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1
Benaida, Fouad, and Noureddine Benouzza. "Diagnosis of Broken Rotor Bars in Six-Phases Squirrel Cage Induction Motor." International Review of Electrical Engineering (IREE) 17, no. 5 (October 31, 2022): 489. http://dx.doi.org/10.15866/iree.v17i5.21723.
2
Iduh, Samuel E., and Silas E. Omugbe. "The design and practical implementation of a six-phase induction motor." Journal of Advances in Science and Engineering 3, no. 1 (August 1, 2020): 1–77. http://dx.doi.org/10.37121/jase.v3i1.95.
Анотація:
This thesis presents a re-designed conventional three phase 5-hp squirrel cage, 4-pole, 48 slots induction motor to a six-phase induction motor (SPIM). It also presents the in-depth of a single layer winding of a three-phase motor that was re-design to the six-phase split winding layout which was practically explained to the understanding of both the engineers and the technicians who normally find it difficult with windings of electrical machines. The optimized re-designed SPIM is presented in the MATLAB/Simulink environment to perform a comparative assessment of the different phase loss scenarios of the six-phase configuration with respect to the six-phase healthy case and its conventional three-phase induction motor. The result shows a comparative benefit of the six-phase induction motor over the three-phase induction motor; in such that in the near future because of its effective way to provide a higher reliability and sustainability under the loss of phase/phases condition it will be practically applied in the power driven devices/machines like in the area of Electric Vehicles, etc.
3
Ehara, Masahiko, Mamoru Iwami, Yoshio Ichinose, Toshiya Hirayama, M. John Albert, R. Bradley Sack, and Shoichi Shimodori. "Induction of Fimbriated Vibrio cholerae O139." Clinical Diagnostic Laboratory Immunology 5, no. 1 (January 1, 1998): 65–69. http://dx.doi.org/10.1128/cdli.5.1.65-69.1998.
Анотація:
ABSTRACT Several fimbriated phases of Vibrio cholerae O139 strains were selectively induced and compared immunologically and biochemically with those of V. cholerae O1. Fimbrial antigens were detected on the surfaces of vibrio cells colonizing the epithelial cells of a rabbit small intestine. Convalescent-phase sera from six individuals infected with V. cholerae O139 revealed the development of antibody against the fimbrillin. These findings suggest that the fimbriae of V. cholerae O1 and O139 are expressed in vivo during infection and that consideration must be given to the use of fimbrial antigens as components of vaccines against cholera.
4
Betin, Franck, and Gérard-André Capolino. "Shaft Positioning for Six-Phase Induction Machines With Open Phases Using Variable Structure Control." IEEE Transactions on Industrial Electronics 59, no. 6 (June 2012): 2612–20. http://dx.doi.org/10.1109/tie.2011.2138113.
5
Carvalho Souza, Francisco Elvis, Werbet Silva, Andrés Ortiz Salazar, José Paiva, Diego Moura, and Elmer Rolando Llanos Villarreal. "A Novel Driving Scheme for Three-Phase Bearingless Induction Machine with Split Winding." Energies 14, no. 16 (August 12, 2021): 4930. http://dx.doi.org/10.3390/en14164930.
Анотація:
In order to reduce the costs of implementing the radial position control system of a three-phase bearingless machine with split winding, this article proposes a driving method that uses only two phases of the system instead of the three-phase traditional one. It reduces from six to four the number of inverter legs, drivers, sensors, and current controllers necessary to drive and control the system. To justify the proposal, this new power and control configuration was applied to a 250 W machine controlled by a digital signal processor (DSP). The results obtained demonstrated that it is possible to carry out the radial position control through two phases, without loss of performance in relation to the conventional three-phase drive and control system.
6
Fnaiech, M. A., F. Betin, G. A. Capolino, and F. Fnaiech. "Fuzzy Logic and Sliding-Mode Controls Applied to Six-Phase Induction Machine With Open Phases." IEEE Transactions on Industrial Electronics 57, no. 1 (January 2010): 354–64. http://dx.doi.org/10.1109/tie.2009.2034285.
7
Gör, Halil. "Feasibility of Six Metaheuristic Solutions for Estimating Induction Motor Reactance." Mathematics 12, no. 3 (February 2, 2024): 483. http://dx.doi.org/10.3390/math12030483.
Анотація:
Industry is the primary application for induction machines. As such, it is essential to calculate the induction devices’ electrical properties accurately. With DC testing, no-load rotor tests, and locked rotor tests, one may empirically evaluate the electrical variables of induction motors. These tests are expensive and difficult to conduct, however. The information supplied by machine makers can also be used to accurately approximate the equivalent variables of the circuits in induction machines. This article has successfully predicted motor reactance (Xm) for both double- and single-cage models using artificial neural networks (ANN). Although ANNs have been investigated in the literature, the ANN structures were trained to use unmemorized training. Besides ANN, six other approaches have been suggested to address this issue: heap-based optimization (HBO), leagues championship algorithm (LCA), multi-verse optimization (MVO), osprey optimization algorithm (OOA), cuckoo optimization algorithm (COA), and sooty tern optimization algorithm (STOA). The efficaciousness of the suggested approaches was compared with each another. Regarding the obtained outcomes, the suggested MVO- multi-layer perceptron (MLP) technique performed better than the other five methods regarding reactance prediction, with R2 of 0.99598 and 0.9962, and RMSE of 20.31492 and 20.80626 in the testing and training phases, respectively. For the projected model, the suggested ANNs have produced great results. The novelty lies in the mentioned methods’ ability to tackle the complexities and challenges associated with induction motor reactance optimization, providing innovative approaches to finding optimal or near-optimal solutions. As researchers continue to explore and refine these techniques, their impact on motor design and efficiency will likely grow, driving advancements in electrical engineering.
8
Kianinezhad, R., B. Nahid-Mobarakeh, L. Baghli, F. Betin, and G. A. Capolino. "Modeling and Control of Six-Phase Symmetrical Induction Machine Under Fault Condition Due to Open Phases." IEEE Transactions on Industrial Electronics 55, no. 5 (May 2008): 1966–77. http://dx.doi.org/10.1109/tie.2008.918479.
9
Murillo, Carla, Ann B. Weil, George E. Moore, Matthias Kreuzer, and Jeff C. Ko. "Electroencephalographic and Cardiovascular Changes Associated with Propofol Constant Rate of Infusion Anesthesia in Young Healthy Dogs." Animals 13, no. 4 (February 14, 2023): 664. http://dx.doi.org/10.3390/ani13040664.
Анотація:
This study aimed to evaluate electroencephalography (EEG) and cardiovascular changes associated with propofol constant rate of infusion (CRI) anesthesia in dogs. Six dogs were each given propofol CRI to induce different anesthetic phases including induction (1 mg/kg/min for 10 min), and decremental maintenance doses of 2.4 mg per kg per min, 1.6 mg per kg per min, and 0.8 mg per kg per minute over 45 min. Processed EEG indices including patient state index (PSI), (burst) suppression ratio (SR), and spectral edge frequency (95%) were obtained continuously until the dogs recovered to sternal recumbency. The dogs were intubated and ventilated. Cardiovascular and EEG index values were compared between anesthetic phases. The PSI, SR, mean arterial blood pressure, and subjective anesthetic depth scores were highly correlated throughout anesthetic depth changes. The PSI decreased from 85.0 ± 17.3 at awake to 66.0 ± 29.0 at induction, and then sharply reduced to 19.7 ± 23.6 during maintenance and returned to 61.5 ± 19.2 at extubation. The SR increased from 15.4 ± 30.9% at induction to 70.9 ± 39.8% during maintenance and decreased to 3.4 ± 8.9% at extubation. We concluded that EEG indices can be used to aid in tracking ongoing brain state changes during propofol anesthesia in dogs.
10
Rathore, Vishal, and Krishna Bihari Yadav. "Mathematical Modeling and Numerical Analysis of SPIM Drive Using Modified SVPWM Technique." ECTI Transactions on Electrical Engineering, Electronics, and Communications 20, no. 2 (June 21, 2022): 152–62. http://dx.doi.org/10.37936/ecti-eec.2022202.246877.
Анотація:
This paper presents a modified space-vector pulse width modulation (SVPWM) technique for a five-level inverter that provides complete control over the multiple space-vector voltages of a six-phase inverter. This technique involves splitting six phases into two three-phase five-level inverters connected in parallel. A six-phase induction motor (SPIM) drive with a distributed neutral is considered as the load. This paper also presents a comparative analysis between the proposed and conventional SVPWM inverter-fed SPIM drives. To investigate the analytical developments and voltage limits, MATLAB/Simulink environment was used in this study. A prototype was developed in the laboratory for analyzing the harmonic components of the phase voltages and currents. The efficacy of the proposed technique was validated by means of comprehensive experiments, and the results discussed herein.
11
Serra, João, and Antonio J. Marques Cardoso. "A Simplified Model Predictive Control for Asymmetrical Six-Phase Induction Motors That Eliminates the Weighting Factor." Machines 10, no. 12 (December 8, 2022): 1189. http://dx.doi.org/10.3390/machines10121189.
Анотація:
The conventional model predictive control (MPC) is an attractive control scheme for the regulation of multiphase electric drives, since it easily exploits their inherent advantages. However, as the number of phases increases, the MPC’s complexity increases exponentially, posing a high computational burden. Additionally, the MPC still presents other issues related to the weighting factor design in the cost function. Accordingly, this paper proposes a low-complexity hysteresis model predictive current control (HMPCC) that can significantly reduce the computational burden, improve the motor’s performance, and completely avoid the weighting factor design. The proposed method is a hybrid control method, consisting of two distinct controls that complement one another. The hysteresis control is used to reduce the number of iterations per sampling period, thereby reducing the computational effort required to choose the voltage vector that actively produces torque/flux, and nullifying the weighting factor requirement. Finally, the MPC is used to improve the torque and current quality. The effectiveness of the proposed method is verified through experimental data, and the results emphasize the improvement of the proposed HMPCC scheme.
12
Jassim, Abdulsatar, Arkan Hussein, and Laith Abbas. "The Performance of a Three-Phase Induction Motor under and over Unbalance Voltage." Tikrit Journal of Engineering Sciences 28, no. 2 (February 10, 2021): 15–32. http://dx.doi.org/10.25130/tjes.28.2.02.
Анотація:
Voltage unbalance is an adverse global phenomenon impacting three-phase induction motor output. Three-phase source voltage may become imbalanced in a variety of respects, while a balanced system preserves stable voltage magnitude and angles in three phases, but a completely balanced state is difficult to get. Imbalanced cases may differ in multiple ranges which may practically affect the motor. So, this work is an effort to analyze the operations with appropriate propositions. The output of a three-phase induction motor working with an imbalanced supply grid, MATLAB/SIMULINK is further used for simulation purposes and programming based on the asymmetrical component approach is adopted. A new design for system rerating is being proposed. As a case study, a 10 HP three-phase induction motor was used. The findings of the study show that to determine the output of the induction motor, positive voltage series must be respected under the voltage unbalance factor (VUF) or proportion voltage unbalance index with six various voltage magnitude imbalance conditions, the copper losses of three-phase induction motors were calculated under full load conditions by simulation. So, the qualified percentage change in total copper losses for the motor operating under imbalanced and balanced voltages was determined.
13
Brown, Austin L., Rachel D. Harris, Olga A. Taylor, Melanie B. Bernhardt, Juan C. Bernini, Rodrigo A. Erana, Timothy Griffin, et al. "Abstract 3636: Ethnic disparities in methotrexate neurotoxicity during pediatric acute lymphoblastic leukemia therapy: A report from the Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium." Cancer Research 82, no. 12_Supplement (June 15, 2022): 3636. http://dx.doi.org/10.1158/1538-7445.am2022-3636.
Анотація:
Abstract Introduction: Methotrexate (MTX) is a key component of curative chemotherapy for pediatric acute lymphoblastic leukemia (ALL). However, delivery of MTX is often interrupted by dose-limiting acute neurotoxicity, which manifests as seizures, stroke-like symptoms, or altered mental status. Because incidence and risk factors for MTX neurotoxicity are poorly defined, we evaluated clinical and demographic predictors of MTX neurotoxicity using the multi-ethnic REDIAL Consortium. Methods: The REDIAL cohort includes pediatric patients diagnosed with ALL at six treatment centers in the southwestern U.S. This interim analysis evaluated 756 patients age 1-21 years diagnosed with B-ALL (2005-2018). Electronic health records were reviewed to determine race/ethnicity (Latino, non-Latino White, non-Latino Black, or Other), body mass index, sex, age, and intravenous (IV) MTX dose. Applying Ponte di Legno criteria, acute MTX neurotoxicity was defined as neurologic episodes occurring <21 days from intrathecal or IV MTX, which resulted in MTX treatment modifications. The proportion of patients who experienced MTX neurotoxicity and corresponding 95% confidence interval (CI) was calculated overall and within the induction, post-induction, and maintenance treatment phases. Multivariable logistic regression was used to estimate adjusted odds ratios (aOR) for the association between clinical factors and MTX neurotoxicity. Results: The study population was 56.6% Latino, 52.8% male, 41.4% treated with >5g/m2 IV MTX, and diagnosed at a median age of 5 years. Overall, 15.5% (95% CI: 12.9-18.3%) of patients experienced neurotoxic events (n=117), including 1.9% (n=14, 95% CI: 1.0-3.1%) during induction, 13.0% (n=98, 95% CI: 10.7-15.6%) during post-induction, and 0.7% (n=5, 95% CI: 0.2-1.5%) during maintenance therapy. Ethnic differences were not statistically significant during induction or maintenance phases. Compared to non-Latinos, post-induction neurotoxicity was significantly more frequent among Latinos (aOR = 2.87, 95% CI: 1.68-5.10), with disparities observed during consolidation, interim maintenance and delayed intensification phases. Exposure to >5g/m2 IV MTX (aOR = 2.16, 95% CI: 1.08-3.24) and older age at diagnosis (aOR = 1.16, 95% CI: 1.08-1.24) were also associated with a significantly more post-induction neurotoxicity. No factors evaluated were significantly associated with neurotoxicity during induction and maintenance therapy. Conclusions: MTX neurotoxicity disproportionally affects Latino children during ALL post-induction therapy. Additional work is warranted to identify risk factors for neurotoxicity during induction and maintenance therapy as well as the specific clinical and host biological factors responsible for post-induction ethnic differences in MTX neurotoxicity. Citation Format: Austin L. Brown, Rachel D. Harris, Olga A. Taylor, Melanie B. Bernhardt, Juan C. Bernini, Rodrigo A. Erana, Timothy Griffin, Kenneth Heym, Van T. Huynh, Kathleen Ludwig, Avner Meoded, Sandi L. Pruitt, Philip J. Lupo, Karen R. Rabin, Michael E. Scheurer. Ethnic disparities in methotrexate neurotoxicity during pediatric acute lymphoblastic leukemia therapy: A report from the Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3636.
