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Inflammatory bowel disease, encompassing Crohn's disease and ulcerative colitis, is a persistent immune-mediated inflammatory gastrointestinal disease. This study investigates the role of growth differentiation factor 15 in severe IBD cases, aiming to identify a reliable parameter to assess disease severity and monitor activity. We analyzed plasma samples from 100 patients undergoing biologic therapy for severe IBD and 50 control subjects. Our analysis included evaluations of GDF-15 levels, inflammatory markers, and clinical features. We employed statistical methods such as the Mann-Whitney U test, ANOVA, and Spearman's correlation for an in-depth analysis. Our results demonstrated consistently higher GDF-15 levels in patients with both Crohn's disease and ulcerative colitis compared to the control group, irrespective of the biologic treatment received. The correlation analysis indicated significant relationships between GDF-15 levels, patient age, fibrinogen, and IL-6 levels. This study positions GDF-15 as a promising biomarker for severe IBD, with notable correlations with age and inflammatory markers. These findings underscore GDF-15's potential in enhancing disease monitoring and management strategies in an IBD context and encourage further research to clarify GDF-15's role in the IBD pathophysiology.
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BACKGROUND: COVID-19 is a viral disease notorious for frequent worldwide outbreaks. It is difficult to control, thereby resulting in overload of the healthcare system. A possible solution to prevent overcrowding is rapid triage of patients, which makes it possible to focus care on the high-risk patients and minimize the impact of crowding on patient prognosis. METHODS: The triage algorithm assessed self-sufficiency, oximetry, systolic blood pressure, and the Glasgow coma scale. Compliance with the triage protocol was defined as fulfillment of all protocol steps, including assignment of the correct level of care. Triage was considered successful if there was no change in the scope of care (e.g., unscheduled hospital admission, transfer to different level of care) or if there was unexpected death within 48 hours. RESULTS: A total of 929 patients were enrolled in the study. Triage criteria were fulfilled in 825 (88.8%) patients. Within 48 hours, unscheduled hospital admission, transfer to different level of care, or unexpected death occurred in 56 (6.0%), 6 (0.6%), and 5 (0.5%) patients, respectively. The risk of unscheduled hospital admission or transfer to different level of care was significantly increased if triage criteria were not fulfilled [13.1% vs. 76.1%, RR 5.8 (3.8-8.3), p < 0.001; 0.5% vs. 5.2%, RR 11.4 (2.3-57.7), p = 0.036, respectively]. CONCLUSION: The proposed algorithm for triage of patients with proven COVID-19 is a simple, fast, and reliable tool for rapid sorting for outpatient treatment, hospitalization on a standard ward, or assignment to an intensive care unit.
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COVID-19 , Humanos , COVID-19/epidemiología , Triaje/métodos , Servicio de Urgencia en Hospital , Hospitalización , Unidades de Cuidados IntensivosRESUMEN
BACKGROUND: Pathogen reduction technology (PRT) may improve the safety of RBCs for transfusion. As the Czech Republic considers PRT, we asked what effects riboflavin and UV light PRT pre-freezing has on the post-thaw recovery and properties of cryopreserved RBCs (CRBCs) after deglycerolization and liquid storage. STUDY DESIGN AND METHODS: 24 Group O whole blood (WB) units were leukoreduced and then treated with riboflavin and UV light PRT (Mirasol, Terumo BCT, USA) before cryopreservation (T-CRBC); 20 similarly-collected units were untreated controls (C-CRBC). Units were processed to RBCs and then cryopreserved with 40% glycerol (wt/vol), frozen at -80°C, stored >118 days, reconstituted as deglycerolized RBC units in AS-3, and stored at 4 ± 2°C for 21 days. One treated unit sustained massive hemolysis during the post-thaw wash process and was removed from data analysis. The remaining units were assessed pre-PRT, post-PRT, and post-thaw-wash on days 0, 7, 14, and 21 for hematocrit, volume, hemoglobin per transfusion unit, pH, % hemolysis, hemoglobin in the supernatant, potassium, phosphorus, NH3 , osmolality, ATP, and 2,3-diphosphoglycerate. RESULTS: PRT with leukoreduction caused a 5% loss of RBC followed by a 24% freeze-thaw-wash related loss for a total 28% loss but treated units contained an average of 45 g of hemoglobin, meeting European Union guidelines for CRBC. T-CRBCs displayed higher post-wash hemolysis, potassium, and ammonia concentrations, and lower ATP at the end of storage. CONCLUSIONS: Cryopreserved RBCs from Riboflavin and UV light-treated WB meet the criteria for clinical use for 7 days after thawing and provide additional protection against infectious threats.
