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  • 1
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 17 ( 2021-08-26), p. 3834-
    Abstract: Background: Total body irradiation (TBI) is a mandatory step for patients with acute lymphoblastic leukemia (ALL), undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In the past, amylases have been reported to be a possible sign of TBI toxicity. We investigated the relationship between total amylases (TA) and transplant-related outcomes in pediatric recipients. Methods: We retrospectively analyzed the medical records of all the patients who underwent allogeneic HSCT between January 2000 and November 2019. The inclusion criteria were the following: recipient’s age between 2 and 18, diagnosis of ALL, no previous transplantation, and use of TBI-based conditioning. The serum total amylase and pancreatic amylase were evaluated before, during, and after transplantation. Cytokines and chemokines assays were retrospectively performed. Results: 78 patients fulfilled the inclusion criteria. Fifty-seven patients were treated with fractionated TBI, and 21 with a single-dose regimen. The overall survival (OS) was 62.8%. Elevated values of TA were detected in 71 patients (91%). The TA were excellent in predicting the OS (AUC = 0.773; 95% CI = 0.66–0.86; p 〈 0.001). TA values below 374 U/L were correlated with a higher OS. The highest mean TA values (673 U/L) were associated with a high disease-progression mortality rate. The TA showed a high predictive performance for disease progression-related death (AUC = 0.865; 95% CI = 0.77–0.93; p 〈 0.0001). Elevated TA values were also connected with significantly higher levels of proinflammatory cytokines, such as TNF-α, IL-6, and RANTES (p 〈 0.001). Conclusions: this study shows that TA is a valuable predictor of post-transplant OS and increased risk of leukemia relapse.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 2
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 2 ( 2023-01-16), p. 730-
    Abstract: The use of anti-thymocyte globulin (ATG) as part of conditioning to prevent graft-versus-host disease (GVHD) may severely impair immune reconstitution (IR). We analyzed relationships between ATG exposure, the recipient lymphocyte count, IR, and transplant outcome. We retrospectively reviewed patients aged ≤ 18 years who underwent allogeneic HSCT between April 2005 and April 2020. The outcomes of interest included the incidence of GVHD, overall survival (OS), and IR. IR was analyzed through thymic magnetic resonance imaging (MRI) and by quantifying T CD4+ and recent thymic emigrants (RTEs). The ATG-exposed group was split into a low ATG/lymphocyte ratio subgroup (ratio 〈 0.01) and a high ATG/lymphocyte ratio subgroup (ratio 〉 0.01). The low ratio subgroup had a higher incidence of GVHD (29 [59%] vs. 7 [16.6%] ) but a better IR in both laboratory and MRI imaging assessments (p 〈 0.0001). The median thymic volume in the low ratio subgroup was significantly higher (14.7 cm3 vs. 4.5 cm3, p 〈 0.001). This was associated with a better OS and lower transplant-related mortality (TRM) (80.4% vs. 58.0%, p = 0.031) and (13.1% vs. 33.0%, p = 0.035). An individualized approach to ATG dosing allows for the obtainment of rapid thymic reconstitution and the best transplant-related outcomes.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 3
    In: Pharmaceuticals, MDPI AG, Vol. 15, No. 3 ( 2022-03-19), p. 374-
    Abstract: Janus kinases (JAK) are a family of tyrosine kinases (JAK1, JAK2, JAK3, and TYK2) that transduce cytokine-mediated signals through the JAK–STAT metabolic pathway. These kinases act by regulating the transcription of specific genes capable of inducing biological responses in several immune cell subsets. Inhibition of Janus kinases interferes with the JAK–STAT signaling pathway. Besides being used in the treatment of cancer and inflammatory diseases, in recent years, they have also been used to treat inflammatory conditions, such as graft-versus-host disease (GVHD) and cytokine release syndrome as complications of allogeneic hematopoietic stem cell transplantation and cell therapy. Recently, the FDA approved the use of ruxolitinib, a JAK1/2 inhibitor, in the treatment of acute steroid-refractory GVHD (SR-aGVHD), highlighting the role of JAK inhibition in this immune deregulation. Ruxolitinib was initially used to treat myelofibrosis and true polycythemia in a high-dose treatment and caused hematological toxicity. Since a lower dosage often could not be effective, the use of ruxolitinib was suspended. Subsequently, ruxolitinib was evaluated in adult patients with SR-aGVHD and was found to achieve a rapid and effective response. In addition, its early low-dose use in pediatric patients affected by GVHD has proved effective, safe, and reasonably preventive. The review aims to describe the potential properties of ruxolitinib to identify new therapeutic strategies.
