80 research outputs found

    An evidence-based and risk-adapted GSF versus GSF plus plerixafor mobilization strategy to obtain a sufficient CD34+ cell yield in the harvest for autologous stem cell transplants

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    Background: Plerixafor is a bicyclam molecule with the ability to reversibly bind to receptor CXCR-4 thus leading to an increased release of stem cells (SC) into the circulation. This study aims to evaluate the efficacy of G-CSF plus plerixafor versus G-CSF alone mobilizing regimens on the basis of CD34+ cell yield and engraftment kinetics following hematopoietic SC transplants. Methods: The study incorporated 173 patients with plasma cell neoplasms (PCN), Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL), undergoing mobilization and following autologous SC-transplant. For patients with mobilization failure and those predicted to be at risk of harvesting inadequate CD34+ yields (poor-responders), plerixafor was administered. Data was collected and compared in relation to the harvesting protocols used, cell quantification, cell-engraftment potential and overall clinical outcome. Results: A total of 101 patients received plerixafor (58.4Ā %) and the median CD34+increase was 312Ā %. Chemotherapy-mobilized PCN-patients required less plerixafor administration (pĀ =Ā 0.01), no difference was observed in lymphoma groups (pĀ =Ā 0.46). The median CD34+cell yield was 7.8Ā Ć—Ā 106/kg bm. Patients requiring plerixafor achieved lower, but still comparable cell yields. Total cell dose infused was in correlation with engraftment kinetics. Patients requiring plerixafor had delayed platelet engraftment (pĀ =Ā 0.029). Conclusions: Adequately selected plerixafor administration reduces ''mobilization-related-failure'' rate and assure a high-level cell dose for SC transplants, with superior ''therapeutic-potential'' and safety profile. The mobilization strategy that incorporates ''just-in-time'' plerixafor administration, also leads to a reduction of hospitalization days and healthcare resource utilization. For definitive conclusions, further controlled/larger clinical trials concerning correlation of CD34+ cell count/yield, with hematopoietic reconstitution are required

    Worst Case Uncertainty Construction via Multifrequency Gain Maximization With Application to Flutter Control

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    In the analysis of uncertain systems, we often search for a worst case perturbation that drives the Hāˆž gain of the system to the maximum over the set of allowable uncertainties. Employing the classical technique, an uncertainty sample is obtained, which, indeed, maximizes the gain but only at the single frequency where that maximum occurs. In contrast, this article considers a method to calculate a worst case perturbation that maximizes the gain of a system with mixed uncertainty at multiple frequencies simultaneously. This approach involves a nonlinear optimization that selects the worst case value of the uncertain parameters and the application of the boundary Nevanlinna-Pick interpolation to calculate the dynamic uncertainty sample. Such a perturbation can be used to augment Monte Carlo simulations of uncertain systems, especially if the system has multiple resonance frequencies. The worst case analysis of a flutter control system designed for a small flexible aircraft is provided to demonstrate the applicability of the proposed method

    Diagnostic Performance of On-Site Computed Tomography Derived Fractional Flow Reserve on Non-Culprit Coronary Lesions in Patients with Acute Coronary Syndrome

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    The role of coronary computed tomography angiography (CCTA) derived fractional flow reserve (CT-FFR) in the assessment of non-culprit lesions (NCL) in patients with acute coronary syndrome (ACS) is debated. In this prospective clinical study, a total of 68 ACS patients with 89 moderate (30–70% diameter stenosis) NCLs were enrolled to evaluate the diagnostic accuracy of on-site CT-FFR compared to invasive fractional flow reserve (FFRi) and dobutamine stress echocardiography (DSE) as reference standards. CT-FFR and FFRi values ≤0.80, as well as new or worsening wall motion abnormality in ≥2 contiguous segments on the supplying area of an NCL on DSE, were considered positive for ischemia. Sensitivity, specificity, positive, and negative predictive value of CT-FFR relative to FFRi and DSE were 51%, 89%, 75%, and 74% and 37%, 77%, 42%, and 74%, respectively. CT-FFR value (β = 0.334, p < 0.001) and CT-FFR drop from proximal to distal measuring point [(CT-FFR drop), β = −0.289, p = 0.002)] were independent predictors of FFRi value in multivariate linear regression analysis. Based on comparing their receiver operating characteristics area under the curve (AUC) values, CT-FFR value and CT-FFR drop provided better discriminatory power than CCTA-based minimal lumen diameter stenosis to distinguish between an NCL with positive and negative FFRi [0.77 (95% Confidence Intervals, CI: 0.67–0.86) and 0.77 (CI: 0.67–0.86) vs. 0.63 (CI: 0.52–0.73), p = 0.029 and p = 0.043, respectively]. Neither CT-FFR value nor CT-FFR drop was predictive of regional wall motion score index at peak stress (β = −0.440, p = 0.441 and β = 0.403, p = 0.494) or was able to confirm ischemia on the territory of an NCL revealed by DSE (AUC = 0.54, CI: 0.43–0.64 and AUC = 0.55, CI: 0.44–0.65, respectively). In conclusion, on-site CT-FFR is superior to conventional CCTA-based anatomical analysis in the assessment of moderate NCLs; however, its diagnostic capacity is not sufficient to make it a gatekeeper to invasive functional evaluation. Moreover, based on its comparison with DSE, CT-FFR might not yield any information on the microvascular dysfunction in the territory of an NCL

