Robust model predictive control for dynamics compensation in real-time hybrid simulation

Hybrid simulation is an efficient method to obtain the response of an emulated system subjected to dynamic excitation by combining loading-rate-sensitive numerical and physical substructures. In such simulations, the interfaces between physical and numerical substructures are usually implemented using transfer systems, i.e., an arrangement of actuators. To guarantee high fidelity of the simulation outcome, conducting hybrid simulation in hard real-time is required. Albeit attractive, real-time hybrid simulation comes with numerous challenges, such as the inherent dynamics of the transfer system used, along with communication interrupts between numerical and physical substructures, that introduce time delays to the overall hybrid model altering the dynamic response of the system under consideration. Hence, implementation of adequate control techniques to compensate for such delays is necessary. In this study, a novel control strategy is proposed for time delay compensation of actuator dynamics in hard real-time hybrid simulation applications. The method is based on designing a transfer system controller consisting of a robust model predictive controller along with a polynomial extrapolation algorithm and a Kalman filter. This paper presents a proposed tracking controller first, followed by two virtual real-time hybrid simulation parametric case studies, which serve to validate the performance and robustness of the novel control strategy. Real-time hybrid simulation using the proposed control scheme is demonstrated to be effective for structural performance assessment

Real world data on the prognostic significance of monocytopenia in myelodysplastic syndrome

Monocytopenia is a common finding in patients with myelodysplastic syndrome (MDS), but although monocytes may exhibit prognostic significance in MDS due to their role in innate immunity, they have not been incorporated in any prognostic scoring system for MDS. In this study, we analyzed national registry data from 1719 adults with MDS. Monocytopenia was present in 29.5% of the patients and was correlated with the presence of excess blasts and higher revised international prognostic scoring system categories. Univariate analysis showed that monocytopenia was prognostic of a lower overall survival [(OS), 32.0 versus 65.0 months, p < 0.001], while it retained its prognostic significance in a multivariate model comprising anemia, neutropenia and thrombocytopenia [hazard ratio (HR) for OS, 1.320, p < 0.001]. Moreover, it was prognostic of a lower leukemia free survival (LFS) both in univariate analysis and in a multivariate model comprising cytopenias, bone marrow blasts, and cytogenetic risk (HR for LFS 1.27, p = 0.031). The findings regarding OS and LFR were exclusive or more pronounced in lower risk patients, respectively. Moreover, monocytopenia could divide the low and intermediate risk groups of IPSS-R in prognostically distinct subgroups. Our results redefine the prognostic role of monocytes in MDS and set the basis for further studies to validate our results and expand our knowledge on the prognostic significance of monocytopenia in MDS. © 2022, The Author(s)

Estimated glomerular filtration rate independently predicts outcome of azacitidine therapy in higher-risk Myelodysplastic syndromes. Results from 536 patients of the Hellenic National Registry of Myelodysplastic and Hypoplastic syndromes

Higher-risk Myelodysplastic syndromes (MDS) patients undergoing treatment with 5-azacytidine (AZA) are typically elderly with several comorbidities. However, the effect of comorbidities on the effectiveness and safety of AZA in real-world settings remains unclear. We analyzed data from 536 AZA-treated patients with higher-risk MDS, Myelodysplastic/Myeloproliferative neoplasms and low blast count Acute Myeloid Leukemia enrolled to the Hellenic National Registry of Myelodysplastic and Hypoplastic Syndromes. Multivariate analysis adjusted also for the International Prognostic Scoring System (IPSS), its revised version (IPSS-R) and the French Prognostic Scoring System (FPSS), demonstrated independent associations of overall and leukemia-free survival with estimated glomerular filtration rate (eGFR) &amp;lt;45 mL min−1/1.73 m2 (P =.039, P =.023, respectively), ECOG performance status &amp;lt;2 (P =.015, P =.006), and presence of peripheral blood blasts (P =.008, P =.034), while secondary MDS also correlated with significantly shorter leukemia-free survival (P =.039). Addition of eGFR &amp;lt;45 mL min−1/1.73 m2, in IPSS-R and FPSS increased the predictive power of both models. Only FPSS ≤2 and eGFR &amp;lt;45 mL min−1/1.73 m2 predicted worse response to AZA in multivariate analysis, whereas eGFR &amp;lt;45 mL min−1/1.73 m2 correlated significantly with death from hemorrhage (P =.003) and cardiovascular complications (P =.006). In conclusion, in the second largest real-world series of AZA-treated MDS patients, we show that an eGFR &amp;lt;45 mL min−1/1.73 m2 is an independent predictor of worse response and survival. This higher cut-off, instead of the commonly used serum creatinine &amp;gt;2 mg/dL, can be utilized as a more precise indicator of renal comorbidity during AZA therapy. Incorporation of eGFR in the prognostic assessment of AZA-treated MDS patients may prove useful not only in routine practice, but also for the appropriate patient stratification in clinical trials with AZA combinations. © 2020 John Wiley &amp; Sons Lt

Characteristics of Long-Term Survival in Patients With Myelodysplastic Syndrome Treated With 5-Azacyditine: Results From the Hellenic 5-Azacytidine Registry

