Long-Term Immune Recovery After Hematopoietic Stem Cell Transplantation for ADA Deficiency: a Single-Center Experience

Unconditioned hematopoietic stem cell transplantation (HSCT) is the recommended treatment for patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency with an HLA-matched sibling donor (MSD) or family donor (MFD). Improved overall survival (OS) has been reported compared to the use of unrelated donors, and previous studies have demonstrated that adequate cellular and humoral immune recovery can be achieved even in the absence of conditioning. Detailed insight of the long-term outcome is still limited. We aim to address this by studying a large single-center cohort of 28 adenosine deaminase-deficient patients who underwent a total of 31 HSCT procedures, of which more than half were unconditioned. We report an OS of 85.7% and event-free survival of 71% for the entire cohort, with no statistically significant differences after procedures using related or unrelated HLA-matched donors. We find that donor engraftment in the myeloid compartment is significantly diminished in unconditioned procedures, which typically use a MSD or MFD. This is associated with poor metabolic correction and more frequent failure to discontinue immunoglobulin replacement therapy. Approximately one in four patients receiving an unconditioned procedure required a second procedure, whereas the use of reduced intensity conditioning (RIC) prior to allogeneic transplantation improves the long-term outcome by achieving better myeloid engraftment, humoral immune recovery, and metabolic correction. Further longitudinal studies are needed to optimize future management and guidelines, but our findings support a potential role for the routine use of RIC in most ADA-deficient patients receiving an HLA-identical hematopoietic stem cell transplant, even when a MSD or MFD is available.

Choice of tactics of combined treatment of patients with malignant diseases of colon

The aim. To determine the definition of nutritional extinction and its characteristics in various phases of carcinogenesis, to show the role of nutritional counseling in the selection of personalized metabolic correction programs.Materials and methods. 107 patients with pancreatic head adenocarcinoma (T3 and T4). In addition to traditional methods, the nutritional status was assessed according to the parameters of the well-known personalized alimentary-volemic diagnosis and the main common metabolic syndromes (inflammatory, hypermetabolism-hypercatabolism, toxic-anemic, anorexia-cachexia).Results. The phases of nutritional extinction are identified, in accordance with which the original schemes of metabolic correction are developed. The effectiveness of the programs used, calculated according to the degree of well-being, was significantly higher in comparison with standard solutions. The feasibility of using this tactic was confirmed (in addition to traditional tests) by measuring the metabolism in lysosomes (according to the analysis of the level of cathepsin L using ELISA in the blood serum of the considered groups of patients).Conclusions. 1) When determining the tactics of nutritional treatment of cancer patients, it is advisable to distinguish the phases of nutritional extinction, on the basis of which to carry out a differentiated metabolic correction. 2) The role of nutritional counseling (along with consulting with a surgeon and an anesthesiologist) allows you to clarify the strategy of treatment of patients with oncological pathology, and in some cases, make adjustments to the choice of the nature of the surgical aid.

Evaluation of the efficacy of levocarnitine in supporting therapy in multiple myeloma

The accompanying therapy prescribed during the use of toxic drugs helps patients to complete the treatment to the end, and the doctor adheres to the treatment of the chosen line The aim of the study was to study the effect of levocarnitine on blood biochemical parameters and on chemotherapy tolerance. Materials and methods. The study was conducted in the stem cell treatment department at Republican Specialized Scientific Practical Medical Center of Hematology . Chemotherapy toxicity was assessed according to WHO and NCIC standards. Results. In a comparative study, 30 patients receiving chemotherapy for myeloma with varying degrees of toxicity when fortecarnite (100 mg / kg / day) was added to standard therapy for 2 months or more showed a significant positive change in cytochemical parameters (Alanin transferase (ALT), aspartat transferase (AST)), which allowed the authors recommend metabolic correction to all patients receiving chemotherapy, especially with 2nd and 3rd degree of toxicity.

STUDY OF THE TOXIC EFFECT ON THE ORGANISM OF WHITE RATS AND RABBITS OF THE COMPOSITION OF MEDICINES

The article presents materials on the study of the toxicity of a complex of therapeutic and prophylactic agents, including choline chloride, succinic acid, xymedon, sorbitol, a suspension of lactic and propionic acid microorganisms, on the organism of laboratory animals in the experiment on white rats and rabbits. Based on the results of primary screening, the agent is recommended for eliminating the consequences of animal toxicosis, hepatoprotection and metabolic correction. Ac-cording to the results of the studies, it was found that this composition, in accordance with the ex-isting classification, is low-toxic, does not have a local irritating effect on the mucous membranes of the eyes and skin, does not possess cumulative properties, therefore, has prospects for further re-search.

Full transcriptome analysis of gene expression in liver of mice in a comparative study of quercetin efficiency on two obesity models

BACKGROUND: Quercetin (Q; 3,3',4',5,7 - pentahydroxyflavone) can help alleviate the pathological effects of nutritional obesity and metabolic syndrome when taken as part of products for special dietary needs and food supplements. The mechanisms of action of Q at the genetic level are not well understood.AIMS: To study gene expression in liver tissue of mice with alimentary and genetically determined obesity upon intake of Q with diet.MATERIALS AND METHODS: During 46 days of the experiment on 32 male C57Bl/6J mice fed a diet with an excess of fat and fructose and 24 male genetically obese db/db mice the effect of Q in dose of 25 or 100 mg/kg of body weight was studied on differential expression of 39430 genes in mice livers by full transcriptome profiling on microchip according to the Agilent One-Color Microarray-Based Gene Expression Analysis Low Input Quick Amp Labeling protocol (version 6.8). To identify metabolic pathways (KEGGs) that were targets of Q exposure, transcriptomic data were analyzed using bioinformatics methods in an “R” environment.RESULTS: Differences were revealed in the nature of Q supplementation action in animals with dietary induced and genetically determined obesity on a number of key metabolic pathways, including the metabolism of lipids and steroids (Saa3, Cidec, Scd1, Apoa4, Acss2, Fabp5, Car3, Acacb, Insig2 genes), amino acids and nitrogen bases (Ngef, Gls2), carbohydrates (G6pdx, Pdk4), regulation of cell growth, apoptosis and proliferation (Btg3, Cgref1, Fst, Nrep Tuba8), neurotransmission (Grin2d, Camk2b), immune system reactions (CD14i, Jchain, Ifi27l2b).CONCLUSIONS: The data obtained help to explain the ambiguous effectiveness of Q, like other polyphenols, in the dietary treatment of various forms of obesity in humans, as well as to form a set of sensitive biomarkers that allow us to elucidate the effectiveness of minor biologically active food substances in preclinical trials of new means of metabolic correction of obesity and metabolic syndrome.