14
Tiwari, Jitendra Kumar, Gajala Ameen, Vivek Kumar Sandilya, Ashish Kumar, and AK Singh. "Effect of IBA on root development and associated biochemical changes in single- and double-node stem-cuttings of spine gourd." Vegetable Science 49, no. 01 (June 30, 2022): 33–40. http://dx.doi.org/10.61180/vegsci.2022.v49.i1.05.
Анотація:
The present study was carried out to induce rooting in single- and double-node cuttings of Momordica dioica Roxb. variety Indira Kankoda-2 (RMDSG-3) under controlled conditions and to investigate associated biochemical changes during root development. The cuttings were treated with six different concentrations of IBA (0, 1100, 1200, 1300, 1400, 1500 mg/l) at four soaking durations (5, 10, 15 and 20 second). Among five concentrations of IBA tested, 1500 mg/l IBA + 5 seconds soaking duration gave the highest percentage of rooting, number of roots, and root length in both single and double node stem cuttings. As a result, IBA 1500 mg/l was used further in this investigation for biochemical studies. The adventitious rooting was obtained in three distinct phases i.e., induction (0–12 days), initiation (12–14 days) and expression (14–18 days). IAA-oxidase activity of cuttings treated with IBA increased slightly as compared to control, this activity was found to decrease during induction and initiation phases and increase during the expression phase. The peroxidase activity of cuttings treated IBA-1500 mg/l increased up to initiation phase and decreased during the expression phase. Polyphenoloxidase enzyme activity/mg protein/min increased in both treated (0.9-1.75) and control (0.5-0.8) cuttings during induction and initiation phase but declined slowly during the expression phase. Total phenolic content was measured in mg/gm fresh weight, and it was found to be higher (6.55 mg/g fresh weight) in IBA- 1500 mg/l treated cuttings, particularly in initiation and expression phases, and it was also positively correlated with peroxidase activity. Phenolic compounds may be used as a rooting enhancer in spine gourd, and they can play a key role in inducing adventitious rooting. IBA is found efficient in spine gourd rooting, and by utilizing this protocol i.e., double node cuttings treated with 1500 ppm IBA for 5 seconds duration, spine gourd can be commercially propagating.
15
Heath, John A., Peter G. Steinherz, Arnold Altman, Harland Sather, Suresh Jhanwar, Steven Halpern, Richard Pieters, et al. "Human Granulocyte Colony-Stimulating Factor in Children With High-Risk Acute Lymphoblastic Leukemia: A Children’s Cancer Group Study." Journal of Clinical Oncology 21, no. 8 (April 15, 2003): 1612–17. http://dx.doi.org/10.1200/jco.2003.07.129.
Анотація:
Purpose: To investigate the effect of granulocyte colony-stimulating factor (G-CSF) on hematopoietic toxicities, supportive care requirements, time to complete intensive therapy, and event-free survival (EFS) and overall survival (OS) in children with high-risk acute lymphoblastic leukemia (HR-ALL). Patients and Methods: A total of 287 children with HR-ALL were randomly assigned to intensive chemotherapy regimens (New York I [NY I] or NY II) as part of the Children’s Cancer Group (CCG)-1901 protocol. The induction phases consisted of five drugs (vincristine, prednisone, l-asparaginase, daunorubicin, and cyclophosphamide). Initial consolidation comprised six-agent chemotherapy combined with 18 Gy of total-brain irradiation. Patients were randomly assigned to receive G-CSF (5 μg/kg/day) during either induction or initial consolidation. A crossover study analysis was done on the 259 patients who completed both phases of therapy. Results: The mean time to neutrophil recovery (≥ 0.5 × 109/L) was reduced with G-CSF (16.7 v 19.1 days, P = .0003); however, patients who received G-CSF did not have significantly reduced episodes of febrile neutropenia (149 v 164, P = .41), positive blood cultures (57 v 61, P = .66), or serious infections (75 v 79, P = .62). Hospitalization (14.0 v 13.9 days, P = .87) and induction therapy completion times (NY I, 30.3 v 31.3 days, P = .11; NY II, 33.4 v 32.3 days, P = .40) were not significantly altered. There were no differences in 6-year EFS (P = .24) or OS (P = .54) between patients receiving or not receiving G-CSF on CCG-1901, NY I and NY II. Conclusion: Children with high-risk ALL do not appear to benefit from prophylactic G-CSF.
16
Faria, Leandro N., Antônio A. Soares In memoriam, Sérgio L. R. Donato, Marcelo R. dos Santos, and Luciana G. Castro. "The effects of irrigation management on floral induction of ‘Tommy Atkins' mango in bahia semiarid." Engenharia Agrícola 36, no. 3 (June 2016): 387–98. http://dx.doi.org/10.1590/1809-4430-eng.agric.v36n3p387-398/2016.
Анотація:
ABSTRACT This study aimed to evaluate reduction strategies of irrigation for proper management of floral induction and production of 'Tommy Atkins' mangoes, in the semiarid region of the Bahia state, Brazil. Five treatments with reduced irrigation levels based on crop evapotranspiration (ETc) were applied in two development stages, FI - flowering and FII – fruiting. Water depths were T1 - 0% of ETc in FI and 100% in FII; T2 - 25% of ETc in FI and 100% in FII; T3 - 50% of ETc in FI and 100% in FII; T4 - 75% of ETc in FI and 100% in FII; and T5 - 100% of ETc in FI and FII. The treatments were arranged in a randomized complete block design with six replications. Photosynthesis and transpiration rates in phases FI and FII were larger at 8 am than at 2 pm, regardless of the strategies used. These strategies lead to smaller values of photosynthesis, transpiration and leaf water potential within flowering stage. Productive characteristics were not affected by irrigation level reduction for flower induction process, only for the cycles evaluated. Strategies with 0% of ETc in FI and 100% in FII or 25% of ETc in FI and 100% in FII are appropriate to flower induction in 'Tommy Atkins' mango.
17
Tousizadeh, Mahdi, Amirmehdi Yazdani, Hang Seng Che, Hai Wang, Amin Mahmoudi, and Nasrudin Abd Rahim. "A Generalized Fault Tolerant Control Based on Back EMF Feedforward Compensation: Derivation and Application on Induction Motors Drives." Energies 16, no. 1 (December 21, 2022): 51. http://dx.doi.org/10.3390/en16010051.
Анотація:
In this paper, a fault-tolerant three-phase induction drive based on field-oriented control is studied, and an analytical approach is proposed to elucidate the limitations of FOC in flux-torque regulation from the controller perspective. With an open-phase fault, the disturbance terms appear in the controller reference frame and degrade the controller performance when operating in a d-q plane with DC quantities. In addition, the hardware reconfiguration, which is essential to operate faulted three-phase drives, causes substantial change in the way the control parameters vd, vq are reflected onto the machine terminals. An accurate understanding of the feedforward term, by considering the open-phase fault and the hardware modifications, is provided to re-enable the FOC in presence of an open-phase fault. Furthermore, the concept of feedforward term derivation is generically extended to cover multiphase induction drives encountering an open-phase fault whereby no hardware reconfiguration is intended. The proposed method is explained based on a symmetrical six-phase induction and can be extended to drives with a higher number of phases. The effectiveness of the proposed derivation method, which is required to form a feedforward fault-tolerant controller, is verified and compared through the simulation and experiment, ensuring smooth operation in postfault mode.
18
Stein, Sebastian, and Rainer Pöttgen. "Rows of corner- and face-sharing Mg4 tetrahedra arranged as hexagonal rod packing in the hexagonal Laves phases REMg2 and the rare earth-rich phases RE9CoMg4 (RE=Y, Dy-Tm, Lu)." Zeitschrift für Kristallographie - Crystalline Materials 233, no. 9-10 (September 25, 2018): 607–13. http://dx.doi.org/10.1515/zkri-2017-2124.
Анотація:
Abstract Six new rare earth metal-rich intermetallic compounds RE9CoMg4 with RE=Y, Dy, Ho, Er, Tm and Lu were synthesized by induction-melting the elements in sealed niobium ampoules followed by annealing in muffle furnaces. The structures of Y9CoMg4 and Tm8.56CoMg4.44 were refined from single-crystal X-ray diffraction data: P63/mmc, a=965.65(6), c=971.07(5) pm, wR2=0.0599, 614 F2 values, 20 variables for Y9CoMg4 and a=945.20(4), c=953.11(5) pm, wR2=0.0358, 585 F2 values, 21 variables for Tm8.56CoMg4.44 (a small homogeneity range results from Tm/Mg mixing). The RE9CoMg4 phases crystallize with a coloring variant of the aristotype Co2Al5. The striking structural motif is a hexagonal rod packing of rows of corner- and face-sharing tetrahedral Mg4 clusters with Mg–Mg distances ranging from 304 to 317 pm in Y9CoMg4. These rows are similar to the hexagonal Laves phases REMg2. The space between the rows is filled with rows of face-sharing Co@Y6 trigonal prisms (TP) and empty Y6 octahedra (O) in the sequence –TP–O–O–. The many isopointal coloring variants of the aristotype Co2Al5 are briefly discussed.
19
Hauschildt, Katja, Andreas Stark, Hilmar Burmester, Ursula Tietze, Norbert Schell, Martin Müller та Florian Pyczak. "Phase Transformations in the Brazing Joint during Transient Liquid Phase Bonding of a γ-TiAl Alloy Studied with In Situ High-Energy X-Ray Diffraction". Materials Science Forum 941 (грудень 2018): 943–48. http://dx.doi.org/10.4028/www.scientific.net/msf.941.943.
Анотація:
TiAl alloys are increasingly used as a lightweight material, for example in aero engines, which also leads to the requirement for suitable repair techniques. Transient liquid phase bonding is a promising method for the closure of cracks (in non-critical or non-highly loaded areas). The brazing solder Ti-24Ni was investigated for brazing the alloy Ti-45Al-5Nb-0.2B-0.2C (in at. %). After brazing, the joint exhibits different microstructures and phase compositions. The transient liquid phase bonding process was investigated in the middle of the joint region in situ to acquire time resolved information of the phases, their development, and thus the brazing process. These investigations were performed using high-energy X-ray diffraction at the “High-Energy Materials Science” beamline HEMS, located at the synchrotron radiation facility PETRA III at DESY in Hamburg, Germany. For this, we used an induction furnace, which is briefly described here. During the analysis of the diffraction data with Rietveld refinement, the amount of liquid was refined with Gaussian peaks and thus could be quantified. Furthermore, while brazing four different phases occurred in the middle of the joint region over time. Additionally, the degree of ordering of the βo phase was determined with two ideal stoichiometric phases (completely ordered and disordered). Altogether, the phase composition changed clearly over the first six hours of the brazing process.
20
Kawasaki, Hirohide, Souichi Adachi, Akira Ohara, Atsushi Kikuta, Atsushi Sato, Hiroyuki Takahashi, Motoaki Chin, et al. "Minimal Risidual Disease monitoring in Childhood Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia: Preliminary Results of JPLSG Ph+ALL04." Blood 114, no. 22 (November 20, 2009): 4116. http://dx.doi.org/10.1182/blood.v114.22.4116.4116.
Анотація:
Abstract Abstract 4116 Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) is very rare and poor prognostic condition in children. Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) conducted first nationwide clinical trial for Ph+ALL in children (Ph+ALL04). Ph+ALL04 consists of five therapy phases; Induction phase (five drugs induction), Intensification phase (high-dose CA and BFM Ib), Re-induction phase (four drugs re-induction), Imatinib mono-therapy phase, and hematopoietic stem cell transplantation phase (VP+CY+TBI condioning). Before and after each phase, BCR-ABL minimal residual disease (MRD) was monitored by the real-time PCR method. During the period 2004-08, 44 patients were enrolled in the Ph+ALL04 study. Out of 44 patients, five were resistant to Induction Phase and did not achieve CR. Their levels of BCR-ABL transcript at diagnosis were significantly higher than that of patients achieved CR after Induction phase. After Induction phase, 39 patients achieved CR, and seven of 39 patients also achieved MRD negative. After Intensification phase, two patients relapsed. Thirty-four patients were still in CR, and 10 patients also achieved MRD negative after Intensification phase. One patient relapsed after Re-induction phase and three patients relapsed after Imatinib mono-therapy phase. Thirteen patients were MRD negative before Imatinib mono-therapy phase, and 14 patients were MRD negative after Imatinib mono-therapy phase. Before Hematopoietic stem cell transplantation phase, 14 patients were MRD negative. Twenty-six patients received hematopoietic stem cell transplantation. Out of 26 patients, three relapsed after hematopoietic cell transplantation. Twenty-three patients continued to be in CR and MRD negative for median 2 years after hematopoietic stem cell transplantation. In conclusion, amount of BCR-ABL transcript is a possible predictor for achieving remission after induction therapy in Ph+ALL children. MRD detection during therapy is confirmed the important prognostic indicator in the context of the intensive chemotherapy and hematopoietic stem cell transplantation in Ph+ALL children. Disclosures: No relevant conflicts of interest to declare.
21
Keller, Emanuela, Thorsten Steiner, Javier Fandino, Stefan Schwab, and Werner Hacke. "Changes in cerebral blood flow and oxygen metabolism during moderate hypothermia in patients with severe middle cerebral artery infarction." Neurosurgical Focus 8, no. 5 (May 2000): 1–4. http://dx.doi.org/10.3171/foc.2000.8.5.4.
