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Background Pediatric oncologists are often faced with situations in which parents or guardians refuse recommended treatment for curable childhood cancer. Deciding how to proceed in such situations is an ethical dilemma. The aim of this article is to consider optimal approaches when parents are strongly against oncological treatment, potentially compromising their childrens rights for health care and to the chance for cure. Cases In this paper, we report two cases of treatment refusal from our department and the impact of such decisions on the children themselves. Case no. 1 describes a child with retinoblastoma whose parents refused standard treatment in order to seek alternative treatment abroad. Case no. 2 describes a patient with a primary lymphoma of bone who received treatment by a court order after parental refusal. Conclusion When parents refuse a treatment for potentially curable cancer, the medical team often focuses on the certainty of death without treatment. In the background, there is a smaller but still significant risk that - even if the treatment is eventually accepted or compelled - the child will still die from treatment-related complications or refractory disease, possibly with considerable suffering. The reasons for refusing a treatment vary. The entire medical team is tasked with trying to respectfully understand the reasoning behind the parents unwillingness to accept the treatment, in order to address all possible misunderstandings and to propose solutions that could be acceptable for the parents. In some situations however, it is necessary to resolve the dilemma by legal means in order to protect the life of the child.Key words: oncology - ethics - decision making - treatment refusal - legal guardians The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 7. 8. 2017Accepted: 7. 9. 2017.

The relevance of the work lies in the justification of the need to pay attention to modern business on the development of consumer cooperation. The aim of the work is to describe the place and role of consumer cooperation in the modern Russian economy. Solving the work tasks carried out on the basis of application of scientific research methods within the comparative, logical and statistical analysis and through the analysis of the structure and dynamics of information. The result of this study was the proof of the need to revise the system of organization and financing of consumer cooperation in the modern Russian economy, including elements of public-cooperative partnership, leasing, franchising, outsourcing, raising funds of non-cooperative population, as well as the creation of a system of education of cooperative personnel.

Acute lymphoblastic leukemia (ALL) belongs to a genetically heterogeneous disease associated with a wide range of chromosomal and molecular changes. Determining these changes at the time of diagnosis can help the therapeutic decision, and contributes to the prediction of patients' clinical outcomes. A part of B-ALL (B-other) lacks cytogenetic abnormalities with clinical relevance for prognosis. Our first goal was to retrospectively review genetic results of patients from 2013-2017 and identify number of B-other patients in Slovak population. The second goal was to implement single nucleotide polymorphism (SNP) array analysis to improve the diagnosis and risk stratification. In this study we reviewed 133 B-ALL patients. We found that nearly 40% of them (52 cases) belonged to the B-other ALL group. Eighteen B-other ALL patients were subjected to the analysis using SNP-array. Overall, we identified 126 cytogenomic changes and in 4 patients the SNP array revealed clinically relevant markers of adverse prognosis and high relapse risk. Integrating identified genetic changes into clinical practice can bring improvement of prognosis assessment for children with ALL in Slovakia.

Juvenile myelomonocytic leukemia (JMML) is a rare, aggressive clonal myeloproliferative disorder of infancy and early childhood caused by oncogenic mutations in genes involved in the Ras pathway. Long-term survival has only been achieved with hematopoietic stem cell transplantation (HSCT), being able to cure more than 50% patients. To manage the disease before HSCT remains an important issue with constant searching for optimal treatment modalities. According to several retrospective analyses, azacitidine (AZA) induced clinical and molecular responses in patients with relapsed JMML pre-transplant and post-transplant, suggesting its use as a promising "bridging" therapy before HSCT. In this paper we report our first consecutive cohort of patients with JMML treated at our institution as well as our experience with the diagnosis, novel treatment and management of these patients before the HSCT. We present 6 patients with JMML, harboring different somatic mutations (PTPN11 and NRAS), with distinct clinical features; 3 of them had been treated with AZA 75 mg/m2 i.v. on days 1 to 7 of a 28-day cycle before the HSCT. Response to therapy was evaluated after each cycle in accordance with the International response criteria. One patient had a progression of splenomegaly during the treatment and after three cycles he was urgently transplanted. At the present, he is remaining in complete remission 3 years after HSCT. Two patients showed impressive response following the first cycle of the therapy with a regression of splenomegaly and monocyte count, normalized leukocytes, platelets and absent blasts in peripheral blood. The treatment was well tolerated with no adverse effect recorded. The clinical activity and favorable toxicity of AZA in JMML provide a rationale for its use as a "bridging" therapy before HSCT. Prospective trials with accompanying translational studies are required to provide further information regarding individual factors that may direct the most appropriate choice of pretransplantation therapy.

