The views of parents of children with cancer and pediatric physical therapists on a network for continuity and optimal quality of care for children with cancer: KinderOncoNet.

PURPOSE: Children with cancer require specific therapeutic guidance. Parents prefer physical therapy close to home, while pediatric physical therapists (PPTs) working in the community may lack specific knowledge. The aim of this study is to determine the needs of parents of children with cancer and PPTs to inform the design and development of a care network, named "KinderOncoNet." METHODS: We explored the perspectives and needs of parents of children with cancer and PPTs in the community, and we investigated the added value that KinderOncoNet could offer. We used an iterative process; data collection consisted of (1) gathering information from parents of children with cancer and PPTs through a survey and (2) co-creation sessions with stakeholders. RESULTS: In total, 98 parents and 177 PPTs participated in the survey. Parents (97%) and PPTs (93%) indicated that the care network would bring added value. All but one parent stressed the importance of a local PPT being aware of both the condition and the side and late effects of oncological treatment. Moreover, 40% of PPTs thought they do not have sufficient knowledge to provide high-quality therapy and that they would embrace opportunities for education. Through the co-creation sessions, a prototype of the care network was conceptualized. CONCLUSION: KinderOncoNet can contribute to the continuity and quality of physiotherapy care for children with cancer during and after the oncological treatment. Such a network would allow for sharing knowledge, developing skills, and improving accessibility and communication in the Netherlands.

High-quality care for all children with cancer.

BACKGROUND: Providing high-quality care for children with cancer could improve treatment outcomes, survival and quality of life of the children and parents. The aim of this study is to select high-quality care recommendations for all children with cancer based on literature and consensus for future development of quality indicators. MATERIALS AND METHODS: We performed an extensive search in databases for scientific literature and in websites of international health care and guideline development organizations to create an inventory of recommendations for the care for all children with cancer. The RAND modified Delphi method was used to grade and select recommendations for high-quality care. RESULTS: Our search resulted in a list of 131 recommendations on care for all children with cancer. The expert panel graded, discussed and prioritized these recommendations. Analysis of these ratings resulted ultimately in a list of 109 high-quality care recommendations for all children with cancer, including 31 prioritized recommendations. CONCLUSIONS: This study defines a set of high-quality care recommendations based on literature and consensus. These recommendations provide a basis for the development of a comprehensive set of quality indicators to evaluate care in paediatric oncology.

Management and outcome in 32 neonates with thrombotic events.

Objective. To determine the incidence, management, complications, and outcome in neonates with thrombotic events. Study Design. We performed a retrospective study of all neonates with thrombotic events admitted to our neonatal intensive care unit from January 2004 to July 2010. Results. Thrombotic events were identified in 32 of 4734 neonates (0.7%). Seven neonates were managed expectantly and 25 neonates received anticoagulant treatment. Complete resolution of the clot within 3 months of age was found in 68% (17/25) of the treated and in 86% (6/7) of the nontreated neonates. Major complications due to anticoagulant therapy occurred in 3/25 cases (12%) and included severe hemorrhage (n = 2) and abscess at the injection site (n = 1). Conclusion. Complete or partial clot resolution in neonatal thrombosis occurred in both the treated group and nontreated group. Randomized controlled trials are warranted to determine the optimal management in neonatal thrombosis.

Severe hemorrhage after low-molecular-weight heparin treatment in a preterm neonate.

Thromboembolic events in preterm neonates are increasingly being diagnosed due to the increasing use of umbilical catheters and central venous catheters. Whether thromboembolic events should be treated routinely with low-molecular-weight heparin (LMWH) is controversial and the optimal management is still not clear due to the lack of randomized controlled trials. Most importantly, knowledge about the safety of treatment with LMWH in neonates with thromboembolic events is very limited. We present a case of severe hemorrhage in a preterm neonate after LMWH treatment and summarize the scarce data reported in the literature.

High burden of late effects after haematopoietic stem cell transplantation in childhood: a single-centre study.

The aim of our study was to assess the cumulative incidence and severity ('burden') of late effects in a single-centre cohort of childhood haematopoietic stem cell transplantation (HSCT) survivors, at least 2 years after transplantation. The presence and severity of late effects in each survivor was documented according to the Common Terminology Criteria for Adverse Events (version 3.0). The burden of late effects was graded from mild to disabling/life-threatening. Risk factors for a high burden of late effects were assessed by univariate and multivariate logistic regression analyses. Among 162 survivors of HSCT seen in our late effects outpatient clinic, cumulative incidence of late effects was 93.2% after a median follow-up time of 7.2 years (range 2.0-21.0 years) after HSCT. The burden of late effects was mild, moderate, severe and disabling in 28, 41, 24 and 1% of survivors respectively. Risk factors for a severe or disabling burden of late effects were older age at HSCT (P for trend <0.001) and a conditioning regimen including irradiation OR 2.2, 95% CI 1.1-4.7, P=0.03). In conclusion, a high burden of late effects is found in childhood HSCT survivors after a median follow-up of only 7 years.

Sudden death due to pulmonary embolism as presenting symptom of renal tumors.

In 4-6% of patients with renal tumors in children intravascular infiltration is found. Tumor emboli are even rarer, and sudden death as presenting symptom has only been described at presentation in Wilms tumor (WT) in six cases so far. This report describes two recent cases of sudden death in patients with renal tumors in which a fatal pulmonary embolus was the first presentation.

CFTR is functionally active in GnRH-expressing GT1-7 hypothalamic neurons.

