comprehensive disease fingerprint of IPF can be delivered. Nevertheless, the application of rapidly evolving molecular biology and genomic technologies combined with appropriate bioinformatic methodology offers an unprecedented and realistic opportunity to achieve this goal.

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BACKGROUND: Staging of mediastinal lymph nodes in non-small cell lung cancer (NSCLC) is mandatory. The maximum Standard Uptake Value (SUVmax) obtained using F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is the best non-invasive technique available for this evaluation, but its performance varies from center to center. The aim of the present study was to identify FDG-PET predictors of mediastinal malignancy that are able to minimize intercenter variability and improve the selection of subsequent staging procedures.

METHOD: A multicenter study of NSCLC patients staged through FDG-PET and endobronchial ultrasonography with needle aspiration (EBUS-NA) was performed using therapeutic surgery with systematic nodal dissection as gold standard. Intercenter variability and predictive power for mediastinal malignancy of different FDG-PET measures were assessed, as well as the role of these measures for selecting additional staging procedures.

RESULTS: One hundred and twenty-one NSCLC patients, of whom 94 (72%) had ≥1 hypermetabolic spots in the mediastinum, were included in the study. Mean SUVmax of the primary tumor was 12.3 (SD 6.3), and median SUVmax of the highest hypermetabolic spots in the mediastinum was 3.9 (IQR 2.4-7). Variability of FDG-PET measures between hospitals was statistically significant (p = 0.016 and p < 0.001 respectively), but lost significance when SUVmax in the mediastinum was expressed as a ratio or a subtraction from the primary tumor (SUVmax mediastinum/tumor, p = 0.083; and SUVmax mediastinum - tumor, p = 0.428 respectively). SUVmax mediastinum/tumor showed higher accuracy in the ROC analysis (AUC 0.77 CI 0.68-0.85, p < 0.001), and showed predictive power for mediastinal malignancy when using a 0.4 cutoff (OR 6.62, 95%CI 2.98-14.69). Sensitivities and negative predictive values of clinical staging through EBUS-NA attained values ranging between 57% and 92% after FDG-PET, which improved with additional techniques when the tumor had a diameter >3 cm and/or a SUVmax mediastinum/tumor ratio >0.4.

CONCLUSION: The SUVmax mediastinum/tumor ratio is a good predictor of regional tumor extension in NSCLC. This measure is not influenced by intercenter variability and has an accuracy of over 70% for the identification of malignancy when using a 0.4 cutoff.

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SETTING: The utility of interferon-gamma release assays (IGRAs), such as the QuantiFERON-TB Gold In-Tube (QFT-GIT) test, in diagnosing active tuberculosis (TB) in children is unclear and depends on the epidemiological setting.
OBJECTIVE: To evaluate the performance of QFT-GIT for TB diagnosis in children living in Morocco, an intermediate TB incidence country with high bacille Calmette-Gurin vaccination coverage.
DESIGN: We prospectively recruited 109 Moroccan children hospitalised for clinically suspected TB, all of whom were tested using QFT-GIT.

RESULTS: For 81 of the 109 children, the final diagnosis was TB. The remaining 28 children did not have TB. QFT-GIT had a sensitivity of 66% (95%CI 5277) for the diagnosis of TB, and a specificity of 100% (95%CI 88100). The tuberculin skin test (TST) had lower sensitivity, at 46% (95%CI 3360), and its concordance with QFT-GIT was limited (69%). Combining QFT-GIT and TST results increased sensitivity to 83% (95%CI 6992).

CONCLUSION: In epidemiological settings such as those found in Morocco, QFT-GIT is more sensitive than the TST for active TB diagnosis in children. Combining the TST and QFT-GIT would be useful for the diagnosis of active TB in children, in combination with clinical, radiological and laboratory data.