The article presents the results of a study of life meanings and values in connection with the life satisfaction of persons with drug addiction at the stage of rehabilitation. The urgency of the problem is determined by the fact that the statistics provided by the UN confirm that the number of people who use drugs is steadily increasing every year. In this regard, the issues of prevention of drug addiction and rehabilitation of addicts for the Russian society are today the most acute and represent a global problem. The results obtained in the study state that for drug addicts at the stage of rehabilitation, they begin to have a meaningful attitude to their life, positively assess the life path they have passed and the experience gained, considering it the beginning of a new stage in life, and make plans for the future. This fact may indicate the productivity of the rehabilitation program. They do not think about how much life in general is subject to control on their part. The respondents attach value to the very living of life, feel the need to be able to feel love in all its manifestations. Status and altruistic meanings are of the least importance in the respondents' system of life meanings. Hedonistic meanings of life prevail, acceptance of life as it is. Also, statistically significant relationships were found between the components of life meanings and values and the components of life satisfaction in drug addicts.

Today, the agro-industrial complex is the most important factor in the formation and development of the Russian economy. In the modern market economy of Russia, special attention is paid to the personality of the head of the agro-industrial complex. In connection with the development of the economy and technological progress, society is increasingly in need of an increase in the number of qualified and successful representatives of the management apparatus of this industry. On the basis of which we conducted an empirical study, where the object was 40 managers of various pilot production enterprises of the Rostov region. In the course of the empirical study, the following methods were used: “The scale of basic beliefs” (in the modification of M. A. Padun, A.V. Kotelnikova), Proactive coping inventory in the adaptation of E. Starchenkova, “Methods of coping behavior “ by R. Lazarus and S. Folkman, the Life Style Index (LSI). These recommendations can be taken into account by managers and employees of personnel services of enterprises of the agro-industrial complex when forming systems of motivation and development of the highest needs of employees holding managerial positions in modern market conditions.

The Last decades have witnessed elevated tension and conflicts in young people’s environment. There has been an increase in crime, terrorism, suicides, addictions, and other behavioral deviations among the young. Up to the 21st century, hostility was equated with aggression in its broad, non-differentiated sense. Today hostility is considered to be an inflexible and complex personality trait. Recent studies show that several genes can be viewed as genetic predictors of aggressiveness and hostility (Rodríguez-Ramos Á., Et al., 2019; Tkachenko O.N., 2016). The paper investigates the relationship between genotype and ethnicity as predisposing factors in manifesting hostile behavior. The study involved 320 participants - adolescents and young men of different ethnicity (Russians, Armenians, Dagestanis, Kabardians), aged from 12 to 19. Research methods: Buss-Durkee Hostility inventory (in the adaptation of Osnitsky A.K., 1998); isolation genomic DNA from buccal epithelial cells. Genotypes and alleles of the monoamine oxidase enzyme (MAOA) gene were considered as a candidate gene. Statistical analysis and data processing were performed using the PSPP 0.8 5. It was established that the low-active variant of the MAOA monoamine oxidase A gene (LPR) plays a significant role in determining the risk of hostile behavior. As far as the ethnic factor is concerned, low-level MAOA variants have significant differences in the populations of Russians compared with Dagestanis, or Kabardians. The results received contribute to understanding the relationships between genetics and behavior. It will help develop effective methods for the prevention of aggressive and hostile behavioral patterns.

