Hypersensitivity reactions (HSRs) to platinum are an important issue in the treatment of patients (pts) with ovarian cancer (OC). Germline BRCA mutations have been proposed as a risk factor. We aimed ...at evaluating the incidence and severity of HSRs to platinum in OC pts. with known BRCA status.
We retrospectively analyzed 432 pts. from 5 Italian Centers. In addition, we performed a systematic review and meta-analysis of published series.
Four hundred nine pts. received at least one prior platinum-based treatment line: 314 were BRCA wild type (77%) and 95 were BRCA mutated (23%). There was no statistical difference in exposure to platinum. Incidence of any grade HSRs was higher among BRCA mutated pts. 9% vs 18%, p = 0.019 and the time-to-HSRs curves show that the risk increases with the duration of platinum exposure, in BRCA mutated pts. more than in BRCA wild type. A multivariable analysis showed that harboring a germline BRCA mutation was related to a higher incidence of HSRs (HR: 1.84, 95% CI 1.00–3.99, p = 0.05) while having received pegylated liposomal doxorubicin (PLD) was related to a lower incidence of HSRs (HR: 0.03 95% CI 0.004–0.22, p = 0.001). The systematic review confirmed the higher incidence of HSRs in BRCA mutated pts., though heterogeneity among series was significant.
In OC pts. with BRCA mutations, there is a significantly higher incidence of HSRs to carboplatin, not justified by longer drug exposure. On the other hand, PLD exerted a protective role in our series.
•Hypersensitivity reactions (HSRs) to carboplatin are frequent in pretreated ovarian cancer (OC) patients (pts).•The role of BRCA mutations (mut) as a risk factor has been suggested.•We demonstrate that BRCAmut pts. have an increased risk of HSRs which is not justified by longer drug exposure only.•Receiving pegylated liposomal doxorubicin was a protective factor in our series.•The meta-analysis of literature, though results are heterogeneous, confirms the role of BRCAmut in increasing HSRs risk.
A kinetic model has been developed to describe the growth of single-walled carbon nanotubes (SWNT) in the CoMoCAT method, which is based on the disproportionation of CO on supported CoMo catalysts. ...The model attempts to capture mathematically the different stages involved in this method: (i) catalyst activation or in-situ creation of active sites, i.e., reduced Co clusters by transformation of CoMoOx precursor species, or oxidized sites; (ii) CO decomposition over active sites, which increases the surface fugacity of carbon until reaching a certain threshold; (iii) nucleation of ordered forms of carbon; (iv) C diffusion (both across the surface and into the metal particle); (v) SWNT growth; (vi) termination, by either deactivation of the catalyst active sites or by increase in the carbon concentration at the metal/SWNT interface, approaching that of the metal/gas interface and eliminating the driving force for diffusion. Previous investigations have only explained the growth termination by the former. Here, we emphasize the possible contribution of the later and propose a novel "hindrance factor" to quantify the effect of nanotube interaction with its surroundings on the growth termination. To test the kinetic model and obtain typical values of the physical parameters, experiments have been conducted on a CoMo/SiO2 catalyst in a laboratory flow reactor, in which the rate of carbon deposition was continuously evaluated by the direct measurement of the CO2 evolution as a function of time. The experimental data are fitted very well with model.
Background: The complexity of myeloproliferative neoplasms (MPNs) cannot be characterized by acquired somatic mutations alone. Individual genetic background is thought to contribute to the ...development of MPNs. The aim of our study was to assess the association between the TET2 rs1548483 single nucleotide polymorphism (SNP) and the susceptibility to polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) or chronic myeloid leukemia (CML). Methods: We evaluated the TET2 rs1548483 SNP through real-time PCR in 1601 MPN patients out of which 431 with PV, 688 with TE, 233 with PMF, 249 with CML and 197 controls. We included only patients with a molecularly proven driver mutation, such as JAK2 V617F, CALR or BCR-ABL1. Results: Significant association between TET2 rs154843 variant allele and JAK2 V617F-positive PV and PMF (OR = 1.70; 95% CI: 1.01–2.91; p-value = 0.046, and OR = 2.04; 95% CI: 1.10–3.77; p-value = 0.024, respectively), and type 2 CALR-positive PMF (OR = 2.98; 95% CI: 1.12–7.93; p-value = 0.035) was noted. Conclusions: The TET2 rs1548483 SNP is associated with the susceptibility to molecularly annotated PV and PMF.
The oligophrenin-1 (OPHN1) gene, localized on the X chromosome, is a Rho-GTPase activating protein that is related to syndromic X-linked intellectual disability (XLID). XLID, characterized by brain ...anomalies, namely cerebellar hypoplasia, specific facial features, and intellectual disability, is produced by different mutations in the OPHN1 gene.
In this report, we present the clinical and molecular findings of a family affected by a mild XLID due to a deletion in the OPHN1 gene, exon 21, Xq12 region using Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. The clinical features present in the family are a mild developmental delay, behavioral disturbances, facial dysmorphism, pes planus, nystagmus, strabismus, epilepsy, and occipital arachnoid cyst.
The MLPA analysis was performed for investigation of the copy number variations within the X chromosome for the family.
The MLPA analysis detected a deletion in the OPHN1 gene, exon 21 for the proband, and a heterozygous deletion for the probands mother. The deletion of the Xq12 region of maternal origin, including the exon 21 of the OPHN1 gene, confirmed for the probands nephew.
Our findings emphasize the utility of the MLPA analysis to identify deletions in the OPHN1 gene responsible for syndromic XLID. Therefore, we suggest that MLPA analysis should be performed as an alternative diagnostic test for all patients with a mild intellectual disability associated or not with behavioral disturbances, facial dysmorphism, and brain anomalies.
Simulations of two heavy rainfall events south of the Alps have been conducted with a non-hydrostatic model at horizontal resolutions ranging from 40 to 2.5 km. Emphasis is placed on the assessment ...of two recent model developments: a detailed explicit mixed phase microphysical scheme and a two-way interactive grid nesting method. In the high-resolution simulations, the impact of the ice phase was found to be quite substantial, accelerating the propagation of the surface front and modifying the spatial distribution of the rainfall. Simulations carried out with two-way interactive grid nesting yielded more realistic overall precipitation patterns, particularly at the finest horizontal resolution.
In the framework of the RAPHAEL EU project, a series of past heavy precipitation events has been simulated with different meteorological models. Rainfall hindcasts and forecasts have been produced by ...four models in use at various meteorological services or research centres of Italy, Canada, France and Switzerland. The paper is focused on the comparison of the computed precipitation fields with the available surface observations. The comparison is carried out for three meteorological situations which lead to severe flashflood over the Toce-Ticino catchment in Italy (6599 km2) or the Ammer catchment (709 km2) in Germany. The results show that all four models reproduced the occurrence of these heavy precipitation events. The accuracy of the computed precipitation appears to be more case-dependent than model-dependent. The sensitivity of the computed rainfall to the boundary conditions (hindcast v. forecast) was found to be rather weak, indicating that a flood forecasting system based upon a numerical meteo-hydrological simulation could be feasible in an operational context. Keywords: meteorological models, precipitation forecast
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