    Systemic inflammatory response syndrome in dogs naturally infected with Babesia canis: Association with the parasite load and host factors

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    The common signs of canine babesiosis caused by an infection with Babesia canis are fever, anorexia, lethargy, pulse alterations, anemia, and occasionally mild icterus. Dogs with these clinical signs can be divided into two groups: those with acute-phase reaction and those with systemic inflammatory response syndrome (SIRS). Factors associated with the occurrence of SIRS in canine babesiosis have not been thoroughly researched. This article outlines a cross-sectional study of 54 client-owned dogs with an acute B. canis infection, and evaluates the differences in age, gender, laboratory findings, parasite load, and seroreactivity against B. canis between the SIRS and the SIRS-free dogs. We have analyzed a complete blood count, serum biochemistry, serum amyloid A, ceruloplasmin, paraoxonase-1, serology, and PCR testing using standard methodologies. The frequency of SIRS among the investigated dogs reached 0.59. Male dogs and those seronegative against B. canis, were more frequent in the SIRS group, whilst age and parasite load could not be associated with the presence of SIRS. Dogs with SIRS had a lower count of total leukocytes, neutrophils, lymphocytes, and monocytes, and a lower concentration of iron and bilirubin compared with SIRS-free dogs. No significant differences in the concentration of acute-phase proteins have been noticed to exist between the groups of dogs. Further, the seronegative dogs had a lower count of lymphocytes and monocytes and a higher parasite load than the seroreactive dogs. Multivariate logistic regression analysis has identified leukopenia (<6 Ɨ 109/L) and monocytopenia (<0.2 Ɨ 109/L) as independent associates of SIRS in the investigated dogs, thus implying that these routine tests could be used as reliable markers for SIRS

    Predictors of Mortality in Critically Ill COVID-19 Patients Demanding High Oxygen Flow: A Thin Line between Inflammation, Cytokine Storm, and Coagulopathy

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    Introduction. Mortality among critically ill COVID-19 patients remains relatively high despite different potential therapeutic modalities being introduced recently. The treatment of critically ill patients is a challenging task, without identified credible predictors of mortality. Methods. We performed an analysis of 160 consecutive patients with confirmed COVID-19 infection admitted to the Respiratory Intensive Care Unit between June 23, 2020, and October 2, 2020, in University Hospital Center Bezanijska kosa, Belgrade, Serbia. Patients on invasive, noninvasive ventilation and high flow oxygen therapy with moderate to severe ARDS, according to the Berlin definition of ARDS, were selected for the study. Demographic data, past medical history, laboratory values, and CT severity score were analyzed to identify predictors of mortality. Univariate and multivariate logistic regression models were used to assess potential predictors of mortality in critically ill COVID-19 patients. Results. The mean patient age was 65.6 years (range, 29ā€“92 years), predominantly men, 68.8%. 107 (66.9%) patients were on invasive mechanical ventilation, 31 (19.3%) on noninvasive, and 22 (13.8%) on high flow oxygen therapy machine. The median total number of ICU days was 10 (25th to 75th percentile: 6ā€“18), while the median total number of hospital stay was 18 (25th to 75th percentile: 12ā€“28). The mortality rate was 60% (96/160). Univariate logistic regression analysis confirmed the significance of age, CRP, and lymphocytes at admission to hospital, serum albumin, D-dimer, and IL-6 at admission to ICU, and CT score. Serum albumin, D-dimer, and IL-6 at admission to ICU were independently associated with mortality in the final multivariate analysis. Conclusion. In the present study of 160 consecutive critically ill COVID-19 patients with moderate to severe ARDS, IL-6, serum albumin, and D-dimer at admission to ICU, accompanied by chest CT severity score, were marked as independent predictors of mortality

    Influence of applied CD34+ cell dose on the survival of Hodgkin's lymphoma and multiple myeloma patients following autologous stem cell transplants