Langerhans cell histiocytosis (LCH) is a histiocytic disorder driven by a constitutive activation of the MAPK signaling pathway in myeloid cells. In 50–60% of cases, it is caused by the BRAFV600E mutation. There is evidence that levels of BRAFV600E in the peripheral blood of patients with LCH correlate with disease burden and could be used as marker for disease extent and response to therapy. However, there is currently no consensus on how testing for minimal disseminated disease should be performed. Different approaches to determine the mutation load in patients with LCH were assessed and longitudinal evaluation of patient DNA during treatment with chemotherapy and/or the RAF inhibitor vemurafenib was performed. DNA was isolated from whole blood, different leukocyte subsets, and circulating cell-free DNA (ccf-DNA). We show that determining BRAF levels from whole blood is superior to using ccfDNA. Furthermore, it is important to identify the clinically relevant BRAF-mutated cellular subpopulations such as CD14+ monocytes or CD1c+ DCs, since other blood cells can also harbor the mutation and therefore confound whole blood or ccfDNA measurements. Our data support the view that single-agent treatment with an RAF inhibitor reduces disease activity but does not cure LCH.

Despite attempts to improve the definitions of ambiguous lineage leukemia (ALAL) during the last 2 decades, general therapy recommendations are missing. Herein, we report a large cohort of children with ALAL and propose a treatment strategy. A retrospective multinational study (International Berlin-Frankfurt-Münster Study of Leukemias of Ambiguous Lineage [iBFM-AMBI2012]) of 233 cases of pediatric ALAL patients is presented. Survival statistics were used to compare the prognosis of subsets and types of treatment. Five-year event-free survival (EFS) of patients with acute lymphoblastic leukemia (ALL)-type primary therapy (80% 6 4%) was superior to that of children who received acute myeloid leukemia (AML)-type or combined-type treatment (36% 6 7.2% and 50% 6 12%, respectively). When ALL- or AML-specific gene fusions were excluded, 5-year EFS of CD191 leukemia was 83% 6 5.3% on ALL-type primary treatment compared with 0% 6 0% and 28% 6 14% on AML-type and combined-type primary treatment, respectively. Superiority , of ALL-type treatment was documented in single-population mixed phenotype ALAL (using World Health Organization . and/or European Group for Immunophenotyping of Leukemia definitions) and bilineal ALAL. Treatment with ALL-type protocols is recommended for the majority of pediatric patients with ALAL, including cases with CD191 ALAL. AML-type treatment is preferred in a minority of ALAL cases with CD192 and no other lymphoid features. No overall benefit of transplantation was documented, and it could be introduced in some patients with a poor response to treatment. As no clear indicator was found for a change in treatment type, this is to be considered only in cases with ‡5% blasts after remission induction. The results provide a basis for a prospective trial. (Blood. 2018;132(3):264-276) © American Society of Hematology. All rights reserved.

Despite attempts to improve the definitions of ambiguous lineage leukemia (ALAL) during the last 2 decades, general therapy recommendations are missing. Herein, we report a large cohort of children with ALAL and propose a treatment strategy. A retrospective multinational study (International Berlin-Frankfurt-Munster Study of Leukemias of Ambiguous Lineage [iBFM-AMBI2012]) of 233 cases of pediatric ALAL patients is presented. Survival statistics were used to compare the prognosis of subsets and types of treatment. Five-year event-free survival (EFS) of patients with acute lymphoblastic leukemia (ALL)-type primary therapy (80% ± 4%) was superior to that of children who received acute myeloid leukemia (AML)-type or combined-type treatment (36% ± 7.2% and 50% ± 12%, respectively). When ALL- or AML-specific gene fusions were excluded, 5-year EFS of CD19+ leukemia was 83% ± 5.3% on ALL-type primary treatment compared with 0% ± 0% and 28% ± 14% on AML-type and combined-type primary treatment, respectively. Superiority of ALL-type treatment was documented in single-population mixed phenotype ALAL (using World Health Organization and/or European Group for Immunophenotyping of Leukemia definitions) and bilineal ALAL. Treatment with ALL-type protocols is recommended for the majority of pediatric patients with ALAL, including cases with CD19+ ALAL. AML-type treatment is preferred in a minority of ALAL cases with CD19- and no other lymphoid features. No overall benefit of transplantation was documented, and it could be introduced in some patients with a poor response to treatment. As no clear indicator was found for a change in treatment type, this is to be considered only in cases with ≥5% blasts after remission induction. The results provide a basis for a prospective trial.

The clinical characteristics of chronic myeloid leukemia (CML) in lymphoid blast crisis (BC) can resemble those of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL). Because of this, there can be concern as to whether a patient with newly diagnosed Ph leukemia has Ph ALL or CML in lymphoid BC. This distinction has significant potential therapeutic implications because most children with Ph ALL are now treated with chemotherapy plus a tyrosine kinase inhibitor, whereas allogeneic stem cell transplant is usually recommended for any patient with CML that presents in or later develops BC.