Background: Hypomethylating agents have altered the prognosis of myelodysplastic syndrome (MDS) so that long-term survival is now a feasible treatment goal. Patients and Methods: We analyzed data from patients with MDS treated with 5-azacytidine recorded in the Hellenic 5-azacytidine registry. We divided patients, on the basis of their survival after 5-azacytidine initiation (OST), in groups of long-term survivors (Q3 and P90 group with OST above the third quartile and the 90th percentile of the whole group, respectively) and short-term survivors comprising the remaining patients, and compared the characteristics between the groups. The study included 626 patients, 157 in the Q3 group and 63 in the P90 group. Results: Categorization per the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R), and World Health Organization–based prognostic scoring system (WPSS) was found to predict long-term survival, while multivariate analysis revealed that response to 5-azacytidine was the strongest predictor of long-term survival. Nevertheless, patients with hematologic improvement (HI) and stable disease (SD) were equally distributed in the groups of short- and long-term survival. Conclusion: SD should not be considered a poor treatment response and should not be grouped with failure, while HI offers similar prognosis to SD and thus should not be grouped with complete and partial remission. Patients with SD should continue treatment with 5-azacytidine. The prognosis of myelodysplastic syndrome (MDS) has changed since the introduction of hypomethylating agents that offer the potential for long-term survival. We studied the characteristics of long-term survival in a cohort of 626 patients with MDS treated with 5-azacytidine; response was found to be the single most important predictive factor of long-term survival, while stable disease (SD) and hematologic improvement were equally distributed in the groups with long- and short-term survival. Achieving SD has prognostic significance, and SD should not be grouped with treatment failure. © 2019 Elsevier Inc

Characteristics of Long-Term Survival in Patients With Myelodysplastic Syndrome Treated With 5-Azacyditine: Results From the Hellenic 5-Azacytidine Registry

Background: Hypomethylating agents have altered the prognosis of myelodysplastic syndrome (MDS) so that long-term survival is now a feasible treatment goal. Patients and Methods: We analyzed data from patients with MDS treated with 5-azacytidine recorded in the Hellenic 5-azacytidine registry. We divided patients, on the basis of their survival after 5-azacytidine initiation (OST), in groups of long-term survivors (Q3 and P90 group with OST above the third quartile and the 90th percentile of the whole group, respectively) and short-term survivors comprising the remaining patients, and compared the characteristics between the groups. The study included 626 patients, 157 in the Q3 group and 63 in the P90 group. Results: Categorization per the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R), and World Health Organization–based prognostic scoring system (WPSS) was found to predict long-term survival, while multivariate analysis revealed that response to 5-azacytidine was the strongest predictor of long-term survival. Nevertheless, patients with hematologic improvement (HI) and stable disease (SD) were equally distributed in the groups of short- and long-term survival. Conclusion: SD should not be considered a poor treatment response and should not be grouped with failure, while HI offers similar prognosis to SD and thus should not be grouped with complete and partial remission. Patients with SD should continue treatment with 5-azacytidine. The prognosis of myelodysplastic syndrome (MDS) has changed since the introduction of hypomethylating agents that offer the potential for long-term survival. We studied the characteristics of long-term survival in a cohort of 626 patients with MDS treated with 5-azacytidine; response was found to be the single most important predictive factor of long-term survival, while stable disease (SD) and hematologic improvement were equally distributed in the groups with long- and short-term survival. Achieving SD has prognostic significance, and SD should not be grouped with treatment failure. © 2019 Elsevier Inc

The effect of 5-azacytidine treatment delays and dose reductions on the prognosis of patients with myelodysplastic syndrome: how to optimize treatment results and outcomes

The regimen of 5-azacytidine for patients with myelodysplastic syndrome (MDS) has remained unchanged since its first approval. Although several modifications have since been made and delays and dose reductions are common especially during the first treatment cycles, there are minimal data on the prognostic effect of these modifications. In this study, based on data from 897 patients with MDS treated with 5-azacytidine recorded in a national registry, the effect of treatment delays and dose reductions on response, transformation to acute myeloid leukaemia, and survival (after 5-azacytidine initiation, OST) were analysed. Delays during the first two cycles were noted in 150 patients (16·7%) and were found to adversely affect OST independently of the International Prognostic Scoring System score [hazard ratio (HR), 1·368; P = 0·033] or pre-existing neutropenia (HR, 1·42; P = 0·015). In patients achieving a response, delays before response achievement were correlated with its type (complete remission, 2·8 days/cycle; partial remission, 3·3 days/cycle; haematologic improvement, 5·6 days/cycle; P = 0·041), while delays after response achievement did not have any effect on retention of response or survival. Dose reductions were found to have no prognostic impact. Based on our results, treatment delays especially during the first cycles should be avoided, even in neutropenic patients. This strict strategy may be loosened after achieving a favourable response. © 2020 British Society for Haematology and John Wiley & Sons Lt

Chronic myelomonocytic leukemia treated with 5-azacytidine–results from the Hellenic 5-Azacytidine Registry: proposal of a new risk stratification system

Hypomethylating agents are widely used in chronic myelomonocytic leukemia (CMML). We analyzed the characteristics of 88 patients with CMML homogeneously treated with 5-azacytidine (Hellenic 5-Azacytidine Registry). The overall response rate was 48.9% and the median overall survival (OS) 29.7 months. Out of the seven most widely used prognostic scoring systems for CMML, the Dusseldorf score (DUSS) showed the best prognostic capability (HR, 2.27; p &amp;lt;.001). Forty-one (48.8%) patients progressed to acute myeloid leukemia (AML) after a median time of 15.2 months following treatment initiation. High serum ferritin levels at diagnosis were independently correlated with low OS (HR, 2.84; p =.022), as were circulating blasts (HR, 3.47; p =.014), while a platelet count &amp;lt;100 × 109/L was marginally predictive of lower OS (HR, 1.45; p =.06). We selected these three factors to create a new risk stratification system for CMML with three risk groups. Finally, we highlighted for the first time the prognostic significance of serum ferritin levels in CMML. © 2018, © 2018 Informa UK Limited, trading as Taylor &amp; Francis Group