47 research outputs found

    Rationale and evidence on the use of tocilizumab in COVID-19: a systematic review

    Get PDF
    Background: Tocilizumab is an IL-6 receptor-blocking agent proposed for the treatment of severe COVID-19. The aim of this systematic review was to describe the rationale for the use of tocilizumab for the treatment of COVID-19 and to summarize the available evidence regarding its efficacy and safety. Methods: MEDLINE, PubMed, EMBASE, pre-print repositories (bioRxiv and medRxiv) and two trial Registries were searched for studies on the use of tocilizumab in COVID-19 or SARS-CoV-2 infection, viral pneumonia, and/or sepsis until 20th June 2020. Results: We identified 3 indirect pre-clinical studies and 28 clinical studies including 5776 patients with COVID-19 (13 with a comparison group, 15 single-arm). To date, no randomized trials have been published. We retrieved no studies at low risk of bias. Forty-five ongoing studies were retrieved from trial registries. Conclusions: There is insufficient evidence regarding the clinical efficacy and safety of tocilizumab in patients with COVID-19. Its use should be considered experimental, requiring ethical approval and clinical trial oversight

    Farnesyltransferase inhibitors and human malignant pleural mesothelioma: a first-step comparative translational study.

    Get PDF
    It is known that the potential clinical use of farnesyltransferase inhibitors (FTI) could be expanded to include cancers harboring activated receptor tyrosine kinases. Approximately 70% of malignant pleural mesotheliomas (MPM) overexpress epidermal growth factor receptors (EGFR) and a subset express both EGFR and transforming growth factor A (TGF-A), suggesting an autocrine role for EGFR in MPM. We checked on MPM cells (10 human cell lines, 11 primary cultures obtained by human biopsies, and 7 short-term normal mesothelial cell cultures) concerning the following: (a) the relative overexpression of EGFR (Western blotting, flow cytometry, immunohistochemistry), (b) the relative expression of EGFR ligands (EGF, amphiregulin, TGF-A, ELISA), (c) the relative increase of the activated form of Ras (Ras-bound GTP) after EGF stimulation (Ras activation assay), (d) the efficacy of five different FTIs (HDJ2 prenylation, cell cytotoxicity, and apoptosis using ApopTag and gel ladder). EGFR was overexpressed in MPM cells compared with normal pleural mesothelial cells in equivalent levels as in non\u2013small cell lung cancer cells A549. MPM cells constitutively expressed EGFR ligands; however, Ras activation was attenuated at high EGF concentrations (100 ng/mL). Growth of MPM cells was substantially not affected by treatment with different FTIs (SCH66336, BMS- 214662, R115777, RPR-115135, and Manumycin). Among these, BMS-214662 was the only one moderately active. BMS-214662 triggered apoptosis in a small fraction of cells (not higher than 30%) that was paralleled by a slight decrease in the levels of TGF-A secreted by treated MPM cells. Our data highlighted the concept that the same signaling pathway can be regulated in different ways and these regulations can differ between different cells of different origin

    Surgical treatment in patient with non-small-cell lung cancer with fissure involvement: Anatomical versus nonanatomical resection

    Get PDF
    OBJECTIVE: Despite the intense debate concerning the prognostic impact of fissure involvement (FI) in patients with non-small-cell lung cancer, no specific surgical strategies have been yet recommended when this condition occurs. In this setting, we report our monocentric 10-years experience to investigate this issue. METHODS: From January 2000 to January 2010, the clinical data of 40 non-small-cell lung cancer patients with FI undergoing curative resection were retrospectively reviewed. The sample was stratified according to the type of resection: group A (28 patients): anatomical resection (bilobectomy [21 patients], pneumonectomy [7 patients]); group B (12 patients): nonanatomical resection (lobectomy plus wedge resection [LWR]). The end-points were (1) impact of different surgical approach on the pulmonary function (measured before surgery and 1 month after discharge); (2) disease-specific survival; and (3) tumor recurrence.The t test, χ, and log-rank tests, Kaplan-Meier method, and Cox and logistic regression analyses were used for the statistical analysis. RESULTS: No differences between the two groups were found when comparing the clinical characteristics, histology, pN or pT status, p-stage, residual (R1) disease, tumor grading, or tumor size. Similarly, the baseline preoperative function (tested as forced expiratory volume in 1 second-%-predicted, FEV1%) was likewise comparable (92.5% ± 21.0% in group A versus 85.2% ± 20.0% in group B; p = not significant). The decline of FEV1% after surgery was slightly higher in group A (-24.9% ± 13.5%) when compared with that in group B (-19.5% ± 13.3%), but this difference was not statistically significant (p = ns). Nevertheless, the 5-year disease-specific survival was 56% for group A and 47% for group B (p = ns). The recurrence rate did not differ between the patients undergoing a LWR (3 of 12 patients) and those undergoing a bilobectomy or pneumonectomy (9 of 28 patients) (p = ns). The presence of FI extended for more than 3 cm was found to be the most significant prognostic factor when analyzing survival (p = 0.002) and recurrence rate (p< 0.001). CONCLUSIONS: Our results suggest that nonanatomical resection (LWR) could be considered as a feasible surgical option (especially in "frail" patients with an extent of FI less than 3 cm) in the light of the similar oncological and functional outcome compared with anatomical resection. Further studies based on larger series are needed to confirm these preliminary data and also to investigate the impact on the postoperative quality of life

    Randomized trial of thymectomy in myasthenia gravis

    Get PDF

    What is the best way to diagnose and stage malignant pleural mesothelioma?

    No full text

    Surface nanostructuring and optical activation of lithium fluoride crystals by ion beam irradiation

    No full text
    We present results on simultaneous nanostructuring and optical activation of lithium fluoride crystals by 800 eV off-normal Ar+ sputtering at different ion doses. The samples were studied by atomic force microscopy and optical spectroscopy. After ion irradiation smoothening of the initial random roughness is achieved and well-defined self-organized ripple structures appear, having a mean periodicity of 30 nm and a mean height of 3 nm. The simultaneous optical activation of the irradiated samples is due to the stable formation of electronic defects with intense photoluminescence in the visible spectral range. These results demonstrate the possibility to simultaneously modify the optical and topographical properties of LiF crystals by off-normal ion irradiation. Though none of the usual optical measuring devices have the required resolution to study the spatial distribution of the produced electronic defects, therefore allowing us to collect information on the possible \u201coptical nanostructuring\u201d of the irradiated surface, the efficient production of color centers with intense and stable photoluminescence in the visible spectral range on the periodically nanostructured surface seems anyhow very promising for the production of advanced substrates. Our findings seem to indicate that further work could be successfully done to obtain, in a controlled way, functionalized substrates with regular patterns of lithiumenriched and light-emitting areas at the nanoscale level
    corecore