Background: Malignant Pleural Mesothelioma (MPM) is an aggressive disease related to asbestos exposure, with no effective therapeutic options. Methods: We undertook unsupervised analyses of RNA-sequencing data of 284 MPMs, with no assumption of discreteness. Using immunohistochemistry, we performed an orthogonal validation on a subset of 103 samples and a biological replication in an independent series of 77 samples. Findings: A continuum of molecular profiles explained the prognosis of the disease better than any discrete model. The immune and vascular pathways were the major sources of molecular variation, with strong differences in the expression of immune checkpoints and pro-angiogenic genes; the extrema of this continuum had specific molecular profiles: a "hot" bad-prognosis profile, with high lymphocyte infiltration and high expression of immune checkpoints and pro-angiogenic genes; a "cold" badprognosis profile, with low lymphocyte infiltration and high expression of pro-angiogenic genes; and a "VEGFR2+/VISTA+" better-prognosis profile, with high expression of immune checkpoint VISTA and proangiogenic gene VEGFR2. We validated the gene expression levels at the protein level for a subset of five selected genes belonging to the immune and vascular pathways (CD8A, PDL1, VEGFR3, VEGFR2, and VISTA), in the validation series, and replicated the molecular profiles as well as their prognostic value in the replication series. Interpretation: The prognosis of MPM is best explained by a continuous model, which extremes show specific expression patterns of genes involved in angiogenesis and immune response.

This study is registered on ClinicalTrials.gov, number NCT01613365.

Variation of atmospheric pressure, relative humidity, rainfall, wind speed and temperature were not significantly related to the onset of the first episode of PSP in healthy patients. These results suggest that the scientific community should focus on other possible aetiological factors than airway pressure modifications.

A 62-year-old woman underwent a reduction of a proximal reduced humeral fracture, which was fixed by 3 Kirschner pins. One year later, the orthopedic surgeon failed to remove one of the wires. The patient was lost to follow-up, and 4 years later, she presented with hemoptysis, revealing migration of the pin to the lung. The pin was removed through a thoracotomy. Migration to the lung is often revealed by hemoptysis or pneumothorax. Close follow-up and early removal of the pins are mandatory.