    Type of Medium: Online Resource
    ISSN: 1424-8247
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2193542-7
    SSG: 15,3
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  • 4
    In: Antibiotics, MDPI AG, Vol. 12, No. 4 ( 2023-04-06), p. 712-
    Abstract: Background: Antimicrobial and diagnostic stewardship (AS/DS) principles are crucial for the management of multidrug-resistant organisms (MDROs) infections. We evaluated the impact of a pro-active Infectious Disease (ID) consultation on the mortality risk of patients during an MDROs outbreak in a COVID-19 hospital. Methods: A quasi-experimental study was performed in a dedicated COVID-19 hospital, including patients with suspected/confirmed infection and/or colonization by MDROs, which were managed as follows: (i) according to the standard of care during the pre-phase and (ii) in collaboration with a dedicated ID team performing a pro-active bedside evaluation every 48–72 h in the post-phase. Results: Overall, 112 patients were included (pre-phase = 89 and post-phase = 45). The AS interventions included the following: therapy optimization (33%), de-escalation to narrow the spectrum (24%) or to lessen toxic drugs (20%), and discontinuation of antimicrobials (64%). DS included the request of additional microbiologic tests (82%) and instrumental exams (16%). With the Cox model, after adjusting for age, sex, COVID-19 severity, infection source, etiological agents, and post-phase attendance, only age predicted an increased risk of mortality, while attendance in the post-phase resulted in a decreased risk of mortality. Conclusions: Implementation of AS and DS intervention through a pro-active ID consultation may reduce the risk of 28-day mortality of COVID-19 patients with MDROs infections.
    Type of Medium: Online Resource
    ISSN: 2079-6382
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2681345-2
    SSG: 15,3
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  • 5
    In: Energies, MDPI AG, Vol. 14, No. 24 ( 2021-12-15), p. 8480-
    Abstract: In this work, a strategy for scheduling a battery energy storage system (BESS) in a renewable energy community (REC) is proposed. RECs have been defined at EU level by the 2018/2001 Directive; some Member States transposition into national legislation defined RECs as virtual microgrids since they still use the existing low voltage local feeder and share the same low-medium voltage transformer. This work analyzes a REC which assets include PV generators, BESS and non-controllable loads, operating under the Italian legislative framework. A methodology is defined to optimize REC economic revenues and minimize the operation costs during the year. The proposed BESS control strategy is composed by three different modules: (i) a machine learning-based forecast algorithm that provides a 1-day-ahead projection for microgrid loads and PV generation, using historical dataset and weather forecasts; (ii) a mixed integer linear programming (MILP) algorithm that optimizes the BESS scheduling for minimal REC operating costs, taking into account electricity price, variable feed-in tariffs for PV generators, BESS costs and maximization of the self-consumption; (iii) a decision tree algorithm that works at the intra-hour level, with 1 min timestep and with real load and PV generation measurements adjusting the BESS scheduling in real time. Validation of the proposed strategy is performed on data acquired from a real small-scale REC set up with an Italian energy provider. A 10% average revenue increase could be obtained for the prosumer alone when compared to the non-optimized BESS usage scenario; such revenue increase is obtained by reducing the BESS usage by around 30% when compared to the unmanaged baseline scenario.
    Type of Medium: Online Resource
    ISSN: 1996-1073
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2437446-5
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  • 6
    In: Applied Sciences, MDPI AG, Vol. 10, No. 19 ( 2020-09-27), p. 6755-
    Abstract: The use of electronic loads has improved many aspects of everyday life, permitting more efficient, precise and automated process. As a drawback, the nonlinear behavior of these systems entails the injection of electrical disturbances on the power grid that can cause distortion of voltage and current. In order to adopt countermeasures, it is important to detect and classify these disturbances. To do this, several Machine Learning Algorithms are currently exploited. Among them, for the present work, the Long Short Term Memory (LSTM), the Convolutional Neural Networks (CNN), the Convolutional Neural Networks Long Short Term Memory (CNN-LSTM) and the CNN-LSTM with adjusted hyperparameters are compared. As a preliminary stage of the research, the voltage and current time signals are simulated using MATLAB Simulink. Thanks to the simulation results, it is possible to acquire a current and voltage dataset with which the identification algorithms are trained, validated and tested. These datasets include simulations of several disturbances such as Sag, Swell, Harmonics, Transient, Notch and Interruption. Data Augmentation techniques are used in order to increase the variability of the training and validation dataset in order to obtain a generalized result. After that, the networks are fed with an experimental dataset of voltage and current field measurements containing the disturbances mentioned above. The networks have been compared, resulting in a 79.14% correct classification rate with the LSTM network versus a 84.58% for the CNN, 84.76% for the CNN-LSTM and a 83.66% for the CNN-LSTM with adjusted hyperparameters. All of these networks are tested using real measurements.
    Type of Medium: Online Resource
    ISSN: 2076-3417
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2704225-X
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