Anti-BCMA novel therapies for multiple myeloma

Recent advances in multiple myeloma therapy have increased the depth of response and ultimately survivals; however, the prognosis remains poor. The BCMA antigen is highly expressed in myeloma cells, thus representing a target for novel therapies. Several agents that target BCMA through different mechanisms, including bispecific T cell engagers drug conjugated to antibody and CAR-T cells, are now available or under development. Immunotherapies targeting BCMA have shown good results in efficacy and safety in multiple myeloma patients previously treated with several lines of therapy. This review will discuss the recent development of anti-BCMA targeted treatments in myeloma, with a special focus on currently available agents

Critical appraisal of the role of volumetric modulated arc therapy in the radiation therapy management of breast cancer

Background: The aim of this review is the critical appraisal of the current use of volumetric modulated arc therapy for the radiation therapy management of breast cancer. Both clinical and treatment planning studies were investigated. Material and methods: A Pubmed/MEDLINE search of the National Library of Medicine was performed to identify VMAT and breast related articles. After a first order rejection of the irrelevant findings, the remaining articles were grouped according to two main categories: clinical vs. planning studies and to some sub-categories (pointing to significant technical features). Main areas of application, dosimetric and clinical findings as well as areas of innovations were defined. Results: A total of 131 articles were identified and of these, 67 passed a first order selection. Six studies reported clinical results while 61 treatment dealed with treatment planning investigations. Among the innovation lines, the use of high intensity photon beams (flattening filter free), altered fractionation schemes (simultaneous integrated boost, accelerated partial breast irradiation, single fraction), prone positioning and modification of standard VMAT (use of dynamic trajectories or hybrid VMAT methods) resulted among the main relevant fields of interest. Approximately 10% of the publications reported upon respiratory gating in conjunction with VMAT. Conclusions: The role of VMAT in the radiation treatment of breast cancer seems to be consolidated in the in-silico arena while still limited evidence and only one phase II trial appeared in literature from the clinical viewpoint. More clinical reports are needed to fully proove the expected dosimetric benefits demonstrated in the planning investigations

P54 Incidence of skin cancer in systemic lupus erythematosus compared with systemic sclerosis and general population

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The WEST Study: A Retrospective and Multicentric Study on the Impact of Steroid Therapy in West Nile Encephalitis

Background: The use of steroid therapy in potentially life-threatening neuroinvasive forms of West Nile infection (WNND) is controversial. The aim of this study is to assess the efficacy of steroid therapy in reducing intrahospital mortality, length of stay, and neurological sequelae at discharge. Methods: This was a multicenter, retrospective, observational study conducted in 5 hospitals in Northern Italy, headed by the Fondazione IRCSS Policlinico San Matteo (Pavia). We extracted all patient data with WNND diagnoses, comparing patients who received steroid treatment with patients who did not receive steroid treatment between January 2014 and January 2022. Comparisons between the 2 groups were performed using chi-square tests for categorical variables and Mann-Whitney tests for non-normal continuous data, and a generalized linear model for the binomial family was carried out. Results: Data from 65 WNND patients were extracted. Among these patients, 33 (50.7%) received steroid therapy at any point during their hospitalization. Receiving steroid therapy did not significantly reduce intrahospital mortality (odds ratio [OR], 1.70; 95% CI, 0.3-13.8; P = .89) or neurological sequelae at discharge (OR, 0.53; 95% CI, 0.16-1.76; P = .47). Conclusions: Steroid treatment is currently used on a single-case basis in severe WNND. More prospective data are needed to demonstrate a protective effect on mortality and neurological sequelae