Анотація:
Object Moderate hypothermia has been reported to be effective in the treatment of postischemic brain edema. The effect of hypothermia on cerebral hemodynamics is a matter of controversial discussion in literature. Clinical studies have yet to be performed in patients with ischemic stroke after induction of hypothermia. Methods Measurements during mild hypothermia (33–34°C) were made in six patients with severe ischemic stroke involving the middle cerebral artery territory. Hypothermia was induced as soon as possible and maintained for 48 to 72 hours. Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were estimated by a new double-indicator dilution method. Measurements of CBF were made during normothermia, immediately after induction of hypothermia, at the end of hypothermia, and after rewarming. A total of 19 measurements of CBF and jugular bulb O2 saturation were made. Immediately after induction of hypothermia, CBF decreased in all patients. During late hypothermia, CBF improved in patients who survived but remained diminished in the two patients who died. Reduced CMRO2 levels were observed during all phases of hypothermia in all but one case. Conclusions Preliminary oberservations indicate that moderate hypothermia seems to reduce CMRO2 Immediately after induction of hypothermia, CBF may decrease in all patients. During late hypothermia CBF seems to recover in patients with good outcome but remains diminished in patients who die. Serial bedside CBF measurements with the new double-indicator dilution technique may be useful to describe cerebral hemodynamic characteristics in patients with severe ischemic stroke during hypothermia.
22
Jelbaoui, Yakout Khadouj, Lamiaa El Menzhi, and Abdallah Saad. "Diagnosis of rotor faults by fast Fourier transform using an auxiliary winding voltage." Indonesian Journal of Electrical Engineering and Computer Science 24, no. 2 (November 1, 2021): 680. http://dx.doi.org/10.11591/ijeecs.v24.i2.pp680-688.
Анотація:
<p>Condition monitoring and on-line detection have attracted several researchers in order to carry out an efficient diagnosis of machine failures. Therefore, the detection in early stage avoids system breakdown and reduce the maintenance cost. This paper presents a new diagnosic approach to detect the broken bars and broken end ring faults for a squirrel cage induction machine based on the fast Fourier transform analysis applied on a new signature as the voltage of an auxiliary winding. The auxiliary winding is a small coil inserted between two of the stator phases, the explicit expression of its voltage is presented. The signal is monitored in six faults cases under a different load level, the emergence of the fault frequencies changes for each kind of failure. The successfully simulation results obtained show the effectiveness of this approach.</p>
23
Lipinskis, Tadas. "ANALYSIS OF VOLTAGE FORMING METHODS FOR MULTIPHASE INVERTERS / DAUGIAFAZIŲ DAŽNIO KEITIKLIŲ ĮTAMPOS FORMAVIMO METODŲ ANALIZĖ." Mokslas - Lietuvos ateitis 5, no. 2 (May 24, 2013): 119–23. http://dx.doi.org/10.3846/mla.2013.22.
Анотація:
The article discusses advantages of the multiphase AC induction motor over three or less phase motors. It presents possible stator winding configurations for a multiphase induction motor. Various fault control strategies were reviewed for phases feeding the motor. The authors propose a method for quality evaluation of voltage forming algorithm in the inverter. Simulation of a six-phase voltage source inverter, voltage in which is formed using a simple SPWM control algorithm, was performed in Matlab Simulink. Simulation results were evaluated using the proposed method. Inverter’s power stage was powered by 400 V DC source. The spectrum of output currents was analysed and the magnitude of the main frequency component was at least 12 times greater than the next biggest-magnitude component. The value of rectified inverter voltage was 373 V. Article in Lithuanian. Santrauka Straipsnyje pristatomi daugiafazių variklių pranašumai, palyginus su trifaziais ir vienfaziais. Apžvelgiama variklių sandara ir pristatomi daugiafazių variklių apvijų tipai. Pristatomos variklių valdymo strategijos sugedus apvijos ar inverterio galios pakopos raktui. Pasiūloma daugiafazių dažnio keitiklių įtampos formavimo algoritmų vertinimo metodika. Matlab Simulink terpėje modeliuojamas šešiafazis dažnio keitiklis, kuriame veikia sinusinio impulso skvarbos moduliavimo įtampos formavimo algoritmas. Pagal sukurtą vertinimo metodiką įvertinami dažnio keitiklio modeliavimo rezultatai, pateikiamos išvados.
24
Dunphy, F. R., G. Spitzer, A. U. Buzdar, G. N. Hortobagyi, L. J. Horwitz, J. C. Yau, J. A. Spinolo, S. Jagannath, F. Holmes, and R. O. Wallerstein. "Treatment of estrogen receptor-negative or hormonally refractory breast cancer with double high-dose chemotherapy intensification and bone marrow support." Journal of Clinical Oncology 8, no. 7 (July 1990): 1207–16. http://dx.doi.org/10.1200/jco.1990.8.7.1207.
Анотація:
We have used high-dose therapy followed by randomization to receive or not receive autologous bone marrow infusion in 58 stage IV breast cancer patients (all were estrogen receptor-negative [ER-] or primary hormonal refractory). Patients received a median of four courses of induction chemotherapy and if stable or responding received two courses of intensive therapy with cyclophosphamide 4.5 to 5.25 g/m2, etoposide 750 to 1,200 mg/m2, and cisplatin 120 to 180 mg/m2 (CVP). The complete remission (CR) rate after completion of the induction and intensive phases was 55%. Median progression-free interval from induction is 57 weeks with a projected 2-year progression-free survival of approximately 25%. Six of seven patients followed for greater than 2 years are still progression-free. Three favorable features predicted for improved progression-free survival are the following: (1) absent liver involvement, (2) absent soft tissue involvement, and (3) less than or equal to two disease sites (P values of .001, .013, and .048, respectively). Hormonal and menopausal status did not predict for progression-free survival. Major toxicities were infectious secondary to neutropenia, with a 93% incidence of fever and a 38% incidence of sepsis. The treatment-related mortality rate was 9%, with three infectious, one coronary, and one late hemorrhage-related death of unknown cause. Longer follow-up is still needed to truly evaluate the possibility of long-term disease-free survival, but further studies of this approach to high-dose intensification in poor prognostic groups of stage IV breast cancer appear warranted.
25
Bowen, Jennifer M., Geoffrey E. Dahl, Neil P. Evans, Lori A. Thrun, Yuedong Wang, Morton B. Brown, and Fred J. Karsch. "Importance of the Gonadotropin-Releasing Hormone (GnRH) Surge for Induction of the Preovulatory Luteinizing Hormone Surge of the Ewe: Dose-Response Relationship and Excess of GnRH*." Endocrinology 139, no. 2 (February 1, 1998): 588–95. http://dx.doi.org/10.1210/endo.139.2.5719.
Анотація:
Abstract The preovulatory LH surge in the ewe is stimulated by a large sustained surge of GnRH. We have previously demonstrated that the duration of this GnRH signal exceeds that necessary to initiate and sustain the LH surge. The objective of the present study was to determine whether a similar excess exists for amplitude of the GnRH surge. Experiments were performed using an animal model in which GnRH secretion was blocked by progesterone, which in itself does not block the pituitary response to GnRH. To assess the amplitude of the GnRH surge needed to induce the LH surge, we introduced artificial GnRH surges of normal contour and duration but varying amplitudes. Twelve ewes were run through 3 successive artificial follicular phases (total of 36). Six of these artificial follicular phases were positive controls, in which progesterone was removed, the estradiol stimulus was provided, and vehicle was infused. In these control cycles, animals generated endogenous LH surges. In the remaining artificial follicular phases, progesterone was not withdrawn, the estradiol stimulus was provided, and either vehicle (negative control) or GnRH solutions of varying concentrations (experimental) were infused. The circulating GnRH concentrations achieved by infusion were monitored. No LH surges were observed in negative controls, whereas LH surges were induced in experimental cycles provided a sufficient dose of GnRH was infused. A highly significant dose-response relationship was observed between the amplitude of the GnRH surge and both the amplitude of the LH surge and the area under the curve describing the LH response, but no such relationship existed between the amplitude of the GnRH surge and the duration of the LH response. In numerous cases, LH surges similar to those in the positive control animals resulted from infusion of amounts of GnRH estimated to be considerably less than those delivered to the pituitary during the endogenously generated GnRH/LH surge. These findings indicate that, in the ewe, increased GnRH secretion drives the preovulatory LH surge in a dose-dependent fashion, and they provide evidence that the amplitude of the GnRH surge may exceed that needed to generate the LH surge.
26
Kantarjian, H. M., M. Talpaz, D. Kontoyiannis, J. Gutterman, M. J. Keating, E. H. Estey, S. O'Brien, M. B. Rios, M. Beran, and A. Deisseroth. "Treatment of chronic myelogenous leukemia in accelerated and blastic phases with daunorubicin, high-dose cytarabine, and granulocyte-macrophage colony-stimulating factor." Journal of Clinical Oncology 10, no. 3 (March 1992): 398–405. http://dx.doi.org/10.1200/jco.1992.10.3.398.
Анотація:
PURPOSE The study was undertaken to improve the results of intensive chemotherapy in chronic myelogenous leukemia (CML) in accelerated (CML-AP) and blastic phases (CML-BP) by the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) as supportive therapy. PATIENTS AND METHODS Forty-eight patients were treated with daunorubicin 120 mg/m2 intravenously on day 1, cytarabine (ara-C) 1.5 g/m2/d by continuous infusion over 24 hours for 4 days, and Solu-Medrol (methylprednisolone; The Upjohn Co, Kalamazoo, MI) 100 mg/d for 5 days, followed on day 5 by GM-CSF 125 micrograms/m2/d over 6 hours until recovery of granulocyte count above 2.0 x 10(3)/microliters. Twenty-four patients had CML-BP, and 24 had CML-AP. RESULTS During remission induction, 45 patients (94%) developed febrile episodes (fever of unknown origin, 23 patients [48%]; documented infections, 22 patients [46%]). The median time to recovery of granulocyte count above 0.5 x 10(3)/microliters was 29 days and to platelet count above 30 x 10(3)/microliters, 28 days. Overall, 14 of 48 patients (29%) achieved a complete hematologic remission (CHR), and seven (15%) reverted to a second chronic phase. CHR was noted in eight of 24 patients with CML-BP (33%), and in six of 24 patients with CML-AP (25%). Cytogenetic responses were observed in 11 patients (23%), but were transient. Sixteen patients developed either fluid retention, hypotension, pleuropericardial effusions, or pericarditis, or a combination of these side effects. These side effects were severe in four patients and are likely to be disease-associated, as a similar regimen of intensive chemotherapy and GM-CSF at the same dose and schedule in acute lymphocytic leukemia was not associated with these side effects. CONCLUSIONS The results pertinent to remission rates, induction mortality, myelosuppression profile and related complications, and overall survival were not significantly improved compared with previous experience. In summary, the results of intensive chemotherapy in CML-transformed phases remain poor, despite the addition of GM-CSF as a supportive measure.
27
Zahri, Abdul, Agus Oman Sudrajat, and Muhammad Zairin Junior. "Profil hormon FSH, LH dan estradiol serta kadar glukosa darah sidat, Anguilla bicolor bicolor (Mc Clelland, 1844) yang dirangsang hormon HCG, MT, E2 dan anti dopamin." Jurnal Iktiologi Indonesia 18, no. 1 (June 25, 2018): 57. http://dx.doi.org/10.32491/jii.v18i1.374.
Анотація:
This study aims to analyze the hormone profile of FSH, LH and E2 to the eel after exogenous hormone stimulation and blood glucose levels. Six formulated treatment applied with combination of dopamine antagonize 10 mg.mL–1 (A), estradiol (E2) 3 mg.mL–1 + A (EA), metyltestosteron (MT) 3 mg.mL–1 + A (MTA), hCG 2 mg.mL–1 + EA (hEA) and hCG 2 mg.mL–1 + MTA (hMTA), with (F) physiologis 0.9% NaCl to control. Six group eel (200±15g) reared in a concrete tank with a capacity of 3,400 liters and filled with sea water of 35 mg L–1 as much as 2000 liters. Eels injected 1 mL.kg–1 hormone by intramusculary, were feed to apparent satiation daily for 10 weeks. The study used Completely Randomized Design with one treatment factor, namely hormonal factor and its combination. Fish blood that ware directly concentration to FSH, LH and E2, the enhanced significantly high in the blood plasma on treatment hMTA and hEA P<0.05. Glucose concentration in the blood palsma is high enough in a row on a formula hMTA 67.33 mg.dL–1 and significantly different to P<0.05. The result indicates that induction of exogenous hormone (hMTA) improve FSH, LH and E2. FSH and LH profiles show permutation patterns during the development of eel gonad, beginning with the increase of FSH in the early phases of gonadal development. LH profile moves in line with the increase in E2 during gonadal maturation process eels (A. bicolor bicolor), with blood glucose levels in the normal range. AbstrakThis study aims to analyze the hormone profile of FSH, LH and E2 to the eel after exogenous hormone stimulation and blood glucose levels. Six formulated treatment applied with combination of dopamine antagonize 10 mg.mL–1 (A), estradiol (E2) 3 mg.mL–1 + A (EA), metyltestosteron (MT) 3 mg.mL–1 + A (MTA), hCG 2 mg.mL–1 + EA (hEA) and hCG 2 mg.mL–1 + MTA (hMTA), with (F) physiologis 0.9% NaCl to control. Six group eel (200±15g) reared in a concrete tank with a capacity of 3,400 liters and filled with sea water of 35 mg L–1 as much as 2000 liters. Eels injected 1 mL.kg–1 hormone by intramusculary, were feed to apparent satiation daily for 10 weeks. The study used Completely Randomized Design with one treatment factor, namely hormonal factor and its combination. Fish blood that ware directly concentration to FSH, LH and E2, the enhanced significantly high in the blood plasma on treatment hMTA and hEA P<0.05. Glucose concentration in the blood palsma is high enough in a row on a formula hMTA 67.33 mg.dL–1 and significantly different to P<0.05. The result indicates that induction of exogenous hormone (hMTA) improve FSH, LH and E2. FSH and LH profiles show permutation patterns during the development of eel gonad, beginning with the increase of FSH in the early phases of gonadal development. LH profile moves in line with the increase in E2 during gonadal maturation process eels (A. bicolor bicolor), with blood glucose levels in the normal range.
28
Joseph, Kouadio Natia, Assoumou Ebah Carine, Cisse Mariam, Kouadio Ange Laetitia Jocelyne, Offng Marie Josiane Agnei, Gnahoue Goueh, and Kra Kouassi Aboutou Severin. "Effect of PASLoc Meals on the Zootechnical and Nutritional Parameters of Young Wistar Rats Suffering from Induced Moderate Acute Malnutrition." Annual Research & Review in Biology 39, no. 6 (May 24, 2024): 31–40. http://dx.doi.org/10.9734/arrb/2024/v39i62086.
