scholarly journals Differential response to cytotoxic therapy explains treatment dynamics of AML patients: insights from a mathematical modelling approach

2020 ◽  
Author(s):  
H. Hoffmann ◽  
C. Thiede ◽  
I. Glauche ◽  
M. Bornhaeuser ◽  
I. Roeder
Keyword(s):  
Leukemic Cells ◽  
Individual Risk ◽  
Individual Treatment ◽  
Model Parameters ◽  
Quiescent State ◽  
Early Assessment ◽  
Hematopoietic Stem ◽  
Disease Response ◽  
Early Relapse ◽  
The Individual

AbstractDisease response and durability of remission are very heterogeneous in patients with acute myeloid leukaemia (AML) patients. There is increasing evidence that the individual risk of early relapse can be predicted based on the initial treatment response. However, it is unclear how such a correlation is linked to functional aspects of AML progression and treatment. We suggest a mathematical model in which leukaemia-initiating cells and normal/healthy hematopoietic stem and progenitor cells reversibly change between an active state characterized by proliferation and chemosensitivity and a quiescent state, in which the cells do not divide, but are also insensitive to chemotherapy. Applying this model to 275 molecular time courses of NPM1-mutated patients, we conclude that the differential chemosensitivity of the leukaemia-initiating cells together with the cells’ intrinsic proliferative capacity is sufficient to reproduce both, early relapse as well as long-lasting remission. We can, furthermore, show that the model parameters associated with individual chemosensitivity and proliferative advantage of the leukemic cells are closely linked to the patients’ time to relapse. They can, therefore, be used as a measure of the aggressiveness of the disease. Early assessment of these measures and incorporation into risk stratification schemes will improve risk assessment and individual treatment in AML.

scholarly journals Differential response to cytotoxic therapy explains treatment dynamics of acute myeloid leukaemia patients: insights from a mathematical modelling approach

2020 ◽  
Vol 17 (170) ◽  
pp. 20200091 ◽  
Author(s):  
H. Hoffmann ◽  
C. Thiede ◽  
I. Glauche ◽  
M. Bornhaeuser ◽  
I. Roeder
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Sampling Strategy ◽  
Complete Response ◽  
Early Response ◽  
Individual Risk ◽  
Model Parameters ◽  
Quiescent State ◽  
Early Relapse ◽  
Acute Myeloid

Disease response and durability of remission are very heterogeneous in patients with acute myeloid leukaemia (AML). There is increasing evidence that the individual risk of early relapse can be predicted based on the initial treatment response. However, it is unclear how such a correlation is linked to functional aspects of AML progression and treatment. We suggest a mathematical model in which leukaemia-initiating cells and normal/healthy haematopoietic stem and progenitor cells reversibly change between an active state characterized by proliferation and chemosensitivity and a quiescent state, in which the cells do not divide, but are also insensitive to chemotherapy. Applying this model to 275 molecular time courses of nucleophosmin 1 -mutated patients, we conclude that the differential chemosensitivity of the leukaemia-initiating cells together with the cells’ intrinsic proliferative capacity is sufficient to reproduce both, early relapse as well as long-lasting remission. We can, furthermore, show that the model parameters associated with individual chemosensitivity and proliferative advantage of the leukaemic cells are closely linked to the patients’ time to relapse, while a reliable prediction based on early response only is not possible based on the currently available data. Although we demonstrate with our approach, that the complete response data is sufficient to quantify the aggressiveness of the disease, further investigations are necessary to study how an intensive early sampling strategy may prospectively improve risk assessment and help to optimize individual treatments.

The Development of Language-Training Programs for Postrubella Hearing-Impaired Children

1973 ◽  
Vol 38 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Linda Lynch ◽  
Annette Tobin
Keyword(s):  
Hearing Impaired ◽  
Treatment Programs ◽  
Individual Treatment ◽  
Target Behaviors ◽  
Systematic Fashion ◽  
Development Of Language ◽  
The Individual ◽  
Impaired Children ◽  
Hearing Impaired Children

This paper presents the procedures developed and used in the individual treatment programs for a group of preschool, postrubella, hearing-impaired children. A case study illustrates the systematic fashion in which the clinician plans programs for each child on the basis of the child’s progress at any given time during the program. The clinician’s decisions are discussed relevant to (1) the choice of a mode(s) for the child and the teacher, (2) the basis for selecting specific target behaviors, (3) the progress of each program, and (4) the implications for future programming.