3D groundwater flow and deformation modelling of Madrid aquifer

A novel methodological approach to calibrate and validate three-dimensional (3D) finite element (FE) groundwater flow and geomechanical models has been implemented using Advanced Differential Interferometric SAR (A-DInSAR) data. In particular, we show how A-DInSAR data can be effectively used to (1) constrain the model set-up in evaluating the areal influence of the wellfield and (2) characterise the aquifer system, specifically the storage coefficient values, which represents a fundamental step in managing groundwater resources. The procedure has been tested to reconstruct the surface vertical and horizontal movements caused by the Manzanares-Jarama wellfield located northwest of Madrid (Spain). The wellfield was used to supply freshwater during major droughts over the period between 1994 and 2010. Previous A-DInSAR outcomes obtained by ERS-1/2 and ENVISAT acquisitions clearly revealed the seasonality of the land displacements associated to the withdrawal and recovery cycles that characterized the wellfield development. A time-lag of about one month, which is in the order of the time span between two SAR acquisitions, between the hydraulic head changes and the displacements has been detected in this site by a wavelet analysis of A-DInSAR and piezometer time series. The negligible delay between the forcing factor and the system response and the complete subsidence recovery when piezometric head recovers supported the understanding of a minor role played by the pore pressure propagation within clay layers and the almost perfectly elastic behavior of the system (viscosity is negligible), respectively. The developed geomechanical model satisfactorily reproduces the pumping-induced deformations with a Root Mean Square Error (RMSE) between observed and simulated land displacements in the order of 0.1-0.3 mm. The results give insights about the approach benefits in deeply understanding the spatio-temporal aquifer-system response to the management of this strategic water resource for Madrid.The activity has been developed within the scientific collaboration established in the framework of the UNESCO Land Subsidence International Initiative (LaSII - https://www.landsubsidence-unesco.org/). The research was funded by University of Pavia in the framework of a research grant award “assegno di tipo A premiale” for research activities at the Dept. of Earth and Environmental Sciences, within the research project entitled “Sustainable groundwater resources management by integrating A-DInSAR derived monitoring and flow modeling results” assigned to Roberta Bonì in March 2019. This research was partially funded by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO), the State Agency of Research (AEI), and the European Funds for Regional Development (FEDER) under project TEC2017-85244-C2-1-P

Understanding the dynamic behaviour for the Madrid aquifer (Spain): insights from the integration of A-DInSAR and 3-D groundwater flow and geomechanical models

Advanced Differential Interferometric Synthetic Aperture Radar (A-DInSAR) techniques and 3-D groundwater flow and geomechanical models are integrated to improve our knowledge about the Tertiary detritic aquifer of Madrid (TDAM). In particular, the attention is focused on the Manzanares-Jarama well field, located to the northwest of Madrid, which experienced five cycles of extensive groundwater withdrawal followed by natural recovery, to cope with the droughts occurred in summer 1995, 1999, 2002, 2006, and 2009. Piezometric records and A-DInSAR data acquired by ERS-1/2 and ENVISAT satellites during the periods 1992–2000 and 2002–2010, respectively, have been used to calibrate the groundwater flow and the geomechanical models. A time-lag of about one month between the hydraulic head changes and the displacements of the land surface has been detected by a joint wavelet analysis of A-DInSAR and piezometer head time series. Overall, the results show the effectiveness of the proposed integrated approach composed of A-DInSAR and 3-D geomechanical model to characterize the aquifer-system response during and after the groundwater withdrawal.This research has been supported by the Università degli Studi di Pavia (Assegno di tipo A premiale: “Sustainable groundwater resources management by integrating A-DInSAR derived monitoring and flow modeling results” assigned to Roberta Bonì in March 2019) and the Spanish Ministry of Economy, Industry and Competitiveness (MINECO), the State Agency of Research (AEI), and the European Funds for Regional Development (FEDER) (grant no. TEC2017-85244-C2-1-P)

Wavelet analysis of land subsidence time-series: Madrid Tertiary aquifer case study

Interpretation of land subsidence time-series to understand the evolution of the phenomenon and the existing relationships between triggers and measured displacements is a great challenge. Continuous wavelet transform (CWT) is a powerful signal processing method mainly suitable for the analysis of individual nonstationary time-series. CWT expands time-series into the time-frequency space allowing identification of localized nonstationary periodicities. Complementarily, Cross Wavelet Transform (XWT) and Wavelet Coherence (WTC) methods allow the comparison of two time-series that may be expected to be related in order to identify regions in the time-frequency domain that exhibit large common cross-power and wavelet coherence, respectively, and therefore are evocative of causality. In this work we use CWT, XWT and WTC to analyze piezometric and InSAR (interferometric synthetic aperture radar) time-series from the Tertiary aquifer of Madrid (Spain) to illustrate their capabilities for interpreting land subsidence and piezometric time-series information.This research has been supported by the Spanish Ministry of Economy and Competitiveness, the State Agency of Research and the European Funds for Regional Development (grant no. TEC2017-85244-C2-1-P)