Introduction. Exophiala dermatitidisis a relatively common environmental black yeast with worldwide distribution and is a rare cause of fungal infection, mostly in patients with certain predisposing factors. Due to the rarity of the infection, little is known about the specific predisposing factors, way of infection or treatment. Case presentation. Here, we report what is to our knowledge the first case of E. dermatitidis infection in a child after allogeneic stem cell transplantation. We also review all paediatric cases reported in the literature since 1993. Conclusion. This is, to our knowledge, the first reported case of E. dermatitidis infection in a child after allogeneic stem cell transplantation. This report should increase the awareness of E. dermatitidis in immunocompromised paediatric patients, particularly after stem cell transplantation.

Magnusiomyces capitatus (previously known as Geotrichum capitatum or Blastoschizomyces capitatus or Trichosporon capitatum) is a rare cause of fungal infection in immunocompromised patients. Most of these cases (87%) have been reported from the Mediterranean region, as it is extremely rare to recognize it in other regions. Here we report a first case of disseminated M. capitatus infection in Slovakia. The patient – 19 year old woman with myelodysplastic syndrome was diagnosed with M. capitatus fungemia after allogeneic stem cell transplantation. The infection occurred despite antifungal prophylaxis with micafungin, which was in vitro sensitive to the yeast. The treatment according to minimal inhibitory concentrations (micafungin, voriconazol) and granulocyte transfusions were administered. M. capitatus was cleared out from the bloodstream. However, patient died of multiple organ failure. Autopsy showed multiple lesions in organs, but did not prove presence of yeast by histopathology. M. capitatus was confirmed by polymerase chain reaction from all tested organs: heart, brain, lungs, spleen, liver and kidneys. We present the post mortem pictures showing the yeast lesions in affected organs. 2012 Elsevier Ltd. All rights reserved.

Key Points Single-agent vemurafenib leads to a rapid and sustained clinical response in severe multisystem LCH but does not eradicate the disease. Longitudinal assessment of BRAF V600E during treatment shows that clinical remission can occur despite significant amounts of mutated BRAF.

Considers Anatoly Vasilyev’s creative work in the context of the unique artistic and poetic environment, the main role in which plays the concept «school - laboratory - theatre». To this day Anatoly Vasiliev, the famous Russian director, still engaged in search of technologies of that balance, as well as its aesthetic filling

The precise diagnosis of acute lymphoblastic leukemia is essential for correct prognosis assessment and therapy regimen selection. At present, immunophenotyping, cytogenetics and molecular screening are major and complementary methods utilized in a routine leukemia diagnostics. The aim of this study was to validate the application of multiplex reverse transcription-polymerase chain reaction (RT-PCR) assay for molecular diagnosis of the most common pediatric acute lymphoblastic leukemia-associated fusion transcripts. Our data show that screening of bone marrow and/or peripheral blood by RT-PCR, consisting of multiplex and monoplex PCR, confirmed results of real-time quantitative PCR (RT qPCR). This screening may provide a reliable, specific and sensitive method amenable to standard laboratory practice and a cost-effective alternative to more complex and expensive RT qPCR techniques.

BACKGROUND: Low grade gliomas (LGG) are the most frequent tumors of the central nervous system in children. Pediatric LGG are a heterogeneous set of tumors. They encompass tumors of astrocytic, oligodendroglial, and mixed glial-neuronal histology, and are classified according to the World Health Organization (WHO). METHODS: The objective of our study was to analyze the outcome of patients with LGG from the Department of Pediatric Hematology and Oncology in Bratislava, Slovakia treated in period from January 2000 up to December 2015. The cohort consisted of 139 patients with LGG, 83 boys/56 girls. RESULTS: The most common histological type was pilocytic astrocytoma (WHO grade I) in 64 children. Primary surgery was performed in 102 children and 72 from these do not need any further therapy. Forty eight patients received chemotherapy first or other line therapy. Radiotherapy was used 26 times. In our study median follow up was 82,3 months and overall survival for the whole cohort was 97,2%. CONCLUSION: In pediatric low grade glioma surgery is the mainstay of therapy. Ten year overall survival rates for patients whose tumors are completely resected are 90% or greater. Chemotherapy is reserved for progressive or recurrent tumors. Radiotherapy can also improve OS but is associated with more frequent adverse effects. Recent advent of integrated genomics and NGS has implicated the activation of RAS/RAF/MEK pathway in tumor genesis of LGG. Many of these biological advances are changing treatment paradigma, particularly in low-grade gliomas, where rationale targeted therapies are currently being explored in clinical trials.