The importance and significance of gene polymorphisms in preeclampsia

2016 ◽  
pp. 45-49
Author(s):  
P.N. Veropotvelyan ◽  
◽  
I.S. Tsehmistrenko ◽  
N.P. Veropotvelyan ◽  
N.S. Rusak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Systematic Review ◽  
Early Diagnosis ◽  
Gene Polymorphisms ◽  
Individual Risk ◽  
Extended Study ◽  
Stress Genes ◽  
Detoxification System ◽  
The Individual ◽  
The Relationship

Was to conduct a systematic review of data on the relationship between polymorphisms genes of detoxification system and development of preeclampsia (РЕ). Рresents the main genes of detoxification system (GSTPI, GSTМI, GSTТI, GРХI, ЕРНХI, SOD-2, SOD-3, CYPIAL, MTHЕR, MTR) and their functions. Of interest is the possibility of calculating the individual risk of PE based on the results about the presence of a combination of different polymorphisms in the genotype of the female. Question about early diagnosis of РЕ remains controversial and not fully understood. It is necessary to conduct further in-depth, extended study of this problem. Key words: preeclampsia, oxidative stress, genes of the detoxification system.

Differentiation of endemic areas by incidence rates of tick-borne infectious diseases as the basis for choosing prevention strategy and tactics

2019 ◽  
pp. 56-61
Author(s):  
N.V. Rudakov ◽  
N.A. Penyevskaya ◽  
D.A. Saveliev ◽  
S.A. Rudakova ◽  
C.V. Shtrek ◽  
...  
Keyword(s):  
High Risk ◽  
Infectious Diseases ◽  
Population Based ◽  
Preventive Therapy ◽  
Incidence Rates ◽  
Prevention Strategy ◽  
Individual Risk ◽  
The Individual ◽  
Integral Assessment ◽  
Very High

Research objective. Differentiation of natural focal areas of Western Siberia by integral incidence rates of tick-borne infectious diseases for determination of the strategy and tactics of their comprehensive prevention. Materials and methods. A retrospective analysis of official statistics for the period 2002-2018 for eight sub-federal units in the context of administrative territories was carried out. The criteria of differentiation were determined by means of three evaluation scales, including long-term mean rates of tick-borne encephalitis, tick-borne borreliosis, and Siberian tick-borne typhus. As a scale gradation tool, we used the number of sample elements between the confidence boundaries of the median. The integral assessment was carried out by the sum of points corresponding to the incidence rates for each of the analyzed infections. Results. The areas of low, medium, above average, high and very high risk of tick-borne infectious diseases were determined. Recommendations on the choice of prevention strategy and tactics were given. In areas of very high and high incidence rates, a combination of population-based and individual prevention strategies is preferable while in other areas a combination of high-risk and individual strategies is recommended. Discussion. Epidemiologic zoning should be the basis of a risk-based approach to determining optimal volumes and directions of preventive measures against natural focal infections. It is necessary to improve the means and methods of determining the individual risk of getting infected and developing tick-borne infectious diseases in case of bites, in view of mixed infection of vectors, as well as methods of post-exposure disease prevention (preventive therapy).

scholarly journals A New Medical Record Proposal to the Prognostic Risk Assessment for MRONJ in Oncologic Patients: “Sapienza Head and Neck Unit” Proposal

2021 ◽  
Vol 18 (4) ◽  
pp. 1851
Author(s):  
Edoardo Brauner ◽  
Silvia Mezi ◽  
Alessandro Ciolfi ◽  
Chiara Ciolfi ◽  
Resi Pucci ◽  
...  
Keyword(s):  
Multidisciplinary Approach ◽  
Bone Cancer ◽  
Osteonecrosis Of The Jaw ◽  
Individual Risk ◽  
Medical Report ◽  
Oncologic Patients ◽  
Antiangiogenic Drugs ◽  
Dental Screening ◽  
The Individual

