Chest CT Characteristics are Strongly Predictive of Mortality in Patients with COVID-19 Pneumonia: A Multicentric Cohort Study.

RATIONALE AND OBJECTIVES: The novel coronavirus (COVID-19) has presented a significant and urgent threat to global health and there has been a need to identify prognostic factors in COVID-19 patients. The aim of this study was to determine whether chest computed tomography (CT) characteristics had any prognostic value in patients with COVID-19. MATERIALS AND METHODS: A retrospective analysis of COVID-19 patients who underwent a chest CT-scan was performed in four medical centers. The prognostic value of chest CT results was assessed using a multivariable survival analysis with the Cox model. The characteristics included in the model were the degree of lung involvement, ground glass opacities, nodular consolidations, linear consolidations, a peripheral topography, a predominantly inferior lung involvement, pleural effusion, and crazy paving. The model was also adjusted on age, sex, and the center in which the patient was hospitalized. The primary endpoint was 30-day in-hospital mortality. A second model used a composite endpoint of admission to an intensive care unit or 30-day in-hospital mortality. RESULTS: A total of 515 patients with available follow-up information were included. Advanced age, a degree of pulmonary involvement ≥50% (Hazard Ratio 2.25 [95% CI: 1.378-3.671], p = 0.001), nodular consolidations and pleural effusions were associated with lower 30-day in-hospital survival rates. An exploratory subgroup analysis showed a 60.6% mortality rate in patients over 75 with ≥50% lung involvement on a CT-scan. CONCLUSION: Chest CT findings such as the percentage of pulmonary involvement ≥50%, pleural effusion and nodular consolidation were strongly associated with 30-day mortality in COVID-19 patients. CT examinations are essential for the assessment of severe COVID-19 patients and their results must be considered when making care management decisions.

Laboratory evaluation of the (VIS, IR) scattering matrix of complex-shaped ragweed pollen particles.

Ragweed or Ambrosia artemisiifolia pollen is an important atmospheric constituent affecting the Earth's climate and public health. The literature on light scattering by pollens embedded in ambient air is however rather sparse: polarization measurements are limited to the sole depolarization ratio and pollens are beyond the reach of numerically exact light scattering models mainly due to their tens of micrometre size. Also, ragweed pollen presents a very complex shape, with a small-scale external structure exhibiting spikes that bears some resemblance with coronavirus, but also apertures and micrometre holes. In this paper, to face such a complexity, a controlled-laboratory experiment is proposed to evaluate the scattering matrix of ragweed pollen embedded in ambient air. It is based on a newly-built polarimeter, operating in the infra-red spectral range, to account for the large size of ragweed pollen. Moreover, the ragweed scattering matrix is also evaluated in the visible spectral range to reveal the spectral dependence of the ragweed scattering matrix within experimental error bars. As an output, precise spectral and polarimetric fingerprints for large size and complex-shaped ragweed pollen particles are then provided. We believe our laboratory experiment may interest the light scattering community by complementing other light scattering experiments and proposing outlooks for numerical work on large and complex-shaped particles.

Peritoneal cell-derived mast cells: an in vitro model of mature serosal-type mouse mast cells.

Bone marrow-derived mast cells (BMMC) have been used extensively as a mast cell model. BMMC, however, are immature cells that have no known physiological equivalent in tissues. They do not respond to IgG immune complexes. They may therefore not be appropriate for studying the physiopathology of IgE-induced allergies or IgG-induced tissue-specific inflammatory diseases which both depend on mature mast cells. Resident peritoneal mast cells are a minor population of differentiated cells that are not readily purified. They, however, can be expanded in culture to generate large numbers of homogeneous cells. We show here that these peritoneal cell-derived mast cells (PCMC) are mature serosal-type mouse mast cells which retain most morphological, phenotypic, and functional features of peritoneal mast cells. Like peritoneal mast cells, PCMC respond to IgG Abs. IgG immune complex-induced responses depended on FcgammaRIIIA and were negatively regulated by FcgammaRIIB. We found that a moderate FcgammaRIIB-dependent negative regulation, due not to a higher FcgammaRIIIA/FcgammaRIIB ratio, but to a relatively inefficient use of the lipid phosphatase SHIP1, determines this property of PCMC. PCMC also respond to IgE Abs. IgE-induced PCMC responses, however, differed quantitatively and qualitatively from BMMC responses. PCMC secreted no or much lower amounts of lipid mediators, chemokines, and cytokines, but they contained and released much higher amounts of preformed granular mediators. PCMC, but not BMMC, also contained and, upon degranulation, released molecules with a potent proteolytic activity. These properties make PCMC a useful new model for understanding the physiopathology of mast cells in IgE- and IgG-dependent tissue inflammation.