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Hemólisis , Rayos Ultravioleta , Humanos , Congelación , Conservación de la Sangre , Eritrocitos , Criopreservación , Hemoglobinas/análisis , Riboflavina/farmacología , Adenosina Trifosfato , Potasio/análisisRESUMEN
BACKGROUND: Pathogen reduction technology (PRT) is increasingly used in the preparation of platelets for therapeutic transfusion. As the Czech Republic considers PRT, we asked what effects PRT may have on the recovery and function of platelets after cryopreservation (CP), which we use in both military and civilian blood settings. STUDY DESIGN AND METHODS: 16 Group O apheresis platelets units were treated with PRT (Mirasol, Terumo BCT, USA) before freezing; 15 similarly collected units were frozen without PRT as controls. All units were processed with 5-6% DMSO, frozen at - 80 °C, stored > 14 days, and reconstituted in thawed AB plasma. After reconstitution, all units were assessed for: platelet count, mean platelet volume (MPV), platelet recovery, thromboelastography, thrombin generation time, endogenous thrombin potential (ETP), glucose, lactate, pH, pO2, pCO2, HCO3, CD41, CD42b, CD62, Annexin V, CCL5, CD62P, and aggregates > 2 mm and selected units for Kunicki score. RESULTS: PRT treated platelet units had lower platelet number (247 vs 278 ×109/U), reduced thromboelastographic MA (38 vs 62 mm) and demonstrated aggregates compared to untreated platelets. Plasma coagulation functions were largely unchanged. CONCLUSIONS: Samples from PRT units showed reduced platelet number, reduced function greater than the reduced number would cause, and aggregates. While the platelet numbers are sufficient to meet the European standard, marked platelets activation with weak clot strength suggest reduced effectiveness.
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Eliminación de Componentes Sanguíneos , Rayos Ultravioleta , Humanos , Trombina , Conservación de la Sangre , Plaquetas/fisiología , Riboflavina/farmacología , Ácido Láctico , CriopreservaciónRESUMEN
OBJECTIVES: The aim of this cross-sectional study was to investigate the determinants of COVID-19 vaccine acceptance in University of Defence members. BACKGROUND: Vaccination is the most important method of prevention against COVID-19 and achieving sufficient vaccination rate is thus essential to maintain the military capability. METHODOLOGY: An online questionnaire was distributed electronically to 2,408 respondents in autumn 2021. The survey was designed to collect demographic predictors of vaccination, data on motivation and reasons for refusing vaccination. RESULTS: A total of 626 completed questionnaires were analyzed, of which 557 (89 %) were vaccinated and 69 (11 %) were unvaccinated respondents. The most significant predictors of vaccine acceptance were: concern about COVID-19 (OR 2.44, p < 0.001), history of COVID-19 (OR 0.39, p = 0.001). The most frequently cited motives for vaccination were health protection (74.7 %) and an easier social life (69.1 %), while concerns about vaccine safety and vaccine adverse effects (79.1 %) followed by lack of confidence in vaccine efficacy (68.7 %) were the main reasons for vaccine refusal. CONCLUSION: To increase the vaccination rate it is necessary to target the younger population and increase awareness of vaccine safety and efficacy. If these measures are not sufficient to encourage voluntary vaccine acceptance, consideration should be given to making vaccination mandatory for selected professional groups (Tab. 5, Fig. 1, Ref. 25).
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Vacunas contra la COVID-19 , COVID-19 , Enfermedades Profesionales , Vacilación a la Vacunación , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Estudios Transversales , República Checa , Humanos , Motivación , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/etiología , Enfermedades Profesionales/prevención & control , VacunaciónRESUMEN
The aim of the present study was to evaluate the significance of low-level minimal/measurable residual disease (MRD) during early consolidation treatment in adult BCR-ABL1-negative acute lymphoblastic leukaemia. The MRD load was monitored by immunoglobulin/T-cell receptor rearrangements and assessed as negative [complete MRD response (CMR)], positive non-quantifiable (MRDnq) and positive quantifiable (MRDq). MRDnq before the first and second consolidation blocks had a comparable negative effect on survival as MRDq. The 5-year overall survival for CMR, MRDnq and MRDq at week 11 was 74·0%, 42·3% and 35·0% respectively. No central nervous system infiltration and MRD at week 11 were independent prognostic factors for survival on multivariate analysis (hazard ratios 0·32 and 2·25).
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Biomarcadores de Tumor , Proteínas de Fusión bcr-abl/genética , Neoplasia Residual/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adulto , Factores de Edad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia de Consolidación , Manejo de la Enfermedad , Femenino , Humanos , Quimioterapia de Inducción , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Resultado del TratamientoRESUMEN
OBJECTIVE: The article deals with occupational health protection and identification of health risks in the work environment of the Ministry of Defence (MoD) of the Czech Republic (CR). It focuses on the assessment of the incidence of occupational diseases (OD) in high-risk and risk-free occupational categories in the years 2010-2019 and compares them with data from the civilian sector. It identifies the differences between military staff and civilian employees of the MoD. METHODS: From the records of OD at the Department of Occupational Diseases of the Central Military Hospital in Prague, the data on acknowledged OD from the years 2010 to 2019 were obtained and then a retrospective analysis focusing on the classification of work at risk was performed. The obtained data were compared with the data from the Czech National Registry of Occupational Diseases (NROD), which are published annually by the National Institute of Public Health. RESULTS: In the years under review, 191 OD were confirmed at the area of MoD, 26% of all OD occurred in employees classified in the occupational risk category. Compared with the data in the NROD, where 50% of OD were found to have been caused by high-risk work, the incidence of OD caused by high-risk work in professional soldiers is lower. Only 1.6% of all OD occurred in professional soldiers whose work was classified as high-risk one. In civilian employees of MoD 24.6% of all OD were connected with high-risk work. On the contrary, the proportion of OD occurring in professional soldiers working in risk-free categories was 57.6%, in civilian employees of MoD was the ratio much lower - 16.2%. CONCLUSION: Work at the Ministry of Defence was not adequately categorized, therefore, in 2020 a new categorization of work was introduced, which together with preventive measures could contribute to reducing the incidence of OD at the Ministry of Defence.
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Personal Militar , Enfermedades Profesionales , Humanos , República Checa/epidemiología , Estudios Retrospectivos , Enfermedades Profesionales/epidemiología , OcupacionesRESUMEN
INTRODUCTION: BCR-ABL1-like acute lymphoblastic leukemia (ALL) is a high-risk disease with a complex genomic background. Though extensively studied, data on the frequency and mutual associations of present mutations are still incomplete in adult patients. This retrospective study aims to map the genomic landscape of B-other ALL in a cohort of adult patients with a focus on the BCR-ABL1-like ALL subtype. METHODS: We analyzed bone marrow and peripheral blood samples of adult B-other ALL patients treated consecutively at three major Czech teaching hospitals. Samples were analyzed by cytogenetic methods, gene expression profiling, multiplex ligation-dependent probe amplification (MLPA), and next-generation sequencing (NGS). RESULTS: Fifty-eight B-other ALL patients (not BCR-ABL1, KMT2A-rearranged, ETV6-RUNX1, TCF3-PBX1, or iAMP21) were included in the study. Median follow-up was 23.8 months. Samples from 33 patients were available for a gene expression analysis, 48.9% identified as BCR-ABL1-like ALL. Of the BCR-ABL1-like ALL cases, 18.8% harbored IGH-CRLF2 and 12.5% P2RY8-CRLF2 fusion gene. We observed a higher MRD failure rate in BCR-ABL1-like than in non-BCR-ABL1-like ALL patients after the induction treatment (50.0 vs. 13.3%, p=.05). There was a trend to worse progression-free and overall survival in the BCR-ABL1-like group, though not statistically significant. Deletions in IKZF1 gene were found in 31.3% of BCR-ABL1-like cases. Patients with concurrent IKZF1 and CDKN2A/B, PAX5 or PAR1 region deletions (IKZF1plus profile) had significantly worse progression-free survival than those with sole IKZF1 deletion or IKZF1 wild-type (p=.02). NGS analysis was performed in 54 patients and identified 99 short variants in TP53, JAK2, NRAS, PAX5, CREBBP, NF1, FLT3, ATM, KRAS, RUNX1, and other genes. Seventy-five of these gene variants have not yet been described in B-cell precursor ALL to date. CONCLUSION: This study widens existing knowledge of the BCR-ABL1-like and B-other ALL genomic landscape in the adult population, supports previous findings, and identifies a number of novel gene variants.
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Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Estudios de Cohortes , Perfilación de la Expresión Génica , Genómica , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Estudios RetrospectivosRESUMEN
INTRODUCTION: Our study aim was to assess how the macronutrient intake during total parenteral nutrition (TPN) modulates plasma total free fatty acids (FFAs) levels and individual fatty acids in critically ill patients. METHOD: Adult patients aged 18-80, admitted to the intensive care unit (ICU), who were indicated for TPN, with an expected duration of more than three days, were included in the study. Isoenergetic and isonitrogenous TPN solutions were given with a major non-protein energy source, which was glucose (group G) or glucose and lipid emulsions (Smof lipid; group L). Blood samples were collected on days 0, 1, 3, 6, 9, 14, and 28. RESULTS: A significant decrease (p < 0.001) in total FFAs occurred in both groups with a bigger decrease in group G (p < 0.001) from day 0 (0.41 ± 0.19 mmolâL-1) to day 28 (0.10 ± 0.07 mmolâL-1). Increased palmitooleic acid and decreased linoleic and docosahexaenoic acids, with a trend of increased mead acid to arachidonic acid ratio, on day 28 were observed in group G in comparison with group L. Group G had an insignificant increase in leptin with no differences in the concentrations of vitamin E, triacylglycerides, and plasminogen activator inhibitor-1. CONCLUSION: Decreased plasma FFA in critically ill patients who receive TPN may result from increased insulin sensitivity with a better effect in group G, owing to higher insulin and glucose dosing and no lipid emulsions. It is advisable to include a lipid emulsion at the latest from three weeks of TPN to prevent essential fatty acid deficiency.
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Enfermedad Crítica/terapia , Ácidos Grasos no Esterificados/sangre , Glucosa/administración & dosificación , Lípidos/administración & dosificación , Nutrición Parenteral Total/métodos , Anciano , Emulsiones/administración & dosificación , Ácidos Grasos Esenciales/sangre , Ácidos Grasos Esenciales/deficiencia , Femenino , Humanos , Resistencia a la Insulina/fisiología , Unidades de Cuidados Intensivos , Leptina/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos , alfa-Tocoferol/sangreRESUMEN
BACKGROUND: Acute myeloid leukemia (AML) cells are highly resistant to chemotherapeutic drugs. Cytokines and adhesion molecules may contribute to this resistance and affect treatment outcome. The aim of this study was to evaluate the independence and additional prognostic information of baseline serum levels of selected cytokines and soluble adhesion molecules, included in analyses with standard prognostic indicators. METHODS: We used biochip array technology to measure levels of selected cytokines and soluble adhesion molecules in serum samples of 80 newly diagnosed AML patients. The markers of tumour microenvironment were analysed against high risk karyotype, hyperleucocytosis, higher age, lactic dehydrogenase levels and presence of FLT3-ITD and NPM-1 mutation. RESULTS: All evaluated analytes were independent of standard prognostic indicators. Fifteen were associated with overall and eight with progression-free survival in univariate analysis. After correction for multiple testing, we identified soluble interleukin-2 receptor-α as an independent indicator of overall survival. Further, the soluble type I TNF-α receptor was close to statistical significance for both overall and progression-free survival. CONCLUSIONS: Baseline levels of soluble interleukin-2 receptor-α predict overall survival in newly diagnosed AML. The TNF-α type I soluble receptor is a candidate prognostic marker in AML and is worth of further investigation.
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Moléculas de Adhesión Celular/sangre , Citocinas/sangre , Interleucina-2/sangre , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/mortalidad , Femenino , Humanos , Interleucina-2/genética , Leucemia Mieloide Aguda/genética , Masculino , Persona de Mediana Edad , Mutación/genética , Pronóstico , Supervivencia sin Progresión , Microambiente Tumoral/fisiologíaRESUMEN
Abundant drinking of fluids at any occasion became popular in wealthy society in last decades. It is referred to asserted beneficial health effects, but rationale of these recommendations is disputed in expert environment as hardly traceable and tenable. Authors of the article analyse theoretical issues as well as empiric literary evidence for the current popular recommendation. They find them unfounded and difficult to be defended and the risks of transitive hypo-hydration overestimated. Moreover, they alert true risks of water poisoning we meet not quite rarely in common practice.
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Deshidratación , Desequilibrio Hidroelectrolítico , Ingestión de Líquidos , Medicina Basada en la Evidencia , Humanos , Equilibrio HidroelectrolíticoRESUMEN
BACKGROUND: Minimal residual disease (MRD) is an important prognostic maker in acute lymphoblastic leukemia (ALL). However, few data comparing the measurement of adult ALL MRD using different methods in daily practice are available. We conducted an analysis comparing the importance of flow cytometry (FCM) and real-time quantitative polymerase chain reaction (PCR) in the assessment of MRD in adult ALL. PATIENTS AND METHODS: Fifty-six consecutive adult patients with both Philadelphia-negative and -positive ALL treated according to an intensive protocol were enrolled in the study. Bone marrow samples were acquired on day 26 and during week 11 of treatment. MRD evaluation was performed using 8-color FCM and PCR of immunoglobulin or T-cell receptor gene clonal rearrangements and BCR-ABL1, KMT2A-AF4 and E2A-PBX1 fusion genes. RESULTS: On day 26, both FCM and PCR seemed to have good discrimination sensitivity for overall survival (P = .001 to .008) and progression-free survival (P = .03 to .04) prediction for both Philadelphia-positive and -negative cases. The most sensitive method in week 11 was PCR including all results > 0 considered to indicate MRD positivity (P = .002 for overall survival and P = .02 for progression-free survival). PCR with other cutoffs was not sufficiently sensitive in week 11. Moreover, no FCM+ samples were found in week 11. The subanalysis of the Philadelphia-negative patients showed similar results. CONCLUSION: Our analysis showed that both FCM and PCR MRD assessment methods are sensitive for survival prediction during induction. However, we believe FCM could not be sufficiently sensitive in later phases of treatment.
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Citometría de Flujo/métodos , Neoplasia Residual/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Trasplante de Células Madre/efectos adversos , Adolescente , Adulto , Anciano , Médula Ósea , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasia Residual/etiología , Neoplasia Residual/metabolismo , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
OBJECTIVE: The aim of the present study was to assess long-term prognostic value of high on-treatment platelet reactivity (HTPR) in patients after acute myocardial infarction (MI) and its association with possible risk factors. METHODS: This prospective, case-control study was an observation of 198 patients who had acute MI. Response to aspirin and clopidogrel was assessed using impedance aggregometry. Patients were divided into groups of adequate response, dual poor responsiveness (DPR), poor responsiveness to aspirin (PRA), and poor responsiveness to clopidogrel (PRC). Simultaneously, potential risk factors of HTPR development were recorded. After 5 years, MI recurrence and overall mortality were assessed. RESULTS: HTPR was more frequent in New York Heart Association Class III and IV patients, and in patients with left ventricle systolic dysfunction. Five-year mortality rate was higher in all groups of patients with HTPR compared to patients with sufficient response to antiplatelet treatment: in PRA patients, 38.1% vs. 19.2%, p<0.01; in PRC patients, 45.2% vs. 17.3%, p<0.001; and in DPR patients, 50.0% vs. 19.9%, p<0.05. Risk of repeat MI also increased (hazard ratio [HR] 4.0, p<0.05 for DPR group; HR 4.37, p<0.01 for PRA group; and HR 3.25, p<0.05 for PRC group). CONCLUSION: PRA, PRC, and DPR are independent predictors of increased 5-year mortality and risk of repeat non-fatal MI. The study has demonstrated that HTPR is frequently observed in patients with severe heart failure and left ventricle systolic dysfunction.
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Plaquetas/fisiología , Infarto del Miocardio/epidemiología , Anciano , Aspirina/uso terapéutico , Estudios de Casos y Controles , Clopidogrel/uso terapéutico , República Checa/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/mortalidad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Prospectivos , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
BACKGROUND AND AIMS: Despite high-dose multi-agent chemotherapy and allogeneic stem cell transplantation, the relapse rate of acute myeloid leukemia (AML) is high. Further, the disease is highly resistent to drugs. We speculated that deeper understanding of AML-endothelial cell interactions might provide new targets for selective modulation of the AML microenvironment and form the basis for novel treatment approaches. In this study, we evaluated levels of endothelium derived soluble adhesion molecules in active disease and in complete remission (CR) and their relationship with inflammatory cytokines. METHODS: Baseline serum levels of 25 cytokines and 5 soluble adhesion molecules were measured in 84 AML patients using biochip array technology. CR samples were evaluated in 44 patients of this cohort. The control group consisted of 15 healthy blood donors. RESULTS: All analytes were independent of age or disease origin. Some correlations were restricted to active AML, some were ubiquitous and some were found in remission. In active disease, E-selectin (E-SEL) and VCAM-1 correlated with leukocyte count, E-SEL correlated with P-selectin (P-SEL). Platelet count related to IL-7, EGF and VEGF but not to P-SEL. In CR, P-SEL correlated with platelet count and EGF but not with E-SEL. There was no relationship of P-SEL and E-SEL in the control group. CONCLUSIONS: Leukemic activity is associated with a different pattern of soluble adhesion molecule levels. Both E-SEL and P-SEL may be derived from endothelial cells. Their levels correlated in active disease. E-SEL correlated with leukocyte count. In CR, P-SEL physiologically correlated with platelet count. The correlation with E-SEL was insignificant and absent in the control group. Our data suggest activation of endothelial cells in the presence of myeloblasts.