Medication-related osteonecrosis of the jaw (MRONJ) is an adverse event associated with antiresorptive and antiangiogenic drugs. The use of these drugs in the treatment of cancer patients with bone metastasis is necessary and standardized in the literature. A multidisciplinary approach for the patient’s management is strongly recommended. Therefore, it should be necessary to integrate the path of these subjects with a dedicated dental screening in order to first assess the individual risk of developing a MRONJ, and then to plan dental treatments and oral hygiene sessions, and finally to schedule a follow-up to intercept and treat early osteonecrosis. The aim of this manuscript is to propose a new simple medical report to evaluate patients affected by metastatic bone cancer in order to reduce the risk of developing MRONJ.

scholarly journals Myeloid-Derived Suppressor Cells and Mesenchymal Stem/Stromal Cells in Myeloid Malignancies

2021 ◽  
Vol 10 (13) ◽  
pp. 2788
Author(s):  
Suncica Kapor ◽  
Juan F. Santibanez
Keyword(s):  
Stromal Cells ◽  
Myeloid Leukemia ◽  
Chemotherapy Resistance ◽  
Leukemia Cell ◽  
Suppressor Cells ◽  
Leukemic Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Hematopoietic Stem ◽  
Myeloid Malignancies ◽  
Adaptive Immune Systems

Myeloid malignancies arise from an altered hematopoietic stem cell and mainly comprise acute myeloid leukemia, myelodysplastic syndromes, myeloproliferative malignancies, and chronic myelomonocytic leukemia. Myeloid neoplastic leukemic cells may influence the growth and differentiation of other hematopoietic cell lineages in peripheral blood and bone marrow. Myeloid-derived suppressor cells (MDSCs) and mesenchymal stromal cells (MSCs) display immunoregulatory properties by controlling the innate and adaptive immune systems that may induce a tolerant and supportive microenvironment for neoplasm development. This review analyzes the main features of MDSCs and MSCs in myeloid malignancies. The number of MDSCs is elevated in myeloid malignancies exhibiting high immunosuppressive capacities, whereas MSCs, in addition to their immunosuppression contribution, regulate myeloid leukemia cell proliferation, apoptosis, and chemotherapy resistance. Moreover, MSCs may promote MDSC expansion, which may mutually contribute to the creation of an immuno-tolerant neoplasm microenvironment. Understanding the implication of MDSCs and MSCs in myeloid malignancies may favor their potential use in immunotherapeutic strategies.

scholarly journals Development of the Mental, Emotional, and Bodily Toughness Inventory in Collegiate Athletes and Nonathletes

2008 ◽  
Vol 43 (2) ◽  
pp. 125-132 ◽  
Author(s):  
Mick G. Mack ◽  
Brian G. Ragan
Keyword(s):  
Undergraduate Students ◽  
Rating Scale ◽  
Collegiate Athletes ◽  
Rehabilitation Program ◽  
Mental Toughness ◽  
Individual Treatment ◽  
Model Data ◽  
Fit Statistics ◽  
The People ◽  
The Individual

Abstract Context: The assessment of an individual's mental toughness would assist clinicians in enhancing an individual's performance, improving compliance with the rehabilitation program, and improving the individual treatment program. However, no sound measure of mental toughness exists. Objective: To develop a new measure of mental toughness, the Mental, Emotional, and Bodily Toughness Inventory (MeBTough). Design: Participants were invited to complete a 45-item questionnaire. Setting: University research laboratory. Patients or Other Participants: A total of 261 undergraduate students were recruited to complete the questionnaire. Main Outcome Measure(s): The Rasch-calibrated item difficulties, fit statistics, and persons' mental toughness ability estimates were examined for model-data fit of the MeBTough. Results: Forty-three of the 45 items had good model-data fit with acceptable fit statistics. Results indicated that the distribution of items was fittingly targeted to the people and the collapsed rating scale functioned well. The item separation index (6.31) and separation reliability statistic (.98) provided evidence that the items had good variability with a high degree of confidence in replicating placement of the items from another sample. Conclusions: Results provided support for using the new measure of mental, emotional, and bodily toughness.