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    Background/Aim. Autologous stem cell transplants (ASCTs) improve the rate of overall survival (OS) in patients with hematological malignancies such as multiple myeloma (MM) after induction chemotherapy, aggressive non-Hodgkin's lymphomas (NHL), and relapsed, chemotherapy-sensitive Hodgkin's lymphoma (HL). The study aim was to evaluate influence of applied CD34+ cell quantity on clinical outcome, as well as early post-transplant and overall survival (OS) of HL and MM patients following ASCT. Methods. This study included a total of 210 patients (90 HL/120 MM) who underwent ASCT. Stem cell (SC) mobilization was accomplished by granulocyte-colony stimulating factor (G-CSF) 10ā€“16 Ī¼g/kg body mass (bm) following chemotherapy. For proven poor mobilizers, mobilization with G-CSF (16 Ī¼g/kgbm) and Plerixafor (24 or 48 mg) was performed. To our best knowledge, it was the first usage of the Plerixafor in our country in the ASCT-setting. Harvesting was initiated merely at "cut-off-value" of CD34+ cells ā‰„ 20 Ɨ 106/L in peripheral blood with "target-dose" of CD34+ cells ā‰„ 5 Ɨ 106/kgbm in harvest. The CD34+ cell count and viability was determined using flow cytometry. Results. The majority of HL patients (76.7%) were infused with > 5.0 Ɨ 106/kgbm CD34+ cells, while 68.3% of MM patients were treated by approximately 4.0ā€“5.4 Ɨ 106/kgbm CD34+ dose, respectively. Beneficial response (complete/partial remission) was achieved in 83.3% (HL) and 94.2% (MM) patients. Among parameters that influenced survival of HL patients with positive response to the therapy, multivariate analysis (pre-ASCT performance status, CD34+ cell quantity applied, rapid hematopoietic, i.e. lymphocyte and platelet recovery) indicated that higher CD34+ cell dose used, along with pre-ASCT performance status correlated with superior event-free survival (EFS) and OS following ASCT. In MM patients, multivariate analysis (renal impairment, infused CD34+ cell quantity, early platelet recovery) indicated that the number of CD34+ cells infused was the most important parameter that influenced both EFS and OS after ASCT. Conclusion. Data obtained in this study undoubtedly confirmed that CD34+ cell dose applied is an independent factor that may contribute to superior clinical outcome and OS of HL and MM patients following ASCT

    Aerodynamic and LPV Modeling of a Distributed Propulsion Morphing Wing Aircraft

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    Hybrid-electric, unconventional aircraft solutions can possibly be the solutions for the ambitious emission reduction targets set by regulators, based on societyā€™s demands. One such disruptive solution is a morphing wing cargo UAV, with distributed propulsion. This paper investigates the aerodynamics, flight dynamics and control of a scaled down technology demon- strator UAV, built to validate the feasibility of the morphing wing concept. Several types of analyses are run to gain knowledge on the performance, stability and control properties of the aircraft. The flight mechanical effects of the distributed propulsion system are taken into account based on the integral momentum theorem. The increased flow speed behind propellers increases the local lift forces. Therefore, the distributed propulsion can be used to control the roll, pitch and yaw motion of the morphing wing aircraft. The nonlinear 6 degrees of freedom, distributed propulsion aircraft model is constructed utilizing the stability and control derivatives obtained from the aerodynamic analysis. Grid and Tensor Product (TP) type linear parameter-varying (LPV) models of the morphing wing aircraft are generated via Jacobian linearization and TP model transformation. The LPV models capture the parameter varying dynamics arising from the airspeed, morphing wing and payload weight variations. Gain scheduled lateral and longitudinal baseline controllers are synthesized using the grid-based LPV model of the aircraft

    Rapid Cytoreduction by Plateletapheresis in the Treatment of Thrombocythemia

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    The objective of this chapter is to provide a systematic overview of current knowledge regarding therapeutic apheresisā€”primarily therapeutic plateletapheresis (TP)ā€”and to summarize evidence-based practical approaches related to cytapheresis treatment of ā€œhyperthrombocytosisā€ or ā€œextreme thrombocytosisā€ (ETC). Our results of platelet (Plt) quantitative/qualitative analyses and evaluation of efficacy of apheresis systems/devicesā€”on the basis of Plt removal and in vivo Plt depletionā€”will be presented. Our preclinical researches confirmed that in Plt concentrates, the initial ratio of discoid shapes was 70%, spherical 20%, and less valuable (dendritic/balloonized) shapes 10%ā€”with morphological score of platelets (MSP = 300ā€“400). After storage, the ratio of discoid and spherical shapes was decreased, while the less valuable ones progressively increased (MSP = 200). Electron microscopy has shown discoid shapes with typical ultrastructural properties. Spherical shapes with reduced electron density and peripheral location of granules/organelles were detected. Also, dendritic shapes with cytoskeletal ā€œrearrangement,ā€ membrane system integrity damages, and pseudopodia formations were documented. Our clinical study demonstrated that TP was useful in ETC treatment and should help prevention of ā€œthrombo-hemorrhagicā€ eventsā€”until chemotherapy, antiplatelet drugs, and other medication take effect. During TP treatment, Plt count and morphology/ultrastructure were examined. Plt functions by multiplate analyzer were evaluated. We concluded that intensive TP was an effective, safe, and rapid cytoreductive treatment for ET
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