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Visfatin (VF) is an adipocytokine that performs many functions, including enhancing cell proliferation and biosynthesis of nicotinamide mononucleotides and dinucleotides. It also seems to be involved in the development of glucose metabolism disturbances. The goal of the study was the determination of VF concentrations in children with leukemia who are treated with stem cell transplantation. VF concentrations were measured in plasma before and after oral glucose tolerance test (OGTT; 60 and 120 minutes) in 22 children with leukemia treated with hematopoietic stem cell transplantation (HSCT) and healthy control subjects (n = 24). The HSCT group was studied twice: before HSCT (22 children) and approximately 6 months after HSCT (12 of 22 children). After fasting, concentrations of glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein, and high-sensitivity C-reactive protein (hsCRP) were determined. Significantly lower (p < 0.05) median values of VF concentrations at all time points in the OGTT were found in pre- HSCT children compared with control subjects. The median VF concentration was significantly higher after HSCT compared with before HSCT. The decrease in VF in leukemic children in complete remission may be caused by myelosuppression and immunosuppression after prolong chemotherapy and is beneficial because of the decrease in its antiapoptotic activity. VF can serve as an additional biochemical marker for remission in patients with leukemia. Normalization of plasma VF concentration after HSCT might be caused by a process of immune reconstitution and prolonged inflammation (e.g., infections, graft-versus-host disease), injury to organs (e.g., lungs, gut, liver), and endocrinology deficiencies., (Copyright © 2014 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)

Introduction: patients treated with hematopoietic stem cell transplantation (HSCT) lose immune memory accumulated through a lifetime. They are at increased risk of developing infections with microorganisms such as Haemophilus influenza, Streptococcus pneumoniae and others for which vaccines are available. Therefore, all patients after HSCT should be routinely revaccinated. Systemic reimmunization after HSCT is a relatively neglected area especially in countries which have not national recommendations and there is lack of systemic regulations in health care system., Objective: the rate of immunization before transplantation and the persistence of vaccine-specific antibodies after HSCT was assessed., Study Design: a group of38 children after stem cell transplantation (19 autologous, 19 allogeneic) was studied., Results: only a few patients completed standard vaccination protocol before HSCT. At the median time of 29 (range: 6-67) months after autologous and 13 (range: 8-33) months after allogeneic HSCT, when the revaccination was commenced, the majority of children had concentration of antibody lower than the minimum protective thresholds. That was 82% for tetanus, 71% for Hib and varicella, 46% for HBV and 38% for diphtheria., Conclusions: all HSCT recipients should be routinely revaccinated to stimulate the immunity to the vaccine-preventable diseases.

Chronic granulomatous disease (CGD) is phagocytic cell metabolic disorder resulting in recurrent infections and granuloma formation. This paper reports the favourable outcome of allogeneic transplantation in six high-risk CGD patients. The following donors were used: HLA-matched, related (two) and unrelated (three), and HLA-mismatched, unrelated (one). One patient was transplanted twice using the same sibling donor because of graft rejection at 6 months after reduced-intensity conditioning transplant (fludarabine and melphalan). Myeloablative conditioning regimen consisted of busulphan and cyclophosphamide. Stem cell source was unmanipulated bone marrow containing: 5.2 (2.6-6.5) × 10(8) nucleated cells, 3.8 (2.0-8.0) × 10(6) CD34+ cells and 45 (27-64) × 10(6) CD3+ cells per kilogramme. Graft-versus-host disease prophylaxis consisted of cyclosporine A and, for unrelated donors, short course of methotrexate and anti-T-lymphocyte globulin. Mean neutrophile and platelet engraftments were observed at day 22 (20-23) and day 20 (16-29), respectively. Pre-existing infections and inflammatory granulomas resolved. With the follow-up of 4-35 months (mean, 20 months), all patients are alive and well with full donor chimerism and normalized superoxide production.

Currently, granulocyte colony stimulating factor (G-CSF) alone or in combination with myelosuppresive chemotherapy remain the standards of CD34+ cells mobilization allows the safe and successful collection of adequate peripheral blood stem cells (PBSC) for autologous transplantation. However, in up to 30% of patients mobilization of PBSC is ineffective. This report presents our experience in mobilization and collection of peripheral blood stem cells in 82 children with different proliferative disease. In mobilization G-CSF was administered alone in steady state (56 patients, pts) or in combination with myelosuppresive chemotherapy (26 pts). The CD34+ cell count at least 10 cells/ml was required to start apheresis procedure, which was repeated, if needed, during following 1-4 days until collection of at least 2 (optimally 3) x106 CD34+ cells/kg b.w. of recipient was obtained. Three pts in each group (3/ 56 and 3/26) failed the first course of mobilization. The median number of CD34+ cells mobilized was 4.8 (0.5-15) x106/kg b.w. The minimal and optimal number of CD34+ cells for transplantation was achieved in 85% and 61% of patients in the G-CSF + chemotherapy group and in 84% and 54% in the G-CSF group, respectively. The efficacy of presented mobilization arms in our group was similar. However, the incidence of infection and total hospitalization time during mobilization were higher in chemotherapy + G-CSF group.