Prediction of pre-eclampsia

2021 ◽  
pp. 1753495X2098401
Author(s):  
Konstantinos Giannakou
Keyword(s):  
Early Recognition ◽  
Routine Care ◽  
Current Evidence ◽  
Individual Risk ◽  
Negative Consequences ◽  
Predictive Tool ◽  
Mortality And Morbidity ◽  
Maternal Mortality And Morbidity ◽  
Conducting Research ◽  
The Individual

Pre-eclampsia is a leading cause of neonatal and maternal mortality and morbidity that complicates approximately 2–8% of all pregnancies worldwide. The precise cause of pre-eclampsia is not completely understood, with several environmental, genetic, and maternal factors involved in its pathogenesis and pathophysiology. An accurate predictor of pre-eclampsia will facilitate early recognition, close surveillance according to the individual risk and early intervention, and reduce the negative consequences of the disorder. Current evidence shows that no single test predicts pre-eclampsia with sufficient accuracy to be clinically useful. A combination of markers into multiparametric models may provide a more useful and feasible predictive tool for pre-eclampsia screening in the routine care setting than a test of either component alone. This review presents a summary of the current advances on prediction of pre-eclampsia, highlighting their performance and applicability. Key priorities when conducting research on predicting pre-eclampsia are also analyzed.

Phase 1 and pharmacodynamic studies of G3139, a Bcl-2 antisense oligonucleotide, in combination with chemotherapy in refractory or relapsed acute leukemia

Blood ◽  
2003 ◽  
Vol 101 (2) ◽  
pp. 425-432 ◽  
Author(s):  
Guido Marcucci ◽  
John C. Byrd ◽  
Guowei Dai ◽  
Marko I. Klisovic ◽  
Peter J. Kourlas ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Lymphoblastic Leukemia ◽  
Phase 1 ◽  
Salvage Chemotherapy ◽  
Leukemic Cells ◽  
Electrolyte Imbalance ◽  
Mrna Levels ◽  
Disease Response ◽  
Unfavorable Clinical Outcome ◽  
State Concentration

Overexpression of Bcl-2 is a potential mechanism for chemoresistance in acute leukemia and has been associated with unfavorable clinical outcome. We hypothesized that down-regulation of Bcl-2 would restore chemosensitivity in leukemic cells. To test this hypothesis, we performed a phase 1 study of G3139 (Genasense, Genta, Berkeley Heights, NJ), an 18-mer phosphorothioate Bcl-2 antisense, with fludarabine (FL), cytarabine (ARA-C), and granulocyte colony-stimulating factor (G-CSF) (FLAG) salvage chemotherapy in patients with refractory or relapsed acute leukemia. Twenty patients with refractory or relapsed acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) were enrolled. G3139 was delivered by continuous infusion on days 1 to 10. FLAG chemotherapy was administered on days 5 to 10. Common side effects of this combination included fever, nausea, emesis, electrolyte imbalance, and fluid retention that were not dose limiting. Plasma pharmacokinetics of G3139 demonstrated steady-state concentration (Css) within 24 hours. Of the 20 patients, 9 (45%) had disease response, 6 (5 AML, 1 ALL) with complete remission (CR) and 3 (2 AML and 1 ALL) with no evidence of disease but failure to recover normal neutrophil and/or platelet counts or to remain in remission for at least 30 days (incomplete remission). Bcl-2 mRNA levels were down-regulated in 9 of the 12 (75%) evaluable patients. This study demonstrates that G3139 can be administered safely with FLAG chemotherapy and down-regulate its target, Bcl-2. The encouraging clinical and laboratory results justify the current plans for a phase 3 study in previously untreated high-risk AML (ie, age at least 60 years).

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