The article presents the results of a comprehensive study of psychological characteristics of the manifestation of co-dependent behavior of women. The novelty of the study lies in the development of psychodiagnostics criteria for identifying co-dependent behavior using the content analysis method, using the Thematic Apperceptive Test (TAT) tables with the aim of further developing a set of therapeutic measures. The study involved 152 women from the Rostov region of the Russian Federation aged 17 to 30 years, exhibiting varying degrees of codependence and living with a drug-dependent partner for at least 5 years. The study was carried out using standardized psychological tests and projective methods, which made it possible to identify the degree of manifestation of co-dependent behavior: test “The scale of co-dependence in relations (Spann Fisher)” (adaptation Moskalenko); “Write a story” technique (stimulus material of tables 2, 4 and 6 of TAT. It has been established that content analysis allows us to determine qualitative differences in the degree of manifestation of co-dependent behavior, which we can identify and use in the initial stage of therapy with a co-dependent client, which means that it allows not only to quickly identify the condition, but also to determine its intensity.

One of the most famous projective techniques around the world – G. Rorschach inkblot test. In many countries this technique is rather popular because it can give the chance of both the qualitative and quantitative analysis. This thesis is confirmed in research works of J. Eksner Institute. For several decades J. Eksner Institute (USA) have been collected psychometric data with using Rorschach test in various groups of the population. These studies make it possible to conduct a clinical and psychological studies and determine the mental status of the subject. Our research is devoted to informational content of Rorschach test of women who have difficulties in interpersonal interaction within their family (with an addictive partner). It was shown that with increase of manifestation intensity of codependent behavior also the orientation of codependent women in interpersonal interaction changes, the coding symbols (determinants), specific for the codependent women, in answers to the third table of Rorschach test (an integrative system of J. Eksner) were also revealed. The practical relevance of this research is that the obtained results can form a basis of express diagnostics of the women having difficulties in interpersonal interaction within the family (husbands, children).

Introduction L’histiocytose langerhansienne (HCL) est une pathologie essentiellement pediatrique au pronostic tres variable. La mutation somatique BRAF (V600E), identifiee dans 38 a 64 % des cas, est associee aux formes severes et chimioresistantes. Dans plusieurs centres europeens, les enfants atteints d’HCL refractaire mutee BRAF (V600E) sont traites par vemurafenib (VMU), therapie ciblee anti-BRAF. Les effets indesirables cutanes (EIC) du VMU sont connus chez l’adulte, mais n’ont pas ete etudies chez l’enfant. Les objectifs de cette etude etaient d’evaluer, chez les enfants traites par VMU pour HCL, la frequence des EIC, leur severite et leur impact sur la poursuite du VMU. Materiel et methodes Etude retrospective sur la cohorte europeenne d’enfants traites par VMU en monotherapie pour HCL refractaire mutee BRAF V600E entre octobre 2013 et janvier 2018. Resultats Trente-huit enfants inclus : âge median 2,2 ans [0,2–20,4], sex-ratio 0,65, duree mediane de traitement 183,5 jours [20–759], dose mediane de VMU 21 mg/kg/j [12,9–41,4]. Trente enfants (78,9 %) presentaient au moins un EIC : rash folliculaire (39,5 %) ( Fig. 1 ), photosensibilite (28,9 %), xerose (26,3 %), keratose pilaire (23,7 %) et panniculite neutrophilique (15,8 %) ( Fig. 2 ). Trois enfants (7,8 %) presentaient un angiœdeme. La majorite des EIC etaient de grade 1 (65,8 %) ou 2 (26,8 %). On observait 3,7 % de grade 3, aucun grade 4 ou 5. Un seul EIC (1,2 %) entrainait l’arret definitif du VMU (phototoxicite et angiœdeme recidivant, reintroduction non contre-indiquee mais refusee par la patiente). Une reduction de dose etait necessaire dans 10,9 % des cas, un arret temporaire dans 6,0 % des cas. Aucune tumeur cutanee, toxidermie severe ni syndrome main pied n’etait observe. Discussion Comme chez l’adulte, les EIC etaient frequents, rarement severes, avec un impact limite sur la poursuite du traitement. La frequence de chaque type d’EIC observee etait comparable a celle decrite chez l’adulte. Les angiœdemes, observes ici dans 7,8 % des cas, ne sont pas decrits chez l’adulte. Les autres particularites sont l’absence de syndrome main pied, de toxidermie severe et de tumeur cutanee induite. Ces dernieres sont liees a une activation paradoxale de la voie MAPK dans les cellules NRAS mutees. Les mutations NRAS cutanees, UV induites, sont probablement rares chez les enfants en bas âge, ce qui pourrait expliquer l’absence de tumeur cutanee induite chez l’enfant. Les limites de cette etude sont le caractere retrospectif, l’absence de groupe controle et un effectif peu important. Conclusion Comme chez l’adulte, les EIC sont frequents mais rarement graves avec un impact limite sur la poursuite du traitement. Aucune tumeur cutanee induite n’etait observee dans cette etude. Un suivi dermatologique mensuel reste indispensable pour gerer les EIC et depister des possibles tumeurs cutanees paradoxales.