Анотація:
Aims: The objective of this study was to assess the efficacy of four food products manufactured from locally sourced ingredients in restoring Wistar rats afflicted with induced moderate acute malnutrition. Study Design: The rats used in this research were kept in separate metabolic cages with wire mesh flooring. Place and Duration of Study: The study was conducted at the vivarium of the Ecole Normale Supérieure in Abidjan, Côte d'Ivoire, over a period of 38 days. Methodology: 42 male rats, with an average age of 80 ±5 days and an average weight of 103.46 ±5.10 g, were randomly divided into six batches of seven rats each. Two control batches (MID and PCD) and four experimental batches (PASLoc1A, PASLoc1B, PASLoc2A, and PASLoc2B) were formed. The experiment consisted of an adaptation phase (5 days), a malnutrition induction phase (19 days), and a nutritional rehabilitation phase (14 days). Zootechnical and nutritional parameters were assessed at the end of the induction and nutritional rehabilitation phases. Results: Malnourished animals experienced a body weight loss rate of -22.36 ±6.47%, leading to a decline in all zootechnical parameters, including weight gain (1.39 ±0.28 g/day), body length (0.95 ±0.64 cm), and feed efficiency coefficient (-24.98 ±5.47). The nutritional rehabilitation phase resulted in the correction of the dysfunctions observed during induction, especially in terms of body weight gain, with rates comprised between 20.84 ±5.03% and 34.59 ±3.33%. The minimum weight gain for the rats fed PASLoc diet was 1.66 ±0.54 g/d for Pasloc1B, respectively. PASLoc diets have a significant impact on nutritional value, with a minimum biological value of 94.04 ±0.25%. Conclusion: The result of this study suggest that PASLoc2A and PASLoc2B possess a robust nutritional potential, and their consumption can effectively address issues of moderate acute malnutrition after weaning.
29
Beladel, Abdelkader, Abdellah Kouzou, Mohamed Elbar, and Ahmed Hafaifa. "DTC Switching Strategy for Open-end Winding of Induction Machines Fed by a Dual-output Indirect Matrix Converter." Periodica Polytechnica Electrical Engineering and Computer Science 65, no. 3 (June 7, 2021): 186–95. http://dx.doi.org/10.3311/ppee.17597.
Анотація:
This paper deals with the Direct Torque Control (DTC) of Dual Indirect Matrix Converter (DIMC) feeding an open-end winding three-phase Induction Motor (IM). Indeed, the open-end winding topology allows overcoming the main problem of Common-Mode Voltage (CMV) which is responsible of presence of stresses in the motor winding in classical topologies, controlling separately the winding of the three-phases, reducing the voltage stress of the power electronics switches and to decreasing the voltage and current harmonics in each phase. The proposed Dual-output Indirect Matrix Converter generates 18 active voltage space vectors. Whereas, in the proposed algorithm presented in this paper to ensure the control of the proposed topology it is implemented only with two null vectors and six active voltage vectors for each output. It is based on same idea of the space vector pulse width modulation that is applied separately for both converters to ensure the control of their output voltages. Indeed, to ensure the required voltage at each winding the output voltage of the first matrix converter are generated normally and output voltage of the second matrix converter are generated with 180° phase shift. The obtained simulation results prove clearly the overall performance of the control of the studied drive system based on the proposed topology and its control algorithm which may be extended to other drive system application, especially in industrial application where more improved performances are required.
30
Manabe, Atsushi, Hirohide Kawasaki, Motoaki Chin, Atsushi Sato, Kimikazu Matsumoto, Tsutomu Watanabe, Michiko Kajiwara, et al. "A Brief Use of Imatinib Immediately Before Hematopoietic Stem Cell Transplantation (HSCT) in Children with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL). Results of the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) Study Ph+ALL04." Blood 118, no. 21 (November 18, 2011): 2554. http://dx.doi.org/10.1182/blood.v118.21.2554.2554.
Анотація:
Abstract Abstract 2554 Aims: Children with Ph+ALL generally have a poor prognosis when treated with chemotherapy alone. The timing and duration of the use of imatinib has not been determined. We investigated a role of imatinib immediately before HSCT. Methods: All the patients with ALL were screened for diagnosis of Ph+ALL using RT-PCR. Children with Ph+ALL were enrolled on JPLSG Ph+ALL04 Study within 1 week of initiation of treatment for ALL. Treatment regimen consisted of 5 therapeutic phases: Induction phase (5-drug induction), Intensification phase (high-dose cytarabine and BFM Ib), Re-induction phase (4-drug re-induction), 2 weeks of Imatinib monotherapy phase (23 weeks after diagnosis), and HSCT phase (Etoposide+CY+TBI conditioning). Before and after each phase, minimal residual disease (MRD), the amount of BCR-ABL transcripts, was measured with the real-time PCR method (cut-off 50 copies/microgram RNA). The study was registered in UMIN-CTR (Medical Information, University hospital Medical Information Network - Clinical Trials Registry): UMIN ID C000000290. Results: During the period 2004–08, 42 patients were registered in the Ph+ALL04 study. Out of 42 patients, 37 patients (88%) achieved CR and 7 of 37 patients also achieved MRD-negative after induction phase. There were 13 patients who had no MRD at the beginning of imatinib monotherapy phase, and 14 patients were MRD-negative after imatinib phase, consequently, 14 patients were MRD-negative at the time of HSCT. Six patients relapsed before HSCT. In total, 31 patients received HSCT in 1st CR. All the patients had engraftment and no patients died because of complications of HSCT. Five patients relapsed after HSCT and 4 of the 5 patients were MRD-negative before HSCT and the other patient had detectable MRD although it was less than 50 copies. Twenty-six patients continue to be in 1st CR and MRD-negative for median of 3 years after diagnosis. The 3-year event-free survival rate and over-all survival rate for all the patients was 57% and 80%, respectively (figure 1). Five patients did not achieve CR after induction phase and they were treated with imatinib-contained chemotherapy. Four of the 5 patients achieved CR. All of the 4 patients received cord blood transplantation and remains in continued CR. Interpretation: The chemotherapy we employed was based on the previous high-risk regimen of TCCSG (Tokyo Children's Cancer Study Group) L-99-15 Study. The chemotherapy was intensive enough to induce MRD-negative in 13 at the time of imatinib phase and 31 of 42 patients were in CR at the time of HSCT (around 25–28 weeks after diagnosis). We planned to assess the efficacy of imatinib immediately before HSCT but it was not possible because of the low amount of MRD in most patients at the beginning of imatinib phase. Conclusion: Although EFS and OS was excellent in this study, 88% of induction rate appeared unsatisfactory and relapse occurred before HSCT in 6 out of 37 patients who achieved CR after induction phase. Earlier and longer use of imatinib may improve EFS in children with Ph+ALL and HSCT may be omitted in a subset of patients who achieve an early and deep remission status. Disclosures: No relevant conflicts of interest to declare.
31
Isjanovski, Viktor, and Igor Isjanovski. "Comparison of the Use of Hypnotic in Psychiatric Patients with Insomnia at the Mental Health Centre Prolet in Skopje." Open Access Macedonian Journal of Medical Sciences 7, no. 17 (September 1, 2019): 2786–90. http://dx.doi.org/10.3889/oamjms.2019.711.
Анотація:
BACKGROUND: Insomnia is a symptom complex that comprises difficulties falling asleep, staying asleep or non-refreshing sleep in combination with daytime dysfunction or distress. Most people experience insomnia at some time during their lives. Because of its high incidence, and also because its symptoms are usually mild and transient, the importance of insomnia is frequently underestimated. Various conditions are associated with insomnia and can contribute to its development. They can be related to neurological or psychiatric disorders, which in turn may be aggravated by a deficiency of restorative sleep and daytime fatigue.
AIM: In this study, the authors compare the hypnotically effect of Flurazepam and Zolpidem applied on psychiatric cases treated in the Mental Health Centre “Prolet” in Skopje, Republic of Macedonia.
METHODS: The investigation covers 45 patients who have insomnia, in addition to their primary mental illness. Тhe examination took six weeks, and it was divided into 3 equal phases. In the first phase of three weeks, Zolpidem was used, and in the third phases, Flurazepam was administrated. We used a self-estimating scale of 13 items and methods of global clinical estimation in the evaluation of received effects.
RESULTS: The results show that referring to the induction of the sleeping period, its duration and quality and the number of awakenings, there are no significant differences between the two medicaments used, but there was a significant difference between hypnotic medicaments and placebo.
CONCLUSION: The termination with the therapy, didn`t lead to the appearance of abstinential symptoms.
32
Paolini, Stefania, Sarah Parisi, Ilaria Iacobucci, Cristina Papayannidis, Maria Chiara Abbenante, Antonio Curti, Emanuela Ottaviani, Nicoletta Testoni, Michele Baccarani, and Giovanni Martinelli. "Pediatric Therapy In Adult Acute Lymphoblastic Leukemia: Updated Experience of a Single Centre." Blood 116, no. 21 (November 19, 2010): 4338. http://dx.doi.org/10.1182/blood.v116.21.4338.4338.
Анотація:
Abstract Abstract 4338 Background. Acute lymphoblastic leukemia (ALL) presents with different outcome in children and adults, with event-free-survival (EFS) rates of 70–80% and 30–40% at 5 years, respectively. This reflects both a different disease biology and different therapeutic approaches. Recently, results apparently improved in young adults/adolescents aged 15–21 years, with de novo ALL, when treated with pediatric intensive regimens rather than with typical adult regimens. Similarly, clinical studies are ongoing in older patients, toxicity related-therapy seeming the limiting issue. Aims. We report a single centre experience on adult ALL patients treated with an intensive pediatric-inspired schedule, designed to assess its tolerability and efficacy. Methods. From November 2007 to June 2010 seventeen ALL patients (M/F=12/5) were treated at our Center according to a modified AIEOP LAL2000 regimen. Treatment consisted of 7 days steroid pre-treatment, and four drugs 78-days induction (phase IA and phase IB) after which high risk (HR) patients were treated with three polychemotherapy blocks, while intermediate (IR) and standard risk (SR) patients went on 8-weeks consolidation and subsequent delayed intensification. Allo-SCT was planned for all patients with HLA-matched donor, as alternative to 2-years maintenance therapy. Median age was 31 years (range, 17–47). According to cytogenetic, response to steroid and minimal residual disease patients were classified into HR (n=7), IR (n=6) and SR (n=4). Results. 15/17 patients completed the induction phase IA, two being out for toxicity (grade IV infection and intestinal occlusion). Twelve (71%) obtained a complete remission (CR); three were refractory. However, one of them subsequently achieved CR after polychemotherapy blocks, for an overall response rate of 76% (13/17). Eleven patients then completed the 28-days induction IB. One patient is ongoing. Median induction duration was 92 days (range 82–136). Delays were mostly due to extra-hematological toxicity, the commonest being gastrointestinal (n=12), infective (n=7) and thrombotic (n=3). Delays were accumulated in both induction phases without significant difference between phase IA (median 18.5 days, range 4–37) and phase IB (median 17 days, range 9–66), despite an absolute number of moderate-severe AE superior in phase-IA versus phase-IB (12 vs 5). After induction, 4/12 patients already received consolidation therapy; 2/4 then received allo-SCT. The median duration of consolidation was 51 days (range 22–94). Conversely, 6/12 patients received polychemotherapy-blocks, one patient went directly on alloSCT and the remaining is ongoing. After polychemotherapy-blocks, five out six patients received allo-SCT. The median CR duration was 13 months (range 1+-42+); two patients relapsed, both after allo-SCT. With a median follow-up of 11 months (range 2–43) 11/17 (65%) patients are alive, 9 in CR (5 undergone allo-SCT). Six patients dead, three in CR for infectious complications, 3 for relapsed/refractory disease. Conclusions. Though in a small series, pediatric-like intensive chemotherapy seemed to be feasible in adult ALL. Extra-hematological toxicity, however, caused significant treatment delays during induction. Finally, the overall outcome appeared promising, though longer follow-up and larger populations are needed to draw definitive conclusions. Acknowledgments. BolognAIL, European LeukemiaNet, AIRC, Fondazione Del Monte di Bologna e Ravenna, FIRB 2006, PRIN 2008, Ateneo RFO, Project of Integrated Program (PIO), Programma di Ricerca Regione – Università 2007–2009. Disclosures: No relevant conflicts of interest to declare.
33
Shulman, David S., Preeti Mehrotra, Neeraj K. Surana, Traci M. Blonquist, Lewis B. Silverman, and Andrew E. Place. "Bacillus Infection Among Children with Hematologic Malignancy, a Single Institution Experience." Blood 126, no. 23 (December 3, 2015): 1292. http://dx.doi.org/10.1182/blood.v126.23.1292.1292.
Анотація:
Abstract BACKGROUND: Bacillus species, including B. cereus and other non-anthracis species, are spore-forming, gram-positive rods, found ubiquitously in the environment and cause bacteremia and CNS infection in children with cancer. Case reports have demonstrated that Bacillus spp. infections carry a high morbidity, with rates of CNS involvement of 30%, and mortality as high as 40%. These studies indicate the preponderance of cases occur in children receiving induction chemotherapy for acute lymphoblastic leukemia (ALL). There have been no large, recent studies describing Bacillus spp. infection in children with an underlying oncologic condition. METHODS: We performed a retrospective medical record review of pediatric cancer patients who received care at the Dana-Farber/Boston Children's Cancer and Blood Disorders Center and developed Bacillus spp. infection between January 1st, 2005 and December 31st 2014. Given that the majority of these infections were found to occur in children with underlying hematologic malignancy, we provide a more detailed description of cases with these underlying conditions. RESULTS: Twenty-six children developed Bacillus bacteremia during the study period. Of the 26 patients, 21 (81%) had acute leukemia (18 ALL; 3 AML), 3 had neuroblastoma, one had Ewing's sarcoma and one had an optic pathway glioma. The mean age of patients with hematologic malignancies at time of Bacillus spp. infection was 7.3 years [range: 1-17]. Sixteen (76%) children were neutropenic at the time of infection. Of the children with ALL, 11 (61%) developed infection during the remission induction phase of treatment, 3 during post-induction/pre-maintenance treatment phases and 3 after relapse (1 during stem cell transplant, 1 at a year post-transplant and 1 during re-induction). Of the 26 patients, 5 (19%) developed CNS complications, all during remission induction for ALL, and the overall mortality two-weeks following Bacillus infection was 19%. DISCUSSION: Bacillus spp. continues to cause serious infections in children with cancer, especially in those with underlying hematologic malignancies. While the mortality at our center is lower than that reported in the literature, the rate of death is still higher than what is typically seen with other organisms and CNS involvement remains common. Further study in this area will include identification of risk factors for development of this infection and recommendations regarding use of prophylactic antibiotics. Disclosures No relevant conflicts of interest to declare.
