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Oncological patients are especially predisposed to fungal infections due to multiple risk factors and immunocompromising treatment. Epidemiological research regarding pediatric oncologic patients is still insufficient, and existing data are difficult to generalize on different populations. Therefore, we aimed to analyze fungal infections and fungal epidemiology in the Department of Oncology and Hematology of the University Children’s Hospital in Krakow with help from the Clinical Microbiology Department. During the chosen period of 2005 and 2015–2020, 2342 tests were performed in our ward on 847 patients. Analyzed samples were divided into five source groups. The amount of patients with positive test results was 62.5%. The year with the highest detection level was 2005. The most frequent pathogen was Candida albicans, with a significant decrease in tendency. An increase in non-albicans species was observed. Candida parapsilosis was not frequently observed compared to similar studies. We noticed an increase in positive results from the urinary tract material. Our results confirmed that fungal infections are still an issue, and they may indicate the efficacy of prophylaxis. The majority of our results are consistent with the literature, yet we managed to emphasize data unique to our patients’ population. Our findings are helpful in clinical work and for further studies in our center.

Insulin-like growth factors (IGF-1 and IGF-2) and insulin-like growth factor-binding proteins (IGFBP-1 to -7) are involved in the regulation of cell proliferation and differentiation and may be associated with various metabolic parameters. The aim of our study was to compare levels of IGFs and IGFBPs and the expressions of their genes in children before and after hematopoietic stem cell transplantation (HSCT) to assess their potential as markers of late metabolic complications of HSCT. We also conducted additional comparisons with healthy controls and of correlations of IGF and IGFBP levels with anthropometric and biochemical parameters. We analyzed 19 children treated with HSCT and 21 healthy controls. We found no significant differences in the levels of IGFs and IGFBPs and expressions of their genes before and after HSCT, while IGF and IGFBP levels were significantly lower in children treated with HSCT compared with controls. We conclude that our results did not reveal significant differences between the levels of IGFs and IGFBPs before and after HSCT, which would make them obvious candidates for markers of late complications of the procedure in children. However, due to the very low number of patients this conclusion must be taken with caution and may be altered by further research.

Mycoses are diseases caused by fungi that involve different parts of the body and can generate dangerous treatment complications. This study aims to analyze fungal infection epidemiology in intensive care units (Pediatric and Cardiac Surgery Intensive Care Units—PCICU) and the Neonatal Intensive Care Unit (NICU) in one large pediatric center in the period 2015–2020 compared with 2005. The year 2005 was randomly selected as a historical time reference to notice possible changes. In 2005 and 2015–2020, 23,334 mycological tests were performed in intensive care units. A total of 4628 tests (19.8%) were performed in the intensive care units. Microbiological diagnostics involved mycological and serological testing. Of the 458 children hospitalized in the NICU, positive results in the mycological tests in the studied years were found in 21–27% of the children and out of 1056 PCICU patients, positive results were noticed in 18–29%. In both departments, the main detected pathogen was Candida albicans which is comparable with data published in other centers. Our experience indicates that blood cultures as well as the detection of antifungal antibodies do not add important information to mycological diagnostics. For the years of observation, only a few positive results were detected, even in patients with invasive fungal diseases. To our knowledge, this is one of a few similar studies over recent years and it provides contemporary reports of mycoses in pediatric ICU patients.

Insulin-like growth factors (IGFs) and insulin-like growth-factor-binding proteins (IGFBPs) regulate cell proliferation and differentiation and may be of importance in obesity development. The aim of the study was to analyze the expression of chosen IGF-axis genes and the concentration of their protein products in 28 obese children (OB) and 34 healthy control (HC), and their correlation with essential parameters associated with childhood obesity. The gene expression of IGFBP7 was higher, and the expression of IGF2 and IGFBP1 genes was lower in the OB. The expression of IGFBP6 tended to be lower in OB. IGFBP4 concentration was significantly higher, and IGFBP3 tended to be higher in the OB compared to the HC, while IGFBP1, IGFBP2, and IGFBP6 were significantly lower, and IGFBP7 tended to be lower in OB. We found numerous correlations between IGFs and IGFBP concentration and obesity metabolic parameters. IGFBP6 correlated positively with apelin, cholecystokinin, glucagone-like peptide-1, and leptin receptor. These peptides were also significantly lower in obese children in our study. The biological role of decreased levels of IGFBP6 in obese children needs further investigation.

The occurrence of childhood obesity is influenced by both genetic and epigenetic factors. FTO (FTO alpha-ketoglutarate dependent dioxygenase) is a gene of well-established connection with adiposity, while a protooncogene PLAG1 (PLAG1 zinc finger) has been only recently linked to this condition. We performed a cross-sectional study on a cohort of 16 obese (aged 6.6–17.7) and 10 healthy (aged 11.4–16.9) children. The aim was to evaluate the relationship between methylation and expression of the aforementioned genes and the presence of obesity as well as alterations in anthropometric measurements (including waist circumference (WC), body fat (BF_kg) and body fat percent (BF_%)), metabolic parameters (lipid profile, blood glucose and insulin levels, presence of insulin resistance) and blood pressure. Expression and methylation were measured in peripheral blood mononuclear cells using a microarray technique and a method based on restriction enzymes, respectively. Multiple regression models were constructed to adjust for the possible influence of age and sex on the investigated associations. We showed significantly increased expression of the FTO gene in obese children and in patients with documented insulin resistance. Higher FTO expression was also associated with an increase in WC, BF_kg, and BF_% as well as higher fasting concentration of free fatty acids (FFA). FTO methylation correlated positively with WC and BF_kg. Increase in PLAG1 expression was associated with higher BF%. Our results indicate that the FTO gene is likely to play an important role in the development of childhood adiposity together with coexisting impairment of glucose-lipid metabolism.

Application of mesenchymal stem cells (MSC) enables a novel approach to the therapy of graft- vs-host disease (GVHD) after hematopoietic stem cell transplantation. Herein we present our preliminary experience with the use of allogeneic bone marrow‒derived MSC in 9 pediatric patients after hematopoietic transplantation complicated by severe acute or chronic GVHD (aGVHD, cGVHD) resistant to steroids and second-line immunosuppressants. The MSC therapy was applied concurrently with immunosuppressive treatment in 5 patients as a single infusion, in four patients as 2-6 infusions. The median dose of cells per infusion was 1.9 × 106/kg of recipient body weight (range, 0.1–6.5 × 106/kg). The median quantity of cells applied to patients was 1.2 × 106/kg (range, 0.2–30.9 × 106/kg). We did not observe any adverse symptoms of MSC therapy. Overall, partial, or complete remission (PR and CR, respectively) was obtained in 56% of patients after the first MSC infusions, and 44% after completing therapy. In those with skin involvement 50% achieved permanent CR, 38% in those with gastrointestinal manifestations, and 33% in those with liver GVHD. Three patients with overlap syndrome had amelioration, but none had permanent remission. Long-term improvement after consecutive MSC doses was observed in 3 patients. In the 4- to 8-year follow-up, 3 patients are alive and 2 have attained permanent remission. Six patients died during follow-up: 4 with aGVHD and 2 with infectous complications. Co-treatment of streoid-resistant GVHD with MSC and conventional immunosuppression can improve the outcome, although therapy regimens remain to be established.

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.

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 (p0.05) 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.

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.

The aim of the study was the evaluation of safety and efficacy of vaccination in children after stem cell transplantation.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.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.(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.

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.

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.

Hemophagocytic syndrome (HS) is a rare but life-threatening disease caused by inappropriate activation of T-lymphocytes and histiocytes, hipercytokinemia and hemophagocytosis. The most common symptoms are fever, hepatosplenomegaly, unspecific neurological abnormalities, pancytopenia, coagulopathy, hiperferritinemia and lipid abnormalities. HS is classified into two forms: primary, inherited (Familial Hamophagocytic Lymphohistiocytosis--FHL) and secondary (associated with infection, malignancy, autoimmune disease). In spite of the fact that diagnostic guidelines are available it often remains unrecognised. Prognosis of HS depends on the form of disease and in case of secondary HS on the underlying disease. Development of the treatment protocols (HLH-94, HLH-2004) which combine immunochemiotherapy with hematopoietic stem cell transplantation has strongly improved prognosis in HS especially in the primary form. Three-year overall survival for children with HS is now over 50%. Early diagnosis and appropriate therapy is crucial for effectiveness of the treatment. Popularisation of the knowledge about the syndrome, diagnostic guidelines and treatment protocols can contribute to more frequent appropriate recognition of HS and to improvement of the treatment results.

The aim of the study was to evaluate the efficacy of hepatitis B prophylaxis in children with acute lymphoblastic leukemia (ALL) and to try to determine the optimal procedure of protection against the infection. The retrospective analysis included 229 patients with ALL divided into three groups depending on the type of anti-HBV prophylaxis. The group 1 (1990-91, 38 patients) received only sporadically passive prophylaxis, in the group 2 (1992-94, 55 patients) passive prophylaxis was regular, and the patients of the group 3 (1995-2001, 138 children) received complete active and passive prophylaxis. Among vaccinated children three subgroups were additionally distinguished: subgroup a--vaccination was completed before the disease, subgroup b--the cycle of vaccination began before and continued during the therapy, subgroup c--the whole cycle of vaccination was performed during the ALL treatment. The efficacy of the prophylaxis was evaluated taking into account the incidence of hepatitis B and the level of anti-HBs antibodies in vaccinated children. Additionally the incidence of hepatitis C was assessed to evaluate the role of unspecific prophylaxis. The incidence of hepatitis B in the group 1, 2, and 3 was: 57.9%, 23.6%, and 0.76%, respectively, and the incidence of hepatitis C: 44.7%, 36.4%, and 5.9%, respectively. The percent of the failure of active prophylaxis in the subgroup a, b, and c was: 29%, 53%, and 93%, respectively. In spite of the reduction of exposure to the infection (unspecific prophylaxis), the role of specific prophylaxis is essential. The program of passive and active prophylaxis used by us is efficient in preventing hepatitis B in children with ALL. However, during the intensive chemotherapy only passive prophylaxis should be used with postponement of the vaccination because of very low response to the vaccination applied in this phase of treatment. Regular control of anti-HBs antibodies' level is essential in all patients with leukemia even in those with initially high level of antibodies.