Background The classification of acute myeloid leukemia (AML) FAB subtype M7 relies on immunophenotypic assessment. CD41 is expressed throughout all stages of maturation of megakaryocytes and has therefore been described as a specific blast cell marker in AML M7 as well as in transient myeloproliferative disease (TMD) of patients with Down syndrome (DS). However, technical difficulties underlie the need for new markers for these entities. Methods We evaluated the expression of human lymphocyte function-associated antigen 1 (CD11a) in a large cohort of pediatric AML and TMD patients (n = 91) of the Austrian AML-BFM 98 and 2004 studies. Results We found a consistent deficiency of CD11a as assessed by mean fluorescence intensity in all patients with non-DS AML M7 (n = 8) and M6 (n = 1), all cases of classical DS-AML (n = 12) as well as TMD (n = 15) that was statistically significant in comparison to non-DS AML M0-M5 patients (n = 55; P < 0.001, sensitivity 100%). Only three of 55 Non-DS M0-5 patients were CD11a deficient (specificity 95%). Monocytic leukemias (M4/5) and normal monocytes typically showed a high CD11a expression, FAB types M1/2 and normal neutrophils an intermediate expression level, while all M3 leukemias were rather low in CD11a expression. Conclusions We conclude, that deficiency of CD11a expression should be added to the diagnostic criteria of AML-M7, classical DS-AML and TMD. © 2013 International Clinical Cytometry Society

The gene encoding β-mannanase (EC 3.2.1.78) BaMan26A from the bacterium Bifidobacterium adolescentis (living in the human gut) was cloned and the gene product characterized. The enzyme was found to be modular and to contain a putative signal peptide. It possesses a catalytic module of the glycoside hydrolase family 26, a predicted immunoglobulin-like module, and two putative carbohydrate-binding modules (CBMs) of family 23. The enzyme is likely cell attached either by the sortase mechanism (LPXTG motif) or via a C-terminal transmembrane helix. The gene was expressed in Escherichia coli without the native signal peptide or the cell anchor. Two variants were made: one containing all four modules, designated BaMan26A-101K, and one truncated before the CBMs, designated BaMan26A-53K. BaMan26A-101K, which contains the CBMs, showed an affinity to carob galactomannan having a dissociation constant of 0.34 μM (8.8 mg/liter), whereas BaMan26A-53K did not bind, showing that at least one of the putative CBMs of family 23 is mannan binding. For BaMan26A-53K, k cat was determined to be 444 s −1 and K m 21.3 g/liter using carob galactomannan as the substrate at the optimal pH of 5.3. Both of the enzyme variants hydrolyzed konjac glucomannan, as well as carob and guar gum galactomannans to a mixture of oligosaccharides. The dominant product from ivory nut mannan was found to be mannotriose. Mannobiose and mannotetraose were produced to a lesser extent, as shown by high-performance anion-exchange chromatography. Mannobiose was not hydrolyzed, and mannotriose was hydrolyzed at a significantly lower rate than the longer oligosaccharides.