We have demonstrated the expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, mRNA, and protein within the rat and human brains, in areas regulating sexual differentiation and function. We have found that GT1-7, a gonadotropin-releasing hormone (GnRH)-secreting hypothalamic neuronal cell line, expresses the CFTR gene, mRNA, and protein and cAMP-dependent (36)Cl efflux. A linear 7-pS Cl- conductance, which is stimulated by ATP and cAMP analogs and inhibited by glibenclamide, consistent with CFTR activity, has been identified in GT1-7 cells. Antisense oligo(dN) generated against exon 10 of the CFTR gene transcript (mRNA) inhibit GnRH secretion into media [312 +/- 73, 850 +/- 150, 963 +/- 304, and 912 +/- 74 pg GnRH/4 x 10(6) cells for antisense, sense, missense, and no oligo(dN), respectively; P < 0. 029 for antisense oligo(dN)-treated vs. normal cells]. No changes in intracellular synthesis of GnRH were noted [1,400 +/- 371 and 1,395 +/- 384 pg GnRH/4 x 10(6) cells for antisense and sense oligo(dN), respectively]. Antisense oligo(dN), but not sense or missense oligo(dN), inhibited cAMP-dependent 36Cl efflux. The expression of CFTR protein, detected by Western blotting, was also inhibited 68% by preincubation of cells with antisense oligo(dN). GT1-7 hypothalamic neurons express the CFTR gene, mRNA, and protein, which modulate neurosecretion. Abnormal neuropeptide vesicle trafficking by mutant CFTR may help to explain some of the diverse manifestations of cystic fibrosis.

Enhanced efficiency of lactosylated poly-L-lysine-mediated gene transfer into cystic fibrosis airway epithelial cells.

Lactosylated poly-L-lysine is a nonviral vector that transfers genes into airway epithelial cells, including those from individuals with cystic fibrosis (CF). Substitution of 40% of the epsilon-amino groups of poly-L-lysine with lactosyl residues not only provided a ligand for receptor-mediated endocytosis, but also reduced the toxicity when compared with nonsubstituted poly-L-lysine. Lactosylated poly-L-lysine/pCMVLuc complex is not toxic to cells in amounts that gave the maximum gene expression. The level of gene expression was regulated by using different combinations of chloroquine, glycerol, and E5CA peptide. Using cultured CF cells, chloroquine, combined with E5CA peptide, increased the transfer of the pCMVLuc/ lactosylated poly-L-lysine complex 10,000-fold compared with transfer without additives. In many systems, a high efficiency is of paramount importance and the enhancing agents can be used to modulate the expression of the gene. For example, transfer of pCMVLacZ/lactosylated poly-L-lysine complexes with chloroquine added to the transfection medium gave only 20% transfection efficiency of the reporter gene. However, when chloroquine was combined with glycerol, the efficiency was increased to 90%, thus approaching that reported with viral vectors. This highly efficient vector may be of great value for the future development of gene transfer systems.

High-efficiency transfer of cystic fibrosis transmembrane conductance regulator cDNA into cystic fibrosis airway cells in culture using lactosylated polylysine as a vector.

To find more efficient vectors for the transfer of CFTR cDNA, lactosylated polylysine was explored for transfer into airway epithelial cells in primary culture. The efficacy and high efficiency of transfection were shown by several criteria: expression of both mRNA and protein for CFTR and the functional correction of the Cl- channel activity. Using specific combinations of agents to enhance the transfection, an efficiency of 90% was obtained as detected by in situ hybridization with digoxigenin-labeled probes generated against exon 14 of CFTR. The highest efficiency was observed by adding E5CA peptide (10 microg) and 5% glycerol to the transfection mixture. The degree of transfection could be controlled by the enhancing agents, thus modulating the efficiency of transfection. The highest level of transfection efficiency is equivalent to that reported for viral vectors. None of the agents or their combinations in the concentrations used were cytotoxic to the primary cells. Antibody pAb3145 was used to detect the expression of the CFTR protein in the cells. When an N-terminal GFP-CFTR fusion gene was used to transfect the CF cells a functional correction of the CFTR Cl- channel was detected by patch-clamp electrophysiology. The high efficiency of CFTR gene transfer with lactosylated polylysine leads to the conclusion that lactosylated polylysine is a promising vector to transfer the CFTR gene into human airway cells in culture.

Gluconoylated and glycosylated polylysines as vectors for gene transfer into cystic fibrosis airway epithelial cells.

To provide an alternative to viral vectors for the transfer of genes into airway epithelial cells in cystic fibrosis (CF), a novel set of substituted polylysines were employed. Polylysine was partially neutralized by blocking a number of positively charged residues with gluconoyl groups. In addition, polylysine was substituted with sugar residues on a specified number of amino groups. Using the gluconoylated polylysine as vector, the pCMVLuc plasmid gave high expression of the reporter gene luciferase in immortalized CF/T43 cells. The luciferase activity was 75-fold greater in the presence of 100 microM chloroquine. Luciferase gene expression persisted at high levels for up to at least 120 hr following transfection. Glycosylated polylysines/pCMVLuc complexes were compared to the gluconoylated polylysine/pCMVLuc complex and beta-Gal-, alpha-Glc-, and Lac-substituted polylysines gave 320%, 300%, and 290%, respectively, higher expression of the reporter gene luciferase. Luciferase expression ranged from 35 to 2 ng of luciferase per milligram of cell protein in the order: beta-Gal = alpha-Glc = Lac > alpha-Gal = Rