Activity of chemotherapy in mucinous ovarian cancer with a recurrence free interval of more than 6 months: results from the SOCRATES retrospective study

<p>Abstract</p> <p>Background</p> <p>Mucinous ovarian carcinoma have a poorer prognosis compared with other histological subtypes. The aim of this study was to evaluate, retrospectively, the activity of chemotherapy in patients with platinum sensitive recurrent mucinous ovarian cancer.</p> <p>Methods</p> <p>The SOCRATES study retrospectively assessed the pattern of care of a cohort of patients with recurrent platinum-sensitive ovarian cancer observed in the years 2000–2002 in 37 Italian centres. Data were collected between April and September 2005. Patients with recurrent ovarian cancer with > 6 months of platinum free interval were considered eligible.</p> <p>Results</p> <p>Twenty patients with mucinous histotype and 388 patients with other histotypes were analyzed. At baseline, mucinous tumours differed from the others for an higher number of patients with lower tumor grading (p = 0.0056) and less advanced FIGO stage (p = 0.025). At time of recurrence, a statistically significant difference was found in performance status (worse in mucinous, p = 0.024). About 20% of patients underwent secondary cytoreduction in both groups, but a lower number of patients were optimally debulked in the mucinous group (p = 0.03). Patients with mucinous cancer received more frequently single agent platinum than platinum based-combination therapy or other non-platinum schedules as second line therapy (p = 0.026), with a response rate lower than in non-mucinous group (36.4% vs 62.6%, respectively, p = 0.04). Median time to progression and overall survival were worse for mucinous ovarian cancer. Finally, mucinous cancer received a lower number of chemotherapy lines (p = 0.0023).</p> <p>Conclusion</p> <p>This analysis shows that platinum sensitive mucinous ovarian cancer has a poor response to chemotherapy. Studies dedicated to this histological subgroup are needed.</p

Seasonal evolution unveils the internal structure of cometary nuclei

Remote sensing data of comets 9P/Tempel 1 and 67P/Churyumov-Gerasimenko (67P hereafter) indicate the occurrence of water-ice-rich spots on the surface of cometary nuclei [1-5]. These spots are up to tens of metres in size and appear brighter and bluer than the average surface at visible wavelengths. In addition, the extensive observation campaign performed by the Visible and InfraRed Thermal Imaging Spectrometer (VIRTIS, [6]) and the Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS, [7]) during the Rosetta escort phase at 67P revealed a seasonal cycle of the nucleus colour. This is characterised by blueing of the surface while approaching perihelion followed by progressive reddening and restoral of the original colour along the outbound orbit. The temporal evolution of the colour has been interpreted in previous studies as the result of increasing exposure of water ice at smaller heliocentric distances [8, 9], however, an explanation of such seasonal cycle in the context of a quantitative cometary activity model was not yet been provided. Recently, in [10] we showed that the seasonal colour cycle observed on comet 67P is determined by the occurrence of the above-mentioned water-ice-rich spots (referred to as Blue Patches - BPs -, given their colour). This can be explained in the context of activity models [11, 12] of pebble-made cometary nuclei [13], i.e. in terms of nucleus surface erosion induced by H2O and CO2 ices sublimation, driving the cometary activity. According to the scenario proposed in [10] (Fig. 1), the presence of the BPs is due to the exposure of subsurface sub-metre-sized Water-ice-Enriched Blocks (WEBs) thanks to surface erosion triggered by CO2 sublimation ejecting decimetre-sized chunks [12]. The WEBs are composed of ice-rich pebbles (dust-to-ice mass ratio δ=2, [14]), embedded in a matrix of drier pebbles (δ>>5) forming most of the nucleus. Once exposed to illumination as BPs, the WEBs are eroded by water-ice sublimation ejecting sub-cm dust [11]. By means of dedicated spectral and thermophysical modelling, we match the nucleus colour temporal evolution measured by the VIRTIS Mapping channel in the 0.55-0.8 µm spectral range. In doing this, we take into account the competing effects of CO2- and H2O-driven erosion that expose and remove the BPs, respectively, and are seasonally modulated by the insolation conditions, primarily depending on the heliocentric distance. The new nucleus model proposed in [10], implying an uneven distribution of water ice in cometary nuclei, reconciles the compositional dishomogeneities observed on comets (the BPs) at macroscopic (up to tens of metres) scale, with a structurally homogeneous pebble-made nucleus at small (centimetre) scale, and with the processes determining the cometary activity at microscopic (sub-pebble) scales. Figure 1. 67P surface gets bluer approaching perihelion as a consequence of the progressive exposure to sunlight of subsurface WEBs (from Figure 4 in Ciarniello et al., 2022, Nature Astronomy, https://doi.org/10.1038/s41550-022-01625-y). The comet nucleus is made of two types of pebbles, both including refractories and CO2 ice, with different water ice content: pebbles with high content of H2O ice form the WEBs, while H2O-ice-poor pebbles represent the rest of the nucleus. CO2 ice is stable beneath the CO2 sublimation front at depths >0.1 m [12]. Approaching perihelion, the CO2 ice sublimation rate increases, eroding the surface by chunk ejection and exposing the WEBs. Once exposed, WEBs lose CO2 and are observable as BPs. Water-ice sublimation erodes the BPs ejecting sub-cm dust from their surface and preventing the formation of a dry crust [11]. The BPs survive until their water-ice fraction is sublimated, producing the observed surface blueing. Please refer to ref. [10] for complete details. References [1] Sunshine, J. M. et al. (2006) Science 311, 1453-1455.[2] Filacchione, G. et al. (2016) Nature 529, 368-372.[3] Raponi, A. et al. (2016) Mon. Not. R. Astron. Soc. 462, S476-S490.[4] Barucci, M. A. et al. (2016) Astron. Astrophys. 595, A102.[5] Oklay, N. et al. (2017) Mon. Not. R. Astron. Soc. 469, S582-S597.[6] Coradini, A. et al. (2007) Space Sci. Rev. 128, 529-559.[7] Keller, H. U. et al. (2007) Space Sci. Rev. 128, 433-506.[8] Fornasier, S. et al. (2016) Science 354, 1566-1570.[9] Filacchione, G. et al. (2020) Nature 578, 49-52.[10] Ciarniello, M. et al. (2022) Nat. Astron. doi:10.1038/s41550-022-01625-y.[11] Fulle, M. et al. (2020) Mon. Not. R. Astron. Soc. 493, 4039-4044.[12] Gundlach, B. et al (2020). Mon. Not. R. Astron. Soc. 493, 3690-3715.[13] Blum, J. et al. (2017) Mon. Not. R. Astron. Soc. 469, S755-S77.[14] O'Rourke, L. et al. (2020) Nature 586, 697-701. Acknowledgements We thank the Italian Space Agency (ASI, Italy; ASI-INAF agreements I/032/05/0 and I/024/12/0), Centre National d'Etudes Spatiales (CNES, France), and Deutsches Zentrum für Luft-und Raumfahrt (DLR, Germany) for supporting this work. VIRTIS was built by a consortium from Italy, France and Germany, under the scientific responsibility of IAPS, Istituto di Astrofisica e Planetologia Spaziali of INAF, Rome, which also led the scientific operations. The VIRTIS instrument development for ESA has been funded and managed by ASI (Italy), with contributions from Observatoire de Meudon (France) financed by CNES and from DLR (Germany). The VIRTIS instrument industrial prime contractor was former Officine Galileo, now Leonardo Company, in Campi Bisenzio, Florence, Italy. Part of this research was supported by the ESA Express Procurement (EXPRO) RFP for IPL-PSS/JD/190.2016. D.K. acknowledges DFG-grant KA 3757/2-1. This work was supported by the International Space Science Institute (ISSI) through the ISSI International Team "Characterization of cometary activity of 67P/Churyumov-Gerasimenko comet". This research has made use of NASA's Astrophysics Data System

Wolbachia-Mediated Male Killing Is Associated with Defective Chromatin Remodeling

Male killing, induced by different bacterial taxa of maternally inherited microorganisms, resulting in highly distorted female-biased sex-ratios, is a common phenomenon among arthropods. Some strains of the endosymbiont bacteria Wolbachia have been shown to induce this phenotype in particular insect hosts. High altitude populations of Drosophila bifasciata infected with Wolbachia show selective male killing during embryonic development. However, since this was first reported, circa 60 years ago, the interaction between Wolbachia and its host has remained unclear. Herein we show that D. bifasciata male embryos display defective chromatin remodeling, improper chromatid segregation and chromosome bridging, as well as abnormal mitotic spindles and gradual loss of their centrosomes. These defects occur at different times in the early development of male embryos leading to death during early nuclear division cycles or large defective areas of the cellular blastoderm, culminating in abnormal embryos that die before eclosion. We propose that Wolbachia affects the development of male embryos by specifically targeting male chromatin remodeling and thus disturbing mitotic spindle assembly and chromosome behavior. These are the first observations that demonstrate fundamental aspects of the cytological mechanism of male killing and represent a solid base for further molecular studies of this phenomenon

Effect of vitamin D3 seasonal supplementation with 1500 IU/day in north Italian children (DINOS study)

Abstract Background The appropriate dose of vitamin D supplementation in children is still debated. We calculated that the recommended dose of 600–1000 IU vitamin D3/day is not sufficient to reach a serum 25-hydroxyvitamin D (25-OH-D) level of at least 30 ng/ml (75 nmol/l) in north Italian children > 12 months. The aim of this study was to analyse the effect of seasonal supplementation with 1500 IU (=37.5 μg) vitamin D3/day. Methods DINOS (D-vitamIN Oral Supplementation) study was a pilot, monocentric, non-random case-control register study. It was conducted in a paediatric primary care setting near Padova (North Italy, 45°N latitude). The data of 203 children (girls:boys 1:1,33) aged 2–15 years, collected between November 2010 and January 2015, were analysed. Active group A (n = 82) were given 1500 IU vitamin D3/day from November to April; control Group B (n = 121) received no supplementation. The serum 25-OH-D test was part of a laboratory tests panel and performed using a chemiluminescence immunoassay method. Results Serum 25-OH-D mean level + standard deviation throughout the period was 32 + 13 ng/ml (80 + 32 nmol/l) in group A vs 22 + 10 ng/ml (55 + 25 nmol/l) in group B. In group A 12% had vitamin D deficiency 25-OH-D < 20 ng/ml (50 nmol/l) and 1.2% severe vitamin D deficiency 25-OH-D < 10 ng/ml (25 nmol/l). In group B 46% had vitamin D deficiency and 9% severe deficiency (P <  0.001). In group A mean levels were normal or near-normal all the year except in May. Group B reached mean 25-OH-D levels close to 30 ng/ml (75 nmol/l) only in late summer. The active group mean 25-OH-D level was normal in preschoolers and schoolers but not in adolescents. Non-white children had a three-times vitamin D deficiency probability despite supplementation. Conclusions Vitamin D supplementation with at least 1500 IU vitamin D3/day from November to April was found appropriate for children in North Italy. A prolongation until May could be useful. Higher doses and/or prolonged periods could be more appropriate especially in adolescents and in non-white children. Study registration DINOS gained the approval of Padova Ethics Committee (n. 3960/U16/2016)

Home non-invasive mechanical ventilation and long-term oxygen therapy in stable hypercapnic chronic obstructive pulmonary disease patients: comparison of costs.

BACKGROUND: A cost analysis of nocturnal non-invasive ventilation (NNV) in stable chronic obstructive pulmonary disease (COPD) patients would be helpful in decision making, when the balance between the increased demand and the availability of resources should be checked. OBJECTIVES: Based on data from the Italian trial in stable hypercapnic COPD patients, this study compares the cost of care associated with the use of NNV when added to the usual long-term oxygen therapy (LTOT) with the cost of care of LTOT regimen alone. METHODS: Cost was calculated in 77 of 90 patients included into that trial. Analysis included drug therapy, hospitalisations due to acute exacerbation, oxygen and ventilator equipment. An estimation of charges was made according to the national sources of cost for drugs and hospital admissions and the actualised reimbursement for the home care provided to both oxygen and ventilator users. The cost/day comparison was made between the individual patients in the 2 groups (NNV + LTOT, n = 35; LTOT, n = 42). RESULTS: The mean cost of drugs and oxygen was similar in both groups, whereas the cost of hospitalisation tended to be lower in NNV + LTOT compared to LTOT alone (8.25 +/-10.29 vs. 12.50 +/- 20.28 EUR/patient/day, p < 0.05). Inclusion of the ventilator equipment increased the total cost to 23.73 EUR/day in the NNV + LTOT compared to 21.42 EUR/day in the LTOT group (not significant). CONCLUSIONS: The present report suggests that long-term management with addition of non-invasive ventilation does not increase costs compared with the usual LTOT regimen: the hospital-related costs were reduced when using the ventilator in these hypercapnic COPD patients