Background Acute myeloid leukemia (AML) in children is rare, and it is generally considered to be more resistant to chemotherapy than acute lymphoblastic leukemia. However, because of the gradual intensification of chemotherapy and better supportive care, outcomes have improved considerably over the past 20 years. The management of children with AML in the Slovak Republic was unified and centralized during the second half of the 1990s with the introduction of Berlin-Frankfurt-Munster (BFM) protocols. In 2000, the AML-BFM-1998 protocol was introduced, and data collection became centralized.

Bacterial infection is the most common complication in paediatric oncological patients during cancer treatment. A suitable tool for early prediction of unfavourable course of infection is still needed. We performed a prospective longitudinal observational study to evaluate of the role of serum biomarkers (C-reactive protein, procalcitonin, interleukin-6, presepsin) in the early diagnosis of bacteraemia (gram-negative versus gram-positive) in patients with haematological malignancies. We observed 69 febrile episodes in 33 patients (17 male, 16 female; 1.5-18.9 years, mean 7.31 years, median 5 years). Within this sample, there were 22 cases of positive blood cultures, 16 cases of sepsis, 38 cases of fever with no signs or symptoms of sepsis, and two deaths from infectious complications. All markers tested had good negative predictive value (73% - 93%). CRP was characterized by good specificity for registration bacteraemia (96%, 95% CI: 85% - 99%), but other results were inconclusive. We identified comparably balanced sensitivity (64% - 81%) and specificity (61% - 88%) for interleukin-6 and procalcitonin, and we proved their quality to predict positive blood culture and clinical signs of sepsis as well. Patients with gram-negative bacteraemia had significantly elevated levels of PCT and IL-6 in comparison with a group of patients with gram-positive bacteraemia (p = 0.04 for PCT and p = 0.005 for IL-6). Presepsin was characterized by poor specificity (27%, 95% CI: 15% - 43%) and positive predictive value (24%, 95% CI: 12 - 39%) for predicting bacteraemia, and by better sensitivity (84%, 95% CI: 55% - 98%) and specificity (58%, 95% CI: 42% - 73%) for predicting clinical signs of sepsis.

Children with Down syndrome (DS) up to the age of 4 years are at a 150-fold excess risk of developing myeloid leukemia (ML-DS). Approximately 4%-5% of newborns with DS develop transient myeloproliferative disorder (TMD). Blast cell structure and immunophenotype are similar in TMD and ML-DS. A mutation in the hematopoietic transcription factor GATA1 is present in almost all cases. Here, we show that simple techniques detect GATA1 mutations in the largest series of TMD (n = 134; 88%) and ML-DS (n = 103; 85%) cases tested. Furthermore, no significant difference in the mutational spectrum between the 2 disorders was seen. Thus, the type of GATA1 sequence mutation is not a reliable tool and is not prognostic of which patients with TMD are probable to develop ML-DS.

Research has exposed cancer to be a heterogeneous disease with a high degree of inter-tumoral and intra-tumoral variability. Individual tumors have unique profiles, and these molecular signatures make the use of traditional histology-based treatments problematic. The conventional diagnostic categories, while necessary for care, thwart the use of molecular information for treatment as molecular characteristics cross tissue types. This is compounded by the struggle to keep abreast the scientific advances made in all fields of science, and by the enormous challenge to organize, cross-reference, and apply molecular data for patient benefit. In order to supplement the site-specific, histology-driven diagnosis with genomic, proteomic and metabolomics information, a paradigm shift in diagnosis and treatment of patients is required. While most physicians are open and keen to use the emerging data for therapy, even those versed in molecular therapeutics are overwhelmed with the amount of available data. It is not surprising that even though The Human Genome Project was completed thirteen years ago, our patients have not benefited from the information. Physicians cannot, and should not be asked to process the gigabytes of genomic and proteomic information on their own in order to provide patients with safe therapies. The following consensus summary identifies the needed for practice changes, proposes potential solutions to the present crisis of informational overload, suggests ways of providing physicians with the tools necessary for interpreting patient specific molecular profiles, and facilitates the implementation of quantitative precision medicine. It also provides two case studies where this approach has been used.