In departments of neurology, neurosurgery and hospice care there is a group of patients with compete motor function impairment having normal central nervous system function. Victims of spinal cord injury, cerebral palsy, cerebral stroke, loss of extremities, neuromuscular diseases, between others belong to them. Since two decades an intensive studies of use of brain waves to steer peripheral equipments has been performed. Brain Computer Interface and Brain-Machine Interface will allow in the near future for even partial restore of skills in permanently disabled patients. Recently new sets composed of games steered by brain waves have been introduced to the market. Exercises with such equipment will help to control an ability to concentrate and precise steer of the peripheral electronic equipments. The next phase will be use of the new skills to steer the wheelchairs and other computer programs with the brain signals to control own healthy organs or artificial machines.

Unlabelled: The aim of the study was the evaluation of safety and efficacy of vaccination in children after stem cell transplantation., Patients and Methods: 21 patients, 1.4-22 (average 7.8) years old, 13 boys and 8 girls after autologous (11-52%) and allogeneic (10-48%) transplantation were included in the vaccination protocol. Indications for transplantation were: neoplastic disease--16, immunodeficiencies--3 and aplastic anaemia 2 cases. Time between transplantation and beginning of vaccination protocol was 0.8-4 (average 1.5) years. Vaccination protocol was constructed on the basis of the European Group for Blood and Marrow Transplantation indications. We have evaluated: (1) quality of recipient immune reconstitution and protection against common pathogens (2) immunogenicity of revaccination schedule; (3) safety of the vaccination programme., Results: With the exception of one patient presenting with repeated fever, lymph node enlargement, muscle and joint pain, no important side effects were observed. Meningococcial meningitis developed in one patient who refused vaccination. The mean concentrations of antibodies in the plasma before and after vaccination were as follows: anti-diphteria (54; 2285), anti-tetanus (136; 3149) and anti-hepatitis B virus (anti-HBs: 24; 474) IU/ml., Conclusions: (1) Vaccination in patients after transplantation is efficient and well tolerated. (2) Significant increase of antibody level was detected. (3) Any delay in beginning the vaccination can result in life threatening complications.

Infections are one of the most important clinical problem and most frequent cause of interventions among chronically ill children under hospice care. Frequent and long-lasting hospitalizations before admission to the hospice cause patients' colonization with nosocomial pathogens. These pathogens usually cause returning infections, difficult to cure in home care. The aim of the study was evaluation of colonization by multidrug-resistant organisms and infections' frequency in chronically and incurably ill children under care of the Cracow Children's Hospice of Father J. Tischner. We analyzed infections in patients of the Hospice in 2008-2009. Frequency of infections, their localization, pathogens and necessity of hospitalization were evaluated. On the basis of microbiological examination we distinguished infections caused by multidrug resistant pathogens. Ninety microbiological examination were made in 24 children. Urine, stool, pharyngeal and nasal swap and others were examined. Nosocomial pathogens including Gram-negative rods with ESBL phenotype, Gram-positive Enterococci with HLAR phenotype and Staphylococci with MRCNS and MRSA phenotype were isolated in 36 (40%) examinations, in 17 (71%) patients. Frequency of infections was higher in patients colonized by nosocomial pathogens in comparison with patients without colonization, but difference was not statistically important. There are many factors that increase risk of infections and make them difficult to treat, like: immobilization, impaired swallowing and coughing reflexes, thorax deformation, neurogenic bladder, tracheostomy. Multi-drug resistant pathogens are additional risk factor that can lead to the necessity of hospitalization. In chronically and incurably ill patients time of hospitalization should be minimized to reduce the risk of colonization with multi-drug resistant pathogens.

