Safety of Rapid Daratumumab Infusion: A Retrospective, Multicenter, Real-Life Analysis on 134 Patients With Multiple Myeloma

Background: The anti-CD38 monoclonal antibody daratumumab is the backbone of most anti-multiple myeloma (MM) regimens. To mitigate the risk of infusion-related reactions (IRRs), intravenous daratumumab administration requires 7 hours for the first infusion and 3.5-4 hours thereafter, thus making daratumumab-containing regimens burdensome for patients and health care resources. Preliminary data suggest that a rapid (90-minute) infusion of daratumumab is safe and does not increase IRRs. The rapid schedule was adopted by our centers since 2019. Methods: We conducted an observational multi-center, real-life study to assess the safety of rapid daratumumab infusion protocol from the third administration in relapsed MM patients receiving daratumumab alone or in combination with lenalidomide-dexamethasone or bortezomib-dexamethasone. The primary endpoint was the safety of the rapid infusion protocol, particularly in terms of IRRs. Results: A total of 134 MM patients were enrolled. IRRs occurred in 7 (5%) patients and were mostly mild (6/7 of grade 1-2), with only 1 patient experiencing a grade 3 IRR. Due to the IRRs, 5 (3.7%) patients discontinued the rapid infusions and resumed daratumumab at the standard infusion rate, while 1 patient permanently discontinued daratumumab. In 4/7 patients (57%), IRRs occurred while resuming rapid daratumumab infusions after a temporary interruption (2-4 months). No other adverse event was considered related to the rapid infusion protocol. Conclusions: Our findings confirmed the safety of rapid daratumumab infusions starting from the third administration. In case of prolonged daratumumab interruption, it is advisable to resume infusions at the standard rate (3.5 hours) before switching to the rapid infusion

Geological and Hydrogeological Characterization of Springs in a DSGSD Context (Rodoretto Valley – NW Italian Alps)

As continuous groundwater monitoring in the upper sector of Rodoretto Valley (Germanasca Valley, Italian Western Alps) is hampered by logistical problem of data collection during winter and spring months, the only tools currently available to derive hydrogeological information are non-continuous and non-long-term dataset of spring discharge (Q), temperature (T) and electrical conductivity (EC). In order to quantity aquifer groundwater reserve, available Q dataset of a small mountain spring (Spring 1 CB) was investigated by applying the analytical solutions developed by Boussinesq (J Math Pure Appl 10:5–78, 1904) and Maillet (Essais dı’hydraulique souterraine et fluviale, vol 1. Herman et Cie, Paris, 1905); T and EC datasets were also used to provide qualitative information about the nature of the aquifer that supplies the spring. The outcomes of the elaborations highlighted the limits of applicability of these methods in the presence of a non-continuous Q dataset: both Boussinesq (J Math Pure Appl 10:5–78, 1904) and Maillet (Essais dı’hydraulique souterraine et fluviale, vol 1. Herman et Cie, Paris, 1905) estimated that discharge values as a function of recession time were found to be consistently lower than the available discharge ones and the estimated groundwater volumes stored over time above the spring level turned out to be underestimated. Continuous (hourly value) and long-term Q, EC and T values are, therefore, needful to correctly quantify and to make a proper management of groundwater resources in mountain areas

Frontal networks in adults with autism spectrum disorder.

It has been postulated that autism spectrum disorder is underpinned by an 'atypical connectivity' involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism spectrum disorder and 61 neurotypical controls, using two complementary approaches to diffusion tensor magnetic resonance imaging. First, we applied tract-based spatial statistics, a 'whole brain' non-hypothesis driven method, to identify differences in white matter networks in adults with autism spectrum disorder. Following this we used a tract-specific analysis, based on tractography, to carry out a more detailed analysis of individual tracts identified by tract-based spatial statistics. Finally, within the autism spectrum disorder group, we studied the relationship between diffusion measures and autistic symptom severity. Tract-based spatial statistics revealed that autism spectrum disorder was associated with significantly reduced fractional anisotropy in regions that included frontal lobe pathways. Tractography analysis of these specific pathways showed increased mean and perpendicular diffusivity, and reduced number of streamlines in the anterior and long segments of the arcuate fasciculus, cingulum and uncinate--predominantly in the left hemisphere. Abnormalities were also evident in the anterior portions of the corpus callosum connecting left and right frontal lobes. The degree of microstructural alteration of the arcuate and uncinate fasciculi was associated with severity of symptoms in language and social reciprocity in childhood. Our results indicated that autism spectrum disorder is a developmental condition associated with abnormal connectivity of the frontal lobes. Furthermore our findings showed that male adults with autism spectrum disorder have regional differences in brain anatomy, which correlate with specific aspects of autistic symptoms. Overall these results suggest that autism spectrum disorder is a condition linked to aberrant developmental trajectories of the frontal networks that persist in adult life

Ab Inito Calculations on Possible Hard Materials Based on Interpenetrating Networks: SiO2.BeF2

The energetics and electronic behavior of SiO2\ub7BeF2, based on interpenetrating diamondoid nets and recently proposed as a possible hard material, have been studied with ab initio periodic LCAO Hartree-Fock methods. The composite compound turns out to be unstable with respect to the precursors SiO2 and BeF2. The origin of the instability has been analyzed with the aid of crystal orbital displacement (COD) plots. A bulk modulus close to the sum of those of the two precursors is calculated for SiO2\ub7BeF2. The additivity of the bulk moduli of subnets suggests that hard precursors should be required to obtain superhard materials

Modelling a fifth-generation bidirectional low temperature district heating and cooling (5GDHC) network for nearly Zero Energy District (nZED)

Current sustainability challenges place entire communities at the centre of the energy revolution, rather than individual buildings. The need to develop energy-efficient and low-carbon economies lies at the heart of fifth-generation district heating and cooling (5GDHC) networks. The potential of these networks is represented by a lower working temperature close to the ground temperature, usually between 10 and 25 °C. Thanks to this feature, the network presents optimal conditions to be used as a heat source for reversible heat pumps. 5GDHC networks provide users with a fundamental active role, giving the possibility of extracting and releasing energy into the thermal network, while producing heating and cooling simultaneously. The integration of renewable sources and reduced heat losses are added values to be taken into consideration. Given the limited application of 5GDHC networks, this paper aims to evaluate the energy advantages of coupling several users within a bidirectional fifth-generation network based on the integration of reversible heat pumps with on-site production by renewable sources and waste energy recovery. An integrated model of 5GDHC network with buildings was developed in order to meet the energy needs of a neighbourhood made up of users with different energy profiles throughout a whole year. To enhance future applications, the energy performance of the 5GDHC network model was studied through a simulation tool. An hourly numerical calculation tool was developed to simulate the behaviour of the network and the users’ response over an annual period, estimating the energy shared between users during both the heating and cooling seasons. The results obtained are presented not only in terms of energy exchanged in the network, but also in the form of performance indexes of the individual users, identifying advantageous combinations between the users for future design developments of these systems. The outcomes of this paper highlight the integration of established technologies into fifth-generation thermal networks, with a view to a future development of nearly Zero Energy Districts (nZED)