Rapamycin inhibits growth and survival of D816V-mutated c-kit mast cells.

Two classes of oncogenic mutations of the c-kit tyrosine kinase have been described: the juxtamembrane domain V560G mutation, which is preferentially found in gastrointestinal stromal tumors (GISTs), and the kinase domain D816V mutation, which is highly representative of systemic mastocytosis (SM). Here we show that both mutations constitutively activate the mammalian target of rapamycin (mTOR) signaling pathway. Surprisingly, the mTOR inhibitor rapamycin induces only apoptosis in HMC-1 cells bearing the D816V but not the V560G mutation. In support of this unexpected selectivity, rapamycin inhibits the phosphorylation of 4E-BP1, a downstream substrate of the mTOR pathway, but only in D816V HMC-1 cells. Importantly, D816V mast cells isolated from SM patients or from transgenic mice are sensitive to rapamycin whereas normal human or mouse mast cells are not. Thus, rapamycin inhibition appears specific to the D816V mutation. At present there is no effective cure for SM patients with the D816V mutation. The data presented here provide a rationale to test whether rapamycin could be a possible treatment for SM and other hematologic malignancies with the D816V mutation.

Establishment and characterization of a new human erythroleukemic cell line, ERY-1.

The growth factor-independent erythroleukemic cell line ERY-1 was established from the peripheral blood of a 87-year-old woman with chronic myeloid leukemia (CML) in the acute phase. Immunophenotyping showed that fresh leukemic cells were positive for CD13, CD33, CD36 and CD235a (glycophorin A), a phenotype compatible with that of erythroblastic cells. Cytogenetic and fluorescence in situ hybridization (FISH) analysis demonstrated classical t(9;22)(q34;q11) chromosomic translocation associated with a duplication of the BCR-ABL fusion gene. Other cytogenetic abnormalities were detected in all analyzed mitosis, the most frequent being a trisomy of chromosome 8. The established ERY-1 cell line retains these immunophenotypic and cytogenetic features, and light and electron microscopy confirmed the relatively mature erythroblastic phenotype of the cells. In addition, ERY-1 cell line expressed beta-globin mRNA and a non-phosphorylable form of the erythropoietin receptor, even in presence of erythropoietin. Of note, the proliferation of ERY-1 cells was inhibited by TGFbeta1 or STI-571 (Gleevec), without significant induction of further differentiation. In conclusion, ERY-1 is a new growth factor-independent human erythroleukemic cell line with a relatively mature phenotype that may be useful to study the molecular events involved in erythroblastic differentiation.

Identical abnormality of the short arm of chromosome 18 in two Philadelphia-positive chronic myelocytic leukemia patients with erythroblastic transformation, resulting in duplication of BCR-ABL1 fusion.

Two patients with Ph-positive chronic myelocytic leukemia in erythroblastic transformation and rearrangement of the short arm of chromosome 18 are reported. Fluorescence in situ hybridization studies showed that the 18p rearrangement resulted from translocation of the main part of chromosome 22 long arm to 18p, including BCR-ABL1 fusion. The 18p abnormality resulted, thus, in loss of 18p and duplication of BCR-ABL1 in both patients. The possible relation to the erythroblastic type of blastic phase is briefly discussed. In addition an apparently intact germline ABL1 gene was duplicated and inserted into chromosome 6 at band p21 in one of these patients.

Kit and c-kit mutations in mastocytosis: a short overview with special reference to novel molecular and diagnostic concepts.

Mastocytosis is a heterogeneous group of hematopoietic disorders characterized by abnormal growth and accumulation of mast cells (MC) in one or more organs. Clinical symptoms occur as a result of the release of chemical mediators and/or of pathologic infiltration of MC in various tissues. Although the initial events leading to mastocytosis have not yet been unraveled, acquired alterations in the c-kit gene coding for the receptor of stem cell factor (SCF), a major cytokine involved in MC growth, have been described in a significant number of patients. Of particular interest are point mutations resulting in a constitutively activated SCF receptor. Such mutations are probably involved in the abnormal (SCF-independent) proliferation of MC in these patients. New therapeutic strategies may be envisaged to inhibit the deregulated kinase activity of these mutant forms of c-kit.