34
Zhao, Li, Shoudao Huang, Yuan Gao, and Jian Zheng. "A Common-Mode Voltage Suppression Strategy Based on Double Zero-Sequence Injection PWM for Two-Level Six-Phase VSIs." Energies 15, no. 17 (August 26, 2022): 6242. http://dx.doi.org/10.3390/en15176242.
Анотація:
A common-mode voltage (CMV) suppression strategy, namely double zero-sequence injection common-mode voltage (DZICMV), is proposed in this paper for an asymmetrical six-phase induction motor fed by two-level dual three-phase voltage source inverters (VSIs). In this strategy, the sinusoidal waveforms injected by double zero-sequence signals are employed as modulation signals, and two opposite triangular waveforms are used as carriers. The fundamental period is divided into 24 sectors. In each sector, the carrier used by the medium amplitude phase is distinct from the carriers used by the other two phases in each set of three-phase windings. Using this method, the zero vectors (000) and (111) in each set of three-phase windings can be eliminated, and the peak values of sub-CMV and total CMV can be reduced from ±Udc/2 to ±Udc/6. The experiment results show that the root mean square (RMS) value of common-mode leakage current in DZICMV can be reduced by 51.83% compared with the double zero-sequence injection PWM (DZIPWM) strategy. It is also found in the other four existing benchmark CMV suppression strategies that the peak values of sub-CMV therein are nearly all ±Udc/2, and only in the low linear modulation region could one of these strategies suppress sub-CMV peak values to ±Udc/6. However, the proposed DZICMV can suppress the sub-CMV peak values to ±Udc/6 in the whole linear modulation range. Moreover, the maximum linear modulation index of the DZICMV is 1.15, which is larger than that of the four benchmark strategies, whose maximum modulation index is 1.
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Vitolo, U., S. Cortellazzo, A. M. Liberati, R. Freilone, M. Falda, M. Bertini, B. Botto, et al. "Intensified and high-dose chemotherapy with granulocyte colony-stimulating factor and autologous stem-cell transplantation support as first-line therapy in high-risk diffuse large-cell lymphoma." Journal of Clinical Oncology 15, no. 2 (February 1997): 491–98. http://dx.doi.org/10.1200/jco.1997.15.2.491.
Анотація:
PURPOSE In our previous study with MACOPB, we identified a high-risk group of patients with a poor 3-year survival rate of 29%. These patients were defined as having at diagnosis advanced-stage disease with high tumor burden (TB) and elevated lactate dehydrogenase (LDH) level or bone marrow (BM) involvement. A novel therapeutic scheme was investigated to improve the outcome of these patients. PATIENTS AND METHODS Fifty patients with high-risk diffuse large-cell lymphoma (DLCL) were enrolled. The therapeutic scheme includes three phases: induction with 8 weeks of MACOPB; intensification with a 3-day course of mitoxantrone 8 mg/m2 plus high-dose cytarabine (HDARA-C) 2 g/m2 every 12 hours plus dexamethasone 4 mg/m2 every 12 hours (MAD protocol) and granulocyte colony-stimulating factor (G-CSF) 5 microg/kg on days 4 to 17 to harvest peripheral-blood progenitor cells (PBPC); consolidation with carmustine (BCNU), etoposide, ARA-C, and melphalan (BEAM) regimen; plus autologous stem-cell transplantation (ASCT) with PBPC, marrow, or both. RESULTS Thirty-six patients (72%) achieved a complete response (CR), 11 (22%) showed no response (NR), and three (6%) died of toxicity. Among the 22 PRs or NRs after the induction phase, 56% of patients achieved a CR with subsequent intensified therapy. With a median follow-up duration of 32 months, the overall survival and failure-free survival rates were 56% and 50%, respectively. The disease-free survival rate is 69% at 32 months. Leukapheresis after MAD and G-CSF yielded a median of 32 x 10(6)/kg CD34+ cells and 80 x 10(4)/kg granulocyte-macrophage colony-forming units (CFU-GM). Thirty-nine patients were autografted and 11 did not undergo ASCT: six because of disease progression, four due to toxicity, and one because of patient refusal. The median times to achieve engrafment were 11 days (range, 7 to 19) to a neutrophil count greater than 0.5 x 10(9)/L and 12 days (range, 8 to 60) to a platelet count greater than 50 x 10(9)/L. CONCLUSION This sequential scheme with intensified and high-dose chemotherapy with ASCT is feasible with moderate toxicity and may improve the outcome in high-risk DLCL.
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Ghanizada, Hashmat, Nanna Arngrim, Henrik Winther Schytz, Jes Olesen, and Messoud Ashina. "Carbon monoxide inhalation induces headache but no migraine in patients with migraine without aura." Cephalalgia 38, no. 13 (March 14, 2018): 1940–49. http://dx.doi.org/10.1177/0333102418765771.
Анотація:
Introduction Carbon monoxide is an endogenously produced signaling gasotransmitter known to cause headache and vasodilation. We hypothesized that inhalation of carbon monoxide would induce migraine-like attacks in migraine without aura patients. Methods In a randomized, double-blind, placebo-controlled crossover design, 12 migraine patients were allocated to inhalation of carbon monoxide (carboxyhemoglobin 22%) or placebo on two separate days. Headache and migraine characteristics were recorded during hospital (0–2 hours) and post-hospital (2–13 hours) phases. Results Six patients (50%) developed migraine-like attacks after carbon monoxide compared to two after placebo (16.7%) ( p = 0.289). The median time to onset of migraine-like attacks after carbon monoxide inhalation was 7.5 h (range 3–12) compared to 11.5 h (range 11–12) after placebo. Nine out of 12 patients (75%) developed prolonged headache after carbon monoxide. The area under the curve for headache score (0–13 hours) was increased after carbon monoxide compared with placebo ( p = 0.033). Conclusion Carbon monoxide inhalation did not provoke more migraine-like attacks in migraine patients compared to placebo, but induced more headache in patients compared to placebo. These data suggest that non-toxic concentrations of carbon monoxide had low potency in migraine induction and that the carbon monoxide inhalation model is not suitable to study migraine.
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Bergeron, Christophe, David Perol, Helene Pacquement, Yves Perel, Carole Coze, Virginie Gandemer, Jean P. Vannier, et al. "Treatment of Childhood T Cell Lymphoblastic Lymphoma (TLL), Results of the SFOP LMT96." Blood 106, no. 11 (November 16, 2005): 3326. http://dx.doi.org/10.1182/blood.v106.11.3326.3326.
Анотація:
Abstract After LMT81 and SFOP LMT89 protocols (both modified LSA2L2), the SFOP LMT96 was designed according to BFM 86 back bone (Reiter and al, J Clin Oncol, 13:359.1995). The aim of LMT96 protocol was to increase chemotherapy intensity early (day 8) and late (after the intensification phase). From February 1997 to December 2003, 83 unselected patients (pts) with newly diagnosed TLL were included in LMT96 protocol: classic corticosteroid prephase (d1 to d7); induction phase with Cyclophosphamide(CPM: 1g/m2) and high dose methotrexate (HDMTX: 3g/m2 infusion over 3h) at d8, followed by Vincristine, Daunorubicin (40mg/m2) d15, 22, 29; 8 injections of Asparaginase, 2 intrathecal injection MTX at d8 and d15 and prednisone for 4 weeks; two consolidation phases with HDMTX, Cyclophosphamide (CPM), Cytarabine and Asparaginase; one interphase with HDMTX and; an intensification phase similar to a phase II BFM study, a maintenance phase with Mercaptopurine/MTX including initially six intensified monthly pulse phases alternating either HDMTX/Asparaginase, or Cytarabine/prednisone. The total duration of treatment was 18 months for stage I, II and III and 24 months for stage IV. Cranial radiotherapy (18Gy) was only performed in pts with CNS disease. 66% were boys, median age was 10.5 y [1.9 – 17.2] and 88% had a mediastinal involvement. According to St Jude classification, 5 had a stage I or II (6%); 47 had a stage III (57%); 24 had a stage IV [ (63%), 18 bone marrow (BM) involvement, 4 CSF+ and 2 both]. 7 pts received corticosteroid before diagnosis and were classified as stage X and treated as stage IV. After induction phase and consolidation (d 65), the complete remission rate was 95%. 1 pt had a progressive disease and died and 2 pts in partial remission are alive after salvage treatment with local radiotherapy or intensification. Up to now, 8 pts relapsed between 3.7 months and 18 months (median=10.5 months) and 1 pt who developed a glioblastoma before relapsing at 69.2 months. All relapses were mediastinal, 3 were combined with BM and 1 with BM and CSF. The median of FU is 4 years. Five-year EFS is 87% [CI95%: 79–94] and OS is 89% [CI95%: 82–96]. In conclusion these results are as high as those of BFM experience. The intensified monthly pulse courses for 6 months did not seem decrease the relapses on therapy. Early intensification at d8 (with CPM and HDMTX) is feasible with a BFM regimen. Omission of prophylactic cranial irradiation while using a short duration (3 hours) of HDMTX infusion did not jeopardize the outcome. We suggest that our early intensification might be combined with a classic BFM regimen.
38
Patrick, Katharine, Rachel Wade, Nicholas Goulden, Clare Rowntree, Rachael Hough, Christopher D. Mitchell, and Ajay J. Vora. "Characteristics and Outcomes Of Patients With Down Syndrome Associated Acute Lymphoblastic Leukaemia Treated On UKALL 2003." Blood 122, no. 21 (November 15, 2013): 56. http://dx.doi.org/10.1182/blood.v122.21.56.56.
Анотація:
Abstract Children with Down Syndrome (DS) are at significantly increased risk of developing acute leukaemia, both AML and ALL. Whilst outcomes for AML are excellent, ALL associated with DS (DS-ALL) confers an inferior survival due to a combination of increased relapse risk and high treatment related mortality (TRM). We report the outcome for children and young adults with DS-ALL treated on a modern, intensive, minimal residual disease (MRD) directed protocol, UKALL2003. Treatment was not modified for DS-ALL patients at the start of the trial. NCI standard risk patients received a 3 drug induction with dexamethasone, vincristine and pegylated asparaginase. NCI high risk patients also received daunorubicin. MRD was measured at day 29 and MRD negative patients were randomised to standard or reduced intensity therapy. MRD high risk patients were randomised to standard therapy or an intensified regime consisting of augmented BFM consolidation, escalating Capizzi methotrexate and 2 delayed intensifications. Six years after the trial opened, an unacceptably high TRM in DS patients, (10 deaths out of 46 patients), prompted modifications to their treatment. DS patients were excluded from randomisations and, regardless of NCI risk, received a three drug induction with the addition of daunorubicin at day 15 for those with a slow morphological marrow response (>25% blasts). Patients with positive MRD at day 29 or those with a slow day 15 morphological response were treated with augmented therapy described above, in the absence of established significant comorbidity. All patients received only one delayed intensification and maintenance was shortened to 2 years for boys (standard duration 3 years).Strict supportive care measures during intensive phases of treatment were mandated. Of 3126 eligible patients in the trial, 85 (2.7%) had DS with median age 4 years (range 1-23 years). DS-ALL patients were more likely than non-DS-ALL patients to be male (68% vs 56%, p=0.03) and were almost exclusively B-cell precursor ALL (99 % vs 87%, p=0.001), but there were no significant differences by age, WBC or NCI risk. Nine of 80 DS-ALL patients from whom data on cytogenetic abnormalities was available had high hyperdiploidy (11% vs 30% in non-DS-ALL, p=0.0003), and 13 had an ETV6/RUNX1 fusion (16% vs 25%, p=0.06). With a median follow-up of 4 years 10 months, patients with DS-ALL had an inferior EFS compared to non-DS-ALL patients (65.3% (95% CI 54.5-76.1%) at 5 years vs. 87.8% (86.4-89.2%); OR=8.90 (95% CI: 4.53-17.48) p<0.00005). Of the 85 DS-ALL patients, 25 have died, 7 due to relapsed disease, 2 due to induction failure and death with active disease and 16 due to TRM during first line therapy. TRM deaths occurred throughout treatment (induction = 5, CR = 11) and were not confined to the most intensive phases. In all cases, deaths were due to infection, most commonly bacterial sepsis (75%) and viral pneumonitis (25%). The excess TRM was primarily responsible for the worse EFS for DS patients, as their risk of relapse (16.4% at 5 years ) was not significantly worse (p=0.1) than for non-DS patients (8.8%). In contrast to other recently reported studies, we report excess TRM as the main cause of treatment failure in DS-ALL, possibly due to the intensity of our treatment protocol which included dexamethasone and pegylated asparaginase for all patients. There have been fewer treatment related deaths in induction after introducing the treatment modifications in 2009 (4/46 vs 1/41) without an apparent increase in relapse risk. Improvements in outcome for this vulnerable group of patients will require such risk stratified treatment modifications, better supportive care and innovative agents that can replace the more intensive elements of current treatment schedules. Disclosures: No relevant conflicts of interest to declare.
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Burke, Patrick W., Ibrahim Aldoss, Matthew A. Lunning, Vassilios I. Avramis, Ann M. Mohrbacher, Vinod Pullarkat, Martin S. Tallman, and Dan Douer. "High-Grade Pegylated Asparaginase-Related Hepatotoxicity Occurrence In a Pediatric-Inspired Adult Acute Lymphoblastic Leukemia Regimen Does Not Necessarily Predict Recurrent Hepatotoxicity In Subsequent Cycles." Blood 122, no. 21 (November 15, 2013): 2671. http://dx.doi.org/10.1182/blood.v122.21.2671.2671.