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Moléculas de Adhesión Celular/metabolismo , Células Endoteliales/fisiología , Células Precursoras de Granulocitos/fisiología , Leucemia Mieloide Aguda/sangre , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Citocinas/metabolismo , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVES: Acute myeloid leukemia (AML) cells are highly resistant to therapy. The presumed molecular basis of this resistance is the effect of tumor necrosis factor alpha (TNF-α) and other cytokines on endothelial adhesion molecule expression. The aim of this study was to test the hypothesis that cytokines and soluble adhesion molecules correlate in AML. METHODS: Baseline serum levels of 17 cytokines and 5 soluble adhesion molecules were measured in 53 AML patients using biochip array technology. Age, leukocyte count, secondary AML, CRP, FLT3-ITD and remission were variables. Statistical analysis was performed in R version 3.1.2. RESULTS: VCAM-1 correlated with ICAM-1 (P < 0.0001), E-selectin (P < 0.0001), leukocyte count (P = 0.0005) and TNF-α (P = 0.0035). E-selectin correlated with leukocyte count (P < 0.0001), P-selectin (P = 0.0032) and MCP-1 (P = 0.0119). CRP correlated with IL-6 (P < 0.0001), leukocyte count negatively correlated with IL-7 (P = 0.0318). FLT3-ITD was associated with higher E-selectin (P = 0.0010) and lower IL-7 (P = 0.0252). Secondary AML patients were older. Failure of induction therapy was associated with significantly higher CRP and lower P-selectin. Leukocyte count (P < 0.0001), FLT3-ITD (P = 0.0017) and secondary AML (P = 0.0439) influenced the principal component. CONCLUSIONS: Leukemic cells can modulate the microenvironment. Cytokine, adhesion molecule levels and leukocyte count correlate in AML. Understanding these mechanisms may form the basis of novel therapeutic approaches.
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Moléculas de Adhesión Celular/metabolismo , Citocinas/metabolismo , Leucemia Mieloide Aguda/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/fisiología , Tirosina Quinasa 3 Similar a fms/fisiología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos , Femenino , Humanos , Leucemia Mieloide Aguda/sangre , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Análisis de Componente Principal , Estudios ProspectivosRESUMEN
AIMS: To compare serum levels of 17 cytokines and 5 adhesion molecules in patients with newly diagnosed acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) using biochip array technology. METHODS: A total of 15 AML and 15 ALL patients were studied. Serum samples were taken prior to anticancer therapy and were analyzed by biochip based immunoassays on the Evidence Investigator analyzer. This approach allows simultaneous detection of multiple analytes from a single sample. T-tests were used for statistical analysis. RESULTS: Comparing cytokine and adhesion molecules levels in newly diagnosed AML and ALL patients, we found significant increase in AML in serum IL-4 (P < 0.0001), IL-2 (P < 0.01), IL-3 (P < 0.05), and significant decrease (P < 0.05) in serum VEGF and VCAM-1. DISCUSSION: Our results indicate that serum profile of cytokines and adhesion molecules differs in newly diagnosed AML and ALL patients. Further studies are needed to establish if these alterations could be used as a clinically relevant biomarker for acute leukemias.