Congenital and acquired neurodegradative diseases are always the reason for prolonged stay in hospital, at the beginning of the establishment of diagnosis and treatment and afterwards for stabilizing all functional adaptation to an existence with the severe disability. Also infections of the lower respiratory tract accompanying the later course of the disease are usually directed to hospital treatment. The aim of the study was to delineate the role of hospice care of patients staying at home, in economical approach to the medical care of severly and incurably ill children. The study group consisted of 29 children with neurodegradative diseases, aged 6 months to 18 years, admitted to the home care of Priest Józef Tischner Cracovian Children' Hospice. The costs of yearly treatment (based on 2008 data) of the infections of the lower airways in the studied group, performed at home under the hospice care and in hospital, were compared. The actual expenses of home treatment were counted. Considering the hospital therapy costs, the simulation was performed following median expenses of a 10-day-treatment of a 20 kg-in-weight child with uncomplicated lower respiratory tract infection in pediatric department with the use of the first line therapy antibiotic. Three parameters were taken to calculations: the medical care costs, the expenses of laboratory tests and X-ray pictures and the costs of antibiotics. In studied children 61 cases of lower respiratory tract infections were diagnosed in 2008 (the median incidence was 2,1 per year; ranged 0-7), of which 48 cases were treated at home. The median time of antibiotics administration in home treatment was 13 days. In 31% of infections more than one antibiotic was used. In 19% of cases in home therapy parenteral medicine was necessary. The median summarized cost of treat- ment at home was calculated as 2657 zl. The need for hospital care in our group concerned 13 incidences. The median estimated cost of treatment of the lower airways infection in hospital for one child equaled 4942 zl. The expenses of home treatment of the lower airways infections under the hospice care were twice lower than the costs of the therapy in hospital. Apart from the obvious psychological and social benefits, also economic aspect contributes to the promotion of the hospice care of staying-at-home patient in the improvement of medical care for children with severe neurodegradative diseases.

OS is a variant of SCID characterized by generalized erythroderma, alopecia, eosinophilia, and elevated IgE levels. It is fatal unless treated with allogeneic HSCT, which is the only curative approach. However, treatment related complications and graft rejection are major obstacles to the success of treatment. In this report, we describe a patient with OS, complicated by prolonged cytomegalovirus infection, successfully treated by reduced intensity conditioning allogeneic HSCT from sibling donor.

Rhabdomyosarcoma is a highly metastatic tumor, mostly observed in children and adolescence. When diagnosed at early stages it is mostly curable. However, in advanced or metastatic stages the 5-years survival rate is below 20%. Thus, new treatment strategies for this tumor are needed. In this paper we showed that HSP90 inhibitors, geldanamycin and its analogs, can profoundly affect proliferation of rhabdomyosarcoma cells. We also showed that blocking of HSP90 function induces apoptosis of tumor cells and downregulates expression of anti apoptotic protein AKT. Cells exposed to geldanamycin and its analogs exhibit strong reduction of MET receptor expression and subsequent inhibition of HGF-dependent tumor cells migration and invasion. Interestingly, at concentrations sufficient to block tumor cells growth and motility, the 17AEP-GA, 17AAG and 17DMAP-GA were not toxic or only slightly toxic toward normal hematopoietic, mesenchymal and endothelial cells. This could be due to low HSP90 expression both at mRNA and protein level in these cells. Collectively, our findings suggest that blocking HSP90 action through geldanmycins could be in the future a part of new therapeutic strategies in rhabdomyosarcoma treatment.

In this study, geldanamycin (GA) was found to have an antiproliferative effect on both embryonal and alveolar rhabdomyosarcoma (RMS) cell lines. The maximum level of inhibition reached 80% for both embryonal and alveolar RMS. After GA treatment, cells also became apoptotic as judged by Annexin V-positive staining, activation of caspase-3 pathway and poly(ADP ribose) polymerase cleavage. GA was responsible for the arrest of RMS cells in both G1 and G2/M phases of the cell cycle. G1 blockade, however, was transient and was seen only in the first 24 h of GA treatment. RMS often gives distant metastases to various organs including bone marrow. RMS cells express high levels of MET receptor and respond to hepatocyte growth factor with increased motility. In our study, we found that GA decreased the level of MET expression and inhibited the chemotaxis of RMS cells toward the hepatocyte growth factor gradient. GA also blocked the homing of RMS cells into bone marrow of severe combined immune deficient mice. In all our experiments embryonal RMS cell lines were significantly more sensitive, and lower concentrations of GA were sufficient to block embryonal RMS cell proliferation, induce apoptosis and inhibit motility. Our data show that the HSP90 inhibitor GA has the potential to become a new drug in RMS treatment. It blocks RMS proliferation, decreases cell survival and inhibits motility of RMS cells.

Toxocariasis was diagnosed in 3 out of 22 children (14%) treated in our center with high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). The patients were coming from rural areas in the southeastern Poland and did not present any clinical symptoms of toxocariasis upon admission to the hospital. Although no neurological and ophthalmological abnormalities were noticed, the atypical form of toxacariasis was diagnosed based on elevated eosinophils counts, positive serological tests, and biochemical symptoms of liver damage. The authors conclude that toxocariasis should be taken into consideration in the differential diagnosis of eosinophilia in children undergoing high-dose chemotherapy and HSCT, especially if they are coming from rural areas.