Анотація:
Abstract Introduction Cure rates of pediatric acute lymphoblastic leukemia (ALL) have markedly improved to approximately 80%, while in adult ALL the rates remain 40-50%. Pediatric ALL regimens contain higher doses of non-myelosuppressive chemotherapy, e.g., vincristine, corticosteroids, and, particularly, higher cumulative doses of asparaginase. Asparaginase use in adults was previously limited due to toxicity concerns. However, several recent studies, using pediatric regimens in adults, contain higher cumulative doses of asparaginase and are showing promising preliminary results. In these studies it was also noted that the long-acting pegaspargase (PEG-ASN) was much more commonly associated with hepatotoxicity in adults than in children. Although hepatotoxicity appears to be the commonest adverse effect of PEG-ASN in adults, it has not been well defined. We report the frequency and characteristics of PEG-ASN-related high-grade hepatotoxicity after multiple doses in adults treated by a pediatric regimen. Methods Between July 2004 and July 2009, 51 adults aged 18 to 57 years were enrolled on a phase II trial with a pediatric ALL regimen that included six planned PEG-ASN doses. PEG-ASN-related toxicities were carefully monitored on a weekly basis after each dose and reported using NCI CTCAE v3.0 for 185 doses delivered. The PEG-ASN dosing schedule was: two doses in induction phases I and II, and four during post-induction cycles (ASH Abstract 1495, 2012). Each PEG-ASN dose was 2000 IU/m2/dose IV, given at intervals of four weeks or greater. Pegaspargase was not discontinued and subsequent doses were not reduced after hepatotoxicity. Results A total of 192 pegaspargase doses were delivered (3.8 doses/patient), with 23 patients receiving all six doses. Of the 28 patients who received fewer than six doses, only 10 (20%) discontinued due non-hepatic toxicity (pancreatitis, allergy, and DVT). Eight (16%) patients discontinued due to allogeneic HSCT while in CR1, while nine (18%) discontinued for other reasons (death post-induction, induction failure, and relapse). Grade 3/4 hyperbilirubinemia occurred in 16 patients (31%) and in 23 doses (12%); grade 3/4 transaminitis occurred in 33 patients (65%) and in 62 doses (34%). Patients with grade 3/4 hyperbilirubinemia tended to be older than those without hepatotoxicity (median age 39 vs 31 years), but all other baseline characteristics were similar. Results of different parameters related to high-grade liver toxicity are detailed in Table 1. Patients with grade 3/4 hyperbilirubinemia and transaminitis received a mean of 4.0 and 4.3 PEG-ASN doses, while the mean number of PEG-ASN doses causing hyperbilirubinemia and transaminitis was only 1.4 and 1.9 doses per patient, respectively. Those without hepatotoxicity received 2.8 PEG-ASN doses per patient. Induction I had the highest incidence (20% of doses delivered) of grade 3/4 hyperbilirubinemia. High-grade transaminitis was spread more evenly among cycles. Grade 3/4 hepatotoxicity was long, with a median duration of 34 days to return to grade 1 for bilirubin and 38 days to return to grade 2 for transaminitis. Of the 16 patients with grade 3/4 hyperbilirubinemia, five did not receive a subsequent PEG-ASN dose for other reasons; of the 11 other patients who received subsequent doses, five (45%) did not re-experience the same toxicity. Of the 33 patients with grade 3/4 transaminitis, eight did not receive a subsequent PEG-ASN dose due to other reasons; of the 25 other patients who received subsequent doses, 10 (40%) did not have this toxicity recur. Summary Our study shows in adults with ALL treated with multiple doses of PEG-ASN that: (1) high-grade hepatoxicity (grade 3/4 hyperbilirubinemia and transaminitis) is a common adverse effect of PEG-ASN; (2) recovery from hepatotoxicity is often long and can delay subsequent chemotherapy; (3) high-grade hepatotoxicity did not necessarily recur after subsequent doses and did not lead to PEG-ASN discontinuation; (4) the dose and schedule of other hepatically cleared or hepatotoxic drugs should be adjusted during periods of PEG-ASN-related hepatotoxicity. In conclusion, although PEG-ASN at this dose and interval is associated in adults with a high rate of hepatotoxicity, it is tolerable and can be given again despite earlier PEG-ASN-related hepatotoxicity. Disclosures: Douer: Sigma Tau Pharmaceuticals : Research Funding.
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Nguyen, Ryan Huu-Tuan, Lucia Notardonato, Alicia Hulbert, Apurva Mallisetty, Frank Weinberg, Israel Rubinstein, Irene Juson, et al. "LUNG-IST-127: A pilot phase II study of maintenance cabozantinib plus pembrolizumab for patients with metastatic squamous non-small cell lung cancer (sqNSCLC) with disease control following induction therapy." Journal of Clinical Oncology 41, no. 16_suppl (June 1, 2023): TPS9151. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.tps9151.
Анотація:
TPS9151 Background: First-line combination chemotherapy with pembrolizumab followed by maintenance pembrolizumab is the standard of care treatment for patients with metastatic sqNSCLC. This was established by the phase III KEYNOTE-407 trial, which demonstrated a median progression-free survival (PFS) of 6.4 months in the experimental arm. Despite these advances, there remains a need to continue to improve upon survival outcomes for these patients. Cabozantinib is a small-molecule inhibitor of multiple tyrosine kinsases including MET, VEGFRs, AXL, RET, and ROS, which are receptors involved in tumor cell-proliferation, angiogenesis, and immune cell regulation. Preclinical studies have demonstrated the ability of cabozantinib to modulate both adaptive and innate immune cells and to exhibit synergistic activity when used in combination with immune checkpoint inhibitors. We hypothesize that cabozantinib in combination with pembrolizumab in the maintenance phase of first-line treatment of metastatic sqNSCLC will prolong median PFS with a tolerable toxicity profile. Methods: LUNG-IST 127 is a pilot phase II, single-arm clinical trial of maintenance cabozantinib in combination with pembrolizumab for patients with metastatic sqNSCLC who achieved disease control following standard 1L induction therapy with chemotherapy and pembrolizumab. Thirty-six patients will be enrolled at 2 US sites to receive first-line induction therapy with carboplatin, nab-paclitaxel or paclitaxel, and pembrolizumab for four cycles. After induction therapy, those who have achieved disease control based on re-staging imaging will continue onto maintenance therapy with cabozantinib 40mg PO daily in combination with pembrolizumab 200mg IV every 3 weeks. The primary endpoint is PFS estimated by Kaplan-Meier methods with associated 95% confidence intervals. Based on an exploratory power analysis using an elevated one-sided alpha level of 0.40, we hypothesize that the proposed therapy will prolong median PFS from 6.4 to 9 months. Key secondary endpoints include overall survival (OS), overall response rate (ORR), and characterizing the safety and tolerability of cabozantinib in combination with pembrolizumab. Quality of life will also be measured with the EORTC QLQ-C30. Correlative endpoints include characterizing cfDNA from biofluids and assessing the change in circulating immune cells in different phases of treatment in association with PFS and OS. This trial would be the first to address whether there is clinical benefit in utilizing combination cabozantinib and pembrolizumab in the maintenance phase of treatment in metastatic sqNSCLC. Clinical trial information: NCT05613413 .
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ADNAN, Moh Rosyadi, Dwi Mai A. I. BUQORI, Kyung Min KIM, Muhammad Noval KHULUQ, and Muhammad UBAIDILLAH. "Response of Morphogenesis and Cell Proliferation to Allelopatic Compounds on Rice Germplasm." Eurasia Proceedings of Health, Environment and Life Sciences 8 (January 4, 2023): 14–27. http://dx.doi.org/10.55549/ephels.48.
Анотація:
Allelopathic compounds are chemical substances produced by weeds, including Imperata cylindrica, that can inhibit the absorption of nutrients and cell growth of neighboring plants. Tissue culture technique can be used to determine the effect of media composition on morphogenesis and cell proliferation, as indicated by related genes. Through the process of somatic embryogenesis, cells regenerate into whole plants via several phases initiated by gene expression. Genes are the signal that connects environmental cues and plant cells. The objective of this study was to determine the effect of allelopathic compounds from Imperata cylindrica root extract on the morphogenesis and cell proliferation of indigenous Indonesian rice plant. The used callus was derived from the seeds of Bondoyudo, Caok, Ciliwung and Situbagendit rice varieties. The results of callus induction were selected and transferred to regeneration media that had been treated with I. cylindrica roots extract of 2.5 g/L and 5 g/L. The development of callus was monitored weekly for six weeks. As for the molecular analysis, four-week-old callus was utilized. The results demonstrated that the root extract of Imperata cylindrica had a specific effect on the morphogenesis and proliferation of rice cells depending on concentration and target plant. At a molecular level, the expression of the OsBBM, OsLEA, OsLEC1, OsSERK, and OsWOX4 genes was affected differently by the administration of allelopathic compounds at a concentration of 5 g/L on a molecular level.
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Rozen, Laurence, Denis F. Noubouossie, Laurence Dedeken, Sophie Huybrechts, Phu-Quoc Le, Alina Ferster, and Anne Demulder. "Thrombin Generation Test During Asparaginase Treatment In Children With Acute Lymphoblastic Leukemia." Blood 122, no. 21 (November 15, 2013): 2367. http://dx.doi.org/10.1182/blood.v122.21.2367.2367.
Анотація:
Abstract Asparaginase (Aase) and corticosteroid (CS) used to treat acute lymphoblastic leukemia (ALL) in children during the Induction and Late Intensification phases have adverse effects on coagulation and increase the incidence of thrombotic events. Aase and CS reduce both pro- and antithrombotic factors and most studies have evaluated the individual components of the coagulation system to infer the prothrombotic profile. However, global haemostatic potential of these children and its changes during treatment are poorly reported. We aimed to characterize the global haemostatic phenotype of ALL patients during native Aase therapy, using a global haemostatic assay, the Calibrated Automated Thrombogram® (CAT) method of thrombin generation (TG) in B lineage ALL children treated according to the latest CLG-EORTC first-line protocol (a BFM derived protocol). CAT method was performed on platelets-poor plasma (PPP) at diagnosis (day 1), before each Aase infusion (8 during Induction and 4 during Late Intensification), and at distance of Aase infusion (during and after Interval Therapy and at start of Maintenance). TG was triggered using 1pM tissue factor (TF) and 4µM phospholipids (PL), with and without addition of thrombomodulin (TM). Endogenous Thrombin Potential (ETP) and Peak were monitored and the interquartile range was compared to the [2,5 – 97,5] percentile range of normal controls (NC) of the same range of age (n=28). Protein C activity (PC), free Protein S (PS), antithrombin (AT) and fibrinogen levels were also measured. Results Thirty six children were included (20 boys and 16 girls). Their median age at diagnosis was 3.7 years (range 1-14). Twenty had pre-B ALL and 16 common ALL. Elevated ETP and Peak of TG in ALL patients above the 97,5 percentile of NC were noted at diagnosis and persisted during all the Induction phase. During Interval Therapy and later at start of Maintenance, ETP and Peak returned to values below 97.5 percentile of NC. During Late Intensification, ETP and Peak levels increased above the 97.5 percentile of NC. At all time points studied the variation of ETP and Peak levels were similar in the presence and absence of TM. PC, PS, AT and fibrinogen levels decreased during Induction phase with median PS level remaining within the 2.5-97.5 percentile of NC and median AT and PC levels reaching a value lower than the 2.5 percentile of NC at the time of the 7th and 8th Aase infusion respectively (day 32 and 35). Fibrinogen levels were below the 2.5 percentile of NC during Induction from day 15 to day 29. Among the 36 analyzed patients, 2 experienced 3 symptomatic thromboses. One sub-clavian thrombosis occurred during Induction on day 22 and 1 jugular vein thrombosis occurred in a second child after completion of Induction on day 50 (13 days after the 8thAase infusion). These 2 events were concurrent with a central venous catheter infection. The second patient also developed during Late Intensification a cerebral thrombosis in the longitudinal sinus. Concomitant to these three events, ETP and Peak values of these patients were above the P75 value of ALL patients sampled at the same time points compatible with a marked prothrombotic profile and a higher risk of thrombosis. This study suggests that TG is a promising global assay to evaluate the hypercoagulable state in ALL children under treatment. TG reveals an increased thrombin potential which is present early at diagnosis, persists during Induction and reappears during Late Intensification. This observation is consistent with the high incidence of thrombotic events previously described during Induction and until 10 days after the last Aase infusion. TG profiles observed in patients who experienced thrombotic events suggest that this assay could be used as a predictive tool since their TG parameters were above P75 value of the ALL children tested. Further investigations are needed to address this issue. Disclosures: No relevant conflicts of interest to declare.
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Mendiola, Vincent Louie, Catherine Ly, Thuy Bui, Jennifer Wang, Jack Rodman, Maria E. Vergara-Lluri, Karrune Woan, et al. "An Update on Outcomes Using the USC ALL Frontline Regimen (based on CCG-1882) after Further Modification of Protocol in the Era of Novel Agents in Ph-Negative ALL Patients; A Retrospective Study." Blood 138, Supplement 1 (November 5, 2021): 3362. http://dx.doi.org/10.1182/blood-2021-147124.