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Biomarcadores de Tumor/metabolismo , Moléculas de Adhesión Celular/metabolismo , Leucemia Mieloide Aguda/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Adulto , Citocinas/metabolismo , Diagnóstico Diferencial , Femenino , Humanos , Leucemia Mieloide Aguda/sangre , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Análisis por Matrices de Proteínas/métodos , Adulto JovenRESUMEN
BACKGROUND: The treatment of malignancies like acute myeloid leukemia (AML) is often complicated by the heterogeneity of the disease and the mechanisms of the disease progression. This heterogeneity is often not reflected in standard treatment approaches which provide predictable outcomes in the majority of patients but fail in individual cases even with high-dose multi-agent chemotherapy regimens and allogeneic stem cell transplantation. Further, the unselective effect of chemotherapy causes high treatment-related toxicity and accelerates the risk of infection during prolonged pancytopenia, preventing further dose escalation. Despite rapid progress in therapeutic strategies, the fatality of high-grade malignancies remains enormous. OBJECTIVES: Adhesive interactions trigger signal transduction pathway activation and this prevents the apoptosis of both normal and malignant cells. A correlation between expression of defined adhesion molecules and patient outcome has been found for several malignant diseases including AML. We aim to describe how disruption of these signalling pathways can overcome the high resistance to treatment and increase the selectivity of targeting malignant cells. This could effectively reduce the overall treatment-related toxicity and improve the general outcome. CONCLUSIONS: Adhesion molecules facilitate growth of malignant diseases. This review provides a deeper insight into these processes. Modulation of adhesion molecules-mediated interactions is an innovative and feasible approach in treatment of AML and many other malignancies. Due to expected low toxicity it is an acceptable addition to standard chemotherapeutical regimens for all age groups of patients. This approach could improve the overall treatment outcome in the future.
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Moléculas de Adhesión Celular , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/terapia , Terapia Combinada , Humanos , PronósticoRESUMEN
BACKGROUND: Cardiotoxicity is a well-known and potentially serious complication of anticancer therapy. Anthracycline-based chemotherapy represents the greatest risk. Early detection of cardiotoxicity is crucial for applying preventive and supportive therapeutic strategies. METHODS AND RESULTS: Various methods have been recommended for monitoring of cardiotoxicity. In our conditions, echocardiography and electrocardiography are routinely used. However, this approach shows low sensitivity for the early prediction of cardiomyopathy when the possibilities of appropriate management could still improve the patient's outcome. Recently, biomarkers of cardiac injury have been investigated in the assessment of chemotherapy-induced cardiotoxicity. Cardiospecific biomarkers, such as cardiac troponins, show high diagnostic efficacy in the early subclinical phase of the disease before the clinical onset of cardiomyopathy. Increase in their concentrations correlates with disease severity. As for natriuretic peptides, some studies, including ours, have shown promising results. Definitive evidence of their diagnostic and prognostic role in this context is still lacking and natriuretic peptides have not been routinely used for monitoring of cardiotoxicity in clinical practice. Other perspective biomarkers of cardiotoxicity in oncology are under study, especially heart-type fatty acid-binding protein (H-FABP) and glycogen phosphorylase BB (GPBB). Our studies using GPBB have provided encouraging results. However, the available data are limited and their practical use in this context cannot be recommended until their clinical efficacy is clearly defined. CONCLUSIONS: This review covers the current status of biomarkers for the early detection of anthracycline-induced cardiotoxicity. The authors present in brief, their own experience with multiple biomarkers in the detection of cardiotoxicity.
Asunto(s)
Antraciclinas/efectos adversos , Antibióticos Antineoplásicos/efectos adversos , Biomarcadores/análisis , Cardiotoxicidad/diagnóstico , Cardiotoxicidad/etiología , HumanosRESUMEN
AIMS: Evaluation of serum levels of 17 cytokines and 5 adhesion molecules in patients treated for acute myeloid leukemia (AML) using biochip array technology. This approach allows multi-analytical determination from a single sample. METHODS: A total of 15 AML patients were studied. Blood samples were taken at the diagnosis (active leukemia) and at circa 6 months after completion of last chemotherapy (durable complete remission in all patients). RESULTS: Comparing cytokine and adhesion molecule levels in active leukemia and in durable complete remission, we found significant increase (P<0.01) in serum interleukin-7 (IL-7), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and significant decrease (P<0.01) in serum E-selectin. DISCUSSION: Our results indicate that serum levels of specific cytokines and adhesion molecules (IL-7, EGF, VEGF, E-selectin) are significantly altered in patients treated for AML, reflecting activity of the disease. Further investigation is needed to establish if the changes observed in the levels of these molecules could be used as a prognostic indicator of AML.