Анотація:
Abstract INTRODUCTION: The use of pediatric inspired regimens in adolescent young adults and adults has improved outcomes in acute lymphoblastic leukemia (ALL). CALGB 10403 was prospectively tested in patients 17-39 years, showing a 3-year event free survival of 59%. In 2007, our institution reported outcomes after incorporating peg-asparaginase (PEG) dosed at 2000mg/m 2 in induction for patients aged 17- 55 years. This regimen was well tolerated and resulted in a complete remission (CR) rate of 96%. In 2014, we reported experience with the use of multiple doses of PEG (CCG-1882) for newly diagnosed ALL adult patients, with a 7-year overall survival (OS) of 51%. Since our last report, the USC ALL regimen consisting of 2 induction phases, has been further modified with a goal of maintaining good outcomes, and improving compliance and toxicities. Fractionated doses of cytarabine were changed to a single dose, the methotrexate dose of 1g/m 2 (2.5 g/m 2 if T-cell) given D1,15 of intensification phases was changed to 3g/m 2 (B and T cell) given in single doses, and consolidation was increased to six cycles allowing for PEG holidays (Table 1). Moreover, the approval and incorporation of novel agents such as blinatumomab and inotuzumab also changed outcomes in ALL. Therefore, this study reports an update of outcomes since further modification of the USC ALL pediatric-based regimen in the era of novel agents. METHODS: This is a retrospective review which included adults aged >18 with newly diagnosed Philadelphia negative ALL between 2016 and 2020 treated at USC/Norris Cancer Center and Los Angeles County Hospital (LAC). Primary objectives were over-all survival (OS), event-free survival (EFS), disease-free survival (DFS) at 3 years, and secondary outcomes were complete remission/complete remission with incomplete recovery (CR/CRi) rates and minimal residual disease (MRD) by flow cytometry. OS, DFS, EFS were reported through Kaplan Meier curves and Log-rank tests. Two-sided p value ≤0.05 was significant. RESULTS: 121 patients with Ph-negative ALL were identified (49.6% Ph-negative B-ALL, 24% Ph-like B-ALL, 0.8% B cell lymphoblastic leukemia (LBL), 9.1% T cell ALL, 4.1% T cell LBL, 4.1% early T-cell, 5.8% mixed phenotype acute leukemia (MPAL). Median age at diagnosis was 38.5 years and maximum age of patient to receive pegasparagase during induction 1 was 63 years. 71.9% Hispanic, 15.7% white, 9.9% Asian, 2.5% African American. 57.9% males, 42.1% females. 3.4% were favorable, 4.2% intermediate, 54.6% unfavorable and 37.8% unknown by karyotypic risk stratification. Median BMI was 28.9 kg/m 2.54.6% had hepatic steatosis either on history or imaging and 5.1% had CNS disease pre-induction. Post-induction 1, 81.4% of patients achieved CR/CRi and 50% MRD negative. Post induction 2, 82.2% achieved CR/CRi, 67.7% MRD flow negative. Post-consolidation 1, 90.9% were MRD flow negative. 33.1% subsequently received blinatumomab for MRD positive disease, 5% given inotuzumab for relapsed disease, 32.2% underwent allogenic hematopoietic stem cell transplant (allo-HSCT). Median number of pegasparagase doses received during treatment was 2, rate of relapse and mortality was 27.3% and 13% respectively. Median OS and DFS were not reached but median EFS was 35 months. 3-year OS was 85.3%, when stratified according to MRD post induction 2; 3-year OS was 91.7% for MRD positive patients and 91.2% for MRD negative patients (p=0.55). 3-year DFS was 83.2%; 88.2% for MRD positive patients and 97.4% for MRD negative patients (p=0.22). 3-year EFS was 47.3%; 51.3% for MRD positive patients and 50.6% for MRD negative patients (p=0.49) (Tables 2-3). Use of pegasparagase resulted in grade 3/4 toxicities including hypersensitivity (4.1%), transaminitis (21.5%), pancreatitis (5.4%), hypertriglyceridemia (49.5%), hypofibrinogenemia (45.5%), hyperbilirubinemia (21.5%) and thrombosis (16.5%). CONCLUSIONS: Pediatric-based modified USC ALL induction regimen led to a high 3-year OS (85.3%), DFS (83.2%) and EFS (47.3%) with predictable toxicity and compares favorably with original USC ALL regimen, CALGB 10407, GRAALL 2005 and USC/MSKCC regimen. Interestingly, MRD positivity after induction 2 did not adversely affect OS, DFS or EFS, which is likely due to incorporation of blinatumomab and inotuzumab. These agents could have allowed for deeper remissions allowing Ph-negative patients with residual disease to receive allo-HSCT. Figure 1 Figure 1. Disclosures Chaudhary: Oncotartis: Consultancy; Pancella: Consultancy; Moderna: Current equity holder in publicly-traded company; Celldex: Current equity holder in publicly-traded company; TCR2: Current equity holder in publicly-traded company; Allogene: Current equity holder in publicly-traded company; Athelas: Consultancy, Current holder of stock options in a privately-held company; Angeles Therapeutics: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Founder, Patents & Royalties: Cell therapy . Douer: Servier: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Adaptive: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Speakers Bureau; Jazz: Consultancy. Yaghmour: Novartis: Consultancy, Speakers Bureau; BMS: Speakers Bureau; Alexion: Speakers Bureau; Astellas: Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Jazz: Speakers Bureau; Agios: Consultancy, Speakers Bureau.
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Mehmood, Abid, Sadia Abid, Pavla Hejcmanová, Muhammad Arslan Asadi, Bilal Kabeer, Muhammad Jawad Jilani, Sadaf Bilal, and Muhammad Waseem Ashraf. "Comparison of physiological responses of Arabian striped hyaena (Hyaena hyaena sultana) to effective immobilisations with ketamine-medetomidine and ketamine-xylazine in (semi-) captive conditions." PeerJ 7 (July 26, 2019): e7326. http://dx.doi.org/10.7717/peerj.7326.
Анотація:
Chemical immobilisation is an integral component for the conservation of wild animals and can be stressful if proper protocols are not administered. References on the immobilisation of Arabian striped hyaena (Hyaena hyaena sultana) are scarce. The current study was designed to evaluate the physiological and clinical responses of Arabian striped hyaena, immobilised with ketamine-medetomidine (KM) and ketamine-xylazine (KX); and to compare immobilisation effectiveness of the two combinations in a cross-sectional clinical study. A total of 15 (six males, nine females) (semi-) captive and adult Arabian striped hyaena with an average weight of 31.39 ± 0.36 kg were immobilised 50 times for annual vaccination and translocation purposes from January 2014 till March 2018 on Sir Bani Yas Island, United Arab Emirates. A total of 34 immobilisations were executed with (Mean ± SE) 2.27 ± 0.044 mg/kg ketamine and 0.04 ± 0.001 mg/kg medetomidine; while 16 with 4.95 ± 0.115 mg/kg ketamine and 0.99 ± 0.023 mg/kg xylazine. The drugs were remotely delivered intramuscular. The evaluation of physiological and clinical parameters included monitoring of vital signs through pulse oximetry, blood gas analysis of arterial blood through Istat blood gas analyser, and blood biochemistry and haematology. The quality of induction, anaesthesia and recovery was also assessed. Atipamezole (0.21 ± 0.003 mg/kg) was used to antagonise the effects of KM and 0.09 ± 0.003 mg/kg atipamezole or by 0.23 ± 0.006 mg/kg yohimbine for KX. Data were analysed using the general linear model and inferential statistics. KM was more effective in induction (scores; KM = 1.41 ± 0.10; KX = 1.31 ± 0.12), anaesthesia (KM = 1.00 ± 0.00; KX = 2.0 ± 0.0) and recovery (KM = 1.76 ± 0.15; KX = 2.69 ± 0.12) phases as compared to KX. There was a significant difference (P < 0.05) amongst the two combinations for anaesthesia time (KM = 59.5 ± 2.41; KX = 49.25 ± 1.31 min.), time to stand after reversal (KM = 4.91 ± 0.60; KX = 10.38 ± 1.48 min.) and full loss of the signs of anaesthetics (KM = 12.32 ± 1.37; KX = 21.25 ± 2.16 min.) along with rectal temperature (KM = 37.58 ± 0.29; KX = 36.00 ± 0.68 °C), pulse rate (KM = 50.46 ± 1.90; KX = 61.14 ± 2.79 beats/min), respiration rate (KM = 29.44 ± 0.99; KX = 23.80 ± 1.57 breaths/min.) and partial pressure of oxygen (KM = 89.59 ± 1.34; KX = 82.06 ± 3.92%). The blood oxygen saturation by oximeter indicated hypoxaemia in KX (82.06 ± 3.92), supported by the data from blood gas analyser. KM combination was more suitable for the immobilisation of Arabian striped hyaena, providing a better quality of induction, anaesthesia and recovery compared to KX. However, we strongly suggest further investigation to see the effects of oxygen supplementation for the compensation of hypoxaemia.
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Vrooman, Lynda M., Yael Flamand, Victoria Koch, Melissa A. Burns, Sarah M. Cronholm, Sarah K. Hunt, Peter D. Cole, et al. "Pegaspargase Re-Challenge after Grade 2 Hypersensitivity Reaction in Childhood Acute Lymphoblastic Leukemia: Results from DFCI 16-001." Blood 136, Supplement 1 (November 5, 2020): 30–31. http://dx.doi.org/10.1182/blood-2020-138840.
Анотація:
Introduction: Hypersensitivity reactions with asparaginase occur frequently in pediatric patients (pts) with acute lymphoblastic leukemia (ALL). The standard approach for pts with reaction to E.coli-derived asparaginase is to switch to Erwinia asparaginase, given concern that clinical reactions reflect presence of neutralizing antibodies; however, Erwinia requires more frequent dosing and is often unavailable. Therapeutic drug monitoring allows for discrimination between pts with pegaspargase hypersensitivity who have sub-therapeutic asparaginase activity and those still able to derive therapeutic benefit from pegaspargase. We prospectively piloted re-challenging pts with pegaspargase after initial Grade 2 hypersensitivity to this agent, with premedication at re-challenge and assessment of serum asparaginase activity (SAA). Methods: Pts aged 1 to < 22 years with newly diagnosed ALL were eligible for DFCI 16-001. Pts received 1 dose of intravenous pegaspargase during Induction, and every 2 weeks for 15 total doses in Post-Induction phases, without routine premedication. Pts were monitored during/after pegaspargase for allergy, with CTCAE version 4.0 event grading. Those with ≥Grade 3 allergy discontinued pegaspargase and were switched to Erwinia. Those with Grade 2 allergic reaction were eligible for pegaspargase re-challenge with pre-medication (acetaminophen, diphenhydramine, and hydrocortisone, or per institutional standard) and slower infusion rate. If < 50% of the intended dose had been administered when reaction occurred, re-challenge was within 1-7 days of initial reaction. If ≥ 50% of the intended dose had been given, re-challenge was at next planned pegaspargase dose. SAA was measured 1-hour, 7-days, and 14-days after the re-challenge infusion (if dose completed). If 1-hour or 7-day level ≥ 0.1 IU/mL, and 14-day level ≥ 0.025 IU/mL, SAA was considered adequate, and the pt continued to receive pegaspargase with premedication. Pts with an inadequate SAA level, or with new ≥ Grade 2 allergic reaction with the re-challenge dose were considered to have failed re-challenge and were changed to Erwinia (or enrolled on a clinical trial of recombinant crisantaspase, an alternative Erwinia preparation). Results: Between 3/2017- 7/2020, 317 eligible pts enrolled. Overall, 81 of 299 (27%) total evaluable pts experienced a first allergic reaction to pegaspargase, 68 pts with Grade 2 reaction, 13 with Grade ≥3. During Induction, 17 of 299 (6%) evaluable pts had allergic reaction to pegaspargase; all Grade 2. Of the 17 Grade 2 reactions, 13 pts (76%) underwent re-challenge in Induction, 9 (69%) re-challenges successful and 4 failed. Post-Induction, 64 of 241 evaluable pts (27%) had a first allergic reaction; 51 Grade 2 and 13 Grade ≥3. Thirty-six of 51 (71%) pts with Grade 2 allergy during Post-Induction underwent re-challenge, as did 1 additional pt with allergy during Induction who was re-challenged with first Post-Induction pegaspargase dose (per protocol guideline, due to receiving ≥50% of Induction dose). Among these re-challenges, 16 were successful, 21 failed. Overall, 25 of 50 (50%) pts who were re-challenged after Grade 2 reaction had a successful challenge and were able to continue pegaspargase. Among the 25 pts with failed re-challenge, 6 pts (24%) had inadequate SAA alone as cause of failure, 17 pts (68%) had an allergic reaction with the re-challenge dose, and 2 (8%) additional patients had both allergic reaction and documented inadequate SAA. Three pts who were successfully re-challenged had a subsequent allergic reaction to pegaspargase. Among the 22 pts who experienced another allergic reaction with pegaspargase (at re-challenge or subsequent dose), 19 pts (86%) experienced Grade 2, and 3 pts experienced Grade 3 reaction. Conclusion: Fifty percent of pts with a Grade 2 reaction to pegaspargase were able to tolerate and achieve adequate SAA when re-challenged with premedication. For those who did react with or after re-challenge, reactions were not more severe. The re-challenge approach limits premedication exposure only to a minority of pts with a history of prior reaction and substantially decreases the number of pts needing to switch to Erwinia asparaginase, which can be challenging to deliver due to administration schedule and drug shortage. Disclosures Place: Novartis: Consultancy, Other: Institutional Research Funding; AbbVie: Consultancy. Silverman:Takeda: Other: advisory board; Servier: Other: advisory board; Syndax: Other: advisory board.
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Takahashi, Hiroyuki, Tomoyuki Watanabe, Akitoshi Kinoshita, Yuki Yuza, Hiroshi Moritake, Kiminori Terui, Shotaro Iwamoto, et al. "High Event-Free Survival Rate with Minimum-Dose-Anthracycline Treatment in Childhood Acute Promyelocytic Leukemia: A Nationwide Prospective Study By the Japanese Pediatric Leukemia / Lymphoma Study Group (JPLSG)." Blood 124, no. 21 (December 6, 2014): 956. http://dx.doi.org/10.1182/blood.v124.21.956.956.
Анотація:
Abstract Introduction: Anthracyclines (Atc) are the key drugs in the treatment of acute promyelocytic leukemia (APL) combined with all-trans retinoic acid (ATRA), however, dose-dependent risk of long-term cardiac toxicity is sometimes problematic especially in pediatric patients. To evaluate efficacy of the treatment with reduced cumulative doses of Atc in childhood APL, we conducted a nationwide non-randomized prospective study, AML-P05, in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG). Patients & Methods: Between April 2006 and March 2011, forty-six children with newly diagnosed APL were enrolled in this study. All patients received at least 3-day precedence of ATRA monotherapy (45mg/m2/d for 35 days in total), followed by chemotherapeutic agents consisted of cytarabine (200mg/m2/d for 7 days) and daunorubicin (DNR, 45mg/m2/d for 3 days) as the first induction therapy. The second induction therapy and subsequent 3 courses of consolidation therapy consisted of ATRA, either high- or intermediate-dose of cytarabine, triple intrathecal injection, and single dose of Atc; 10mg/m2 of mitoxantrone (MIT) in the first 2 courses and 45mg/m2 of pirarubicin (THP) in the last 2 courses. Finally, patients received one-year maintenance therapy with ATRA for 15 days every 3 months. Results: Among the 46 patients registered in this study, 3 were excluded because of PML/RARA negativity, and the remaining 43 patients including 2 with molecular variants were evaluated. The median age at diagnosis was 9 years (range, 11 months to 15 years old). The median follow up period was 4.47 years (0.00-7.45 years). FLT3-ITD was positive in 6 out of 40 patients examined. Two patients died during induction therapies; one of coagulopathy in first course and the other of infection in second course. Two patients developed differentiation syndrome but resolved with temporary cessation of ATRA and supportive therapies. Three patients did not achieve complete remission (CR) after 2 courses of induction therapy, and overall CR rate was 85.7% (36/42, 95%CI: 71.5-94.6%). Neither cardiac adverse events nor treatment-related death were observed during consolidation and maintenance therapies. Three patients exhibited relapse during or after maintenance therapy, and another one developed secondary acute myeloid leukemia. Consequently, the 3-year event-free (EFS) and overall survival rate were 83.6% (95%CI: 68.6-91.8%) and 90.7% (95%CI: 77.1-96.4%), respectively. Age less than 4 years old at diagnosis and non-M1 marrow after first induction therapy were associated with lower EFS. High WBC count (>10,000/μL), low platelet count (<40,000/μL), FLT3-ITD positivity, and additional chromosomal abnormality did not influence the risk of events. Conclusions: According to the JPLSG criteria of Atc equivalents, cumulative Atc dose in this study was converted to 246mg/m2 of doxorubicin (for 1:0.83 for DNR, 1:4 for MIT, and 1:0.6 for THP). The dose was much lower than that in recent US or European protocols, especially in those designed primarily for adult APL patients where more than 600mg/m2 of Atc were used. Comparing with these studies, we have achieved equivalent good results with minimum does of Atc. Therefore, single administration of Atc in each consolidation phases seems sufficient in the treatment of childhood APL. This trial is registered with UMIN Clinical Trials Registry (UMIN-CTR, URL: http://www.umin.ac.jp/ctr/index.htm), number UMIN000000645 Disclosures No relevant conflicts of interest to declare.
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Blomberg, Ben A., Hendrik W. Van Deventer, Stuart Gold, Katarzyna Joanna Jamieson, Joshua F. Zeidner, Benyam Muluneh, Dominic Moore, and Matthew C. Foster. "A Single-Center Retrospective Analysis of a Pediatric Salvage Chemotherapy Regimen for Adults with Relapsed/Refractory Acute Lymphoblastic Leukemia." Blood 126, no. 23 (December 3, 2015): 4919. http://dx.doi.org/10.1182/blood.v126.23.4919.4919.
Анотація:
Abstract Background: Relapsed or refractory acute lymphoblastic leukemia (ALL) remains challenging to treat with an extremely poor prognosis. Salvage chemotherapy regimens can achieve complete remission (CR) rates of 30-50%, but CRs are not durable without hematopoietic stem cell transplant (HSCT). Outcomes in untreated adolescents and young adults have improved with the use of pediatric chemotherapy regimens, but data on the use of pediatric chemotherapy regimens in relapsed/refractory adult ALL is lacking. We chose to retrospectively examine the outcomes of adult patients with relapsed ALL at our institution treated with the CCG-1941 pediatric salvage protocol (Gaynon PS, et al. J Clin Oncol 2006). Methods: We conducted a single-center retrospective cohort study of patients aged 18 and older with relapsed/refractory ALL who were treated with the CCG-1941 protocol. Patients received induction with vincristine, dexamethasone, ifosfamide, etoposide, PEG-asparaginase, and methotrexate, as well as intrathecal methotrexate, cytarabine, and hydrocortisone prophylaxis, followed by intensification and continuation phases. This regimen was offered to relapsed/refractory patients who, in the judgement of treating physician, were likely to tolerate multiagent chemotherapy. All adult patients who received this regimen between 2006 and 2015 were included in the analysis. Outcomes of interest were: the CR rate, duration of remission (DOR), toxicity, 30-day mortality, and the rate of patients undergoing HSCT. Results: Between January 2006 and April 2015, 15 patients aged 20-54 (median 31) with first relapse (n=12) or refractory (n=3) ALL were treated with the CCG-1941 regimen. Baseline patient characteristics are described in the Table 1. Seven patients (47%) had alterations to the induction protocol. The majority of these modifications were reduction or omission of PEG-asparaginase or vincristine. All patients experienced infectious complications, most commonly neutropenic fever (n= 12, 80%, 95% CI 52-96). There was one death due to infection, which occurred during an intensification phase. Two patients had grade 3 pancreatitis and two patients had hemorrhage (one grade 2, and one grade 5). 30-day mortality was 7% (95% CI 0-32) due to one fatal intracranial hemorrhage. Median length of hospitalization for induction was 28 days (range 10-61). Twelve patients (80%, 95% CI 52-96) achieved CR, and six of these patients received 1-2 cycles of intensification or continuation. Among the remaining 6 CR patients, one proceeded immediately to HSCT, two received other consolidation, two had early relapse, and one was lost to follow up. Six patients proceeded directly to HSCT, and one more underwent HSCT after receiving subsequent therapies for relapsed disease. The DOR was 81% at 6 months, 54% at 12 months, 36% at 18+ months and 18% at 24 months. One patient has been followed for 63 months and has not recurred. Median follow-up for survivors was 16 months (range 3.6-63). Conclusions: The CCG-1941 regimen appears to be tolerable and efficacious in adult patients with relapsed/refractory ALL. This regimen has been previously reported only in children. Despite the regimen's toxicities, a substantial proportion of patients underwent subsequent stem cell transplantation. Such salvage therapies remain important options for patients with T-ALL and for those B-ALL patients who are not candidates for, or who have failed phenotype-specific immunotherapies. Further prospective, multicenter study is warranted for use of pediatric salvage regimens in the adult patient population. Disclosures Foster: Celgene: Research Funding.
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Панин, П. В., Е. А. Лукина, И. А. Богачев, П. Н. Медведев, and С. А. Наприенко. "ADDITIVE SYNTHESIS OF A TiAl-alloy Ti–Al–V–Nb–Cr–Gd SYSTEM BY SELECTIVE ELECTRON BEAM MELTING." Metallurg, no. 3 (September 14, 2023): 55–65. http://dx.doi.org/10.52351/00260827_2023_03_55.
Анотація:
Исследованы технологические свойства, химический и фазовый составы металлопорошковой композиции (фракции 40–100 мкм) из нового шестикомпонентного интерметаллидного бета-затвердевающего TiAl-сплава Ti–44,5Al–2V–1Nb–2Cr–0,1Gd, ат. % (Ti–31,0Al–2,5V–2,5Nb–2,5Cr–0,4Gd, масс. %), полученной методом бестигельной индукционной плавки и газовой атомизации литого электрода, и предназначенной для аддитивного синтеза деталей по технологии селективного электронно-лучевого сплавления (СЭЛС). Показано, что химический состав МПК по основным элементам соответствует химическому составу электрода, а фазовый состав МПК соответствует быстрозакристаллизованному метастабильному состоянию (γ+α+β). Достигнуты высокие показатели качества по текучести и сферичности МПК. Установлено, что содержание Al в синтезированном состоянии по сравнению с исходным электродом уменьшается на 1,1–1,3 ат. % (1,0–1,2 масс. %) вследствие испарения. Микроструктура синтезированных заготовок представлена внутризеренными пластинчатыми (γ+α2)-колониями и фазами γ и β0/B2 по границам зерна. Выявлено неравномерное распределение Ti и Al по сечению вдоль направления построения (Z), приводящее к неоднородному распределению фаз и размера зерен. Областей с дуплексной или крупно-глобулярной γ-фазой, характерных для синтезированного TiAl-сплава 2-го поколения Ti-4822, не выявлено. Technological properties, chemical composition, and structure have been investigated for metal powder composition (MPC fraction 40–100 μm) of a new six-component intermetallic beta-solidifying TiAl-alloy Ti–44.5Al–2V–1Nb–2Cr–0.1Gd, at. % (Ti–31.0Al–2.5V–2.5Nb–2.5Cr–0.4Gd, wt. %) produced by crucible-free induction melting of cast electrode and inert gas atomization technique, and targeted for additive manufacturing of dense parts by selective electron beam melting (SEBM) technology. It is shown that the chemical composition of MPC for the main elements corresponds to that of the electrode, and the phase composition of MPC corresponds to a rapidly solidified metastable state (γ+α+β). High quality indicators have been achieved for raw MPC in terms of flowability and sphericity. A reduction of Al content by 1.1–1.3 at. % (1.0–1.2 wt. %) compared to the starting electrode has been detected after SEBM due to evaporation. The microstructure of as-SEBM-built testpieces exhibited intragranular (γ+α2) lamellar colonies and some γ and β0/B2 phases at grain boundaries. An inhomogeneity of Ti and Al cross-sectional contents has been revealed along the building direction (Z), resulting in a non-uniform distribution of phases and grain size. No areas were identified with duplex or coarse-grained γ phase which are characteristic for the 2nd generation electron beam melted TiAl-alloy Ti-4822.
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Parra Izquierdo, L. V., J. Frías-Ordoñez, J. R. Márquez, F. Juliao-Baños, P. Galindo, C. Cuadros, C. Rojas, et al. "P735 Real-life experience with the use of Tofacitinib in Colombian patients with moderate to severe Ulcerative Colitis: a descriptive study." Journal of Crohn's and Colitis 17, Supplement_1 (January 30, 2023): i863—i866. http://dx.doi.org/10.1093/ecco-jcc/jjac190.0865.
Анотація:
Abstract Background In Latin America the experience in clinical practice with tofacitinib for moderate to severe Ulcerative Colitis (UC), in terms of both effectiveness and safety, is still limited. In Colombia, the incidence of UC as well as the availability of these new therapeutic options has been increasing, also, patients are frequently more refractory to treatments with higher rates of hospitalizations and surgeries. The aim of this study is to describe the real-life experience in Colombian patients with UC treated with Tofacitinib. Methods descriptive observational study, patients with moderate-severe UC as defined by the American College of Gastroenterology Ulcerative Colitis Activity Index (ACG score) treated with tofacitinib in induction phase (10mg every 12 hours) and maintenance (5mg every 12 hours), in different reference centers nationwide. Therapeutic response was evaluated in endoscopic (Mayo score), paraclinical (CRP, ESR, fecal calprotectin, hemoglobin) and clinical (absence of abdominal pain, diarrhea and rectorrhagia) terms. Additionally, the frequency of adverse events, steroid use and extraintestinal manifestations were measured. Results 51 patients, 55% women, the average age was 37,14 years (range14-72). All patients had moderate to severe UC; 73% patients with pancolitis, and 21,6% with left colitis. The mean age at UC diagnosis was 29,77 (SD17,8) years (range 12.77-66,4). And the mean time between disease onset and tofacitininb initiation was 7,33 (SD17,1) years (range 0.001-22.72). 42/51(82,4%) patients had previously failed tumor necrosis factor inhibitors and 15/51(29,4%) had failed alpha4 beta7 integrin inhibitor (Vedolizumab). Six patients were naïve to any biologic drug. Ten patients had extraintestinal manifestations. During the induction phase, 68,6% achieved clinical remission, 58,8% endoscopic remission, and 60,8% paraclinical remission. During maintenance phases, information was obtained from 18 patients during the first 6 months, 16 of whom reported clinical, paraclinical and endoscopic remission, while information was obtained from 7 patients at 12 months, 5 of whom showed clinical remission, and 6/7 endoscopic and paraclinical remission. Four patients reported adverse events No thromboembolic or cardiovascular events were reported. Conclusion Tofacitinib is an effective and safe therapeutic alternative in the management of moderate-severe UC in our population. It is safe in patients with previous use of anti-TNF and anti-integrin, without presenting thrombotic or cardiovascular events. Also, it is a promising alternative in the bio-naïve patient. Its use in pediatric patients is off-label, the patients included presented clinical and paraclinical remission.
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Khusnutdinova, Elmira, Anastasiya Petrova, Zulfia Zileeva, Ulyana Kuzmina, Liana Zainullina, Yulia Vakhitova, Denis Babkov, and Oxana Kazakova. "Novel A-Ring Chalcone Derivatives of Oleanolic and Ursolic Amides with Anti-Proliferative Effect Mediated through ROS-Triggered Apoptosis." International Journal of Molecular Sciences 22, no. 18 (September 10, 2021): 9796. http://dx.doi.org/10.3390/ijms22189796.
Анотація:
A series of A-ring modified oleanolic and ursolic acid derivatives including C28 amides (3-oxo-C2-nicotinoylidene/furfurylidene, 3β-hydroxy-C2-nicotinoylidene, 3β-nicotinoyloxy-, 2-cyano-3,4-seco-4(23)-ene, indolo-, lactame and azepane) were synthesized and screened for their cytotoxic activity against the NCI-60 cancer cell line panel. The results of the first assay of thirty-two tested compounds showed that eleven derivatives exhibited cytotoxicity against cancer cells, and six of them were selected for complete dose–response studies. A systematic study of local SARs has been carried out by comparative analysis of potency distributions and similarity relationships among the synthesized compounds using network-like similarity graphs. Among the oleanane type triterpenoids, C2-[4-pyridinylidene]-oleanonic C28-morpholinyl amide exhibited sub-micromolar potencies against 15 different tumor cell lines and revealed particular selectivity for non-small cell lung cancer (HOP-92) with a GI50 value of 0.0347 μM. On the other hand, superior results were observed for C2-[3-pyridinylidene]-ursonic N-methyl-piperazinyl amide 29, which exhibited a broad-spectrum inhibition activity with GI50 < 1 μM against 33 tumor cell lines and <2 μM against all 60 cell lines. This compound has been further evaluated for cell cycle analysis to decipher the mechanism of action. The data indicate that compound 29 could exhibit both cytostatic and cytotoxic activity, depending on the cell line evaluated. The cytostatic activity appears to be determined by induction of the cell cycle arrest at the S (MCF-7, SH-SY5Y cells) or G0/G1 phases (A549 cells), whereas cytotoxicity of the compound against normal cells is nonspecific and arises from apoptosis without significant alterations in cell cycle distribution (HEK293 cells). Our results suggest that the antiproliferative effect of compound 29 is mediated through ROS-triggered apoptosis that involves mitochondrial membrane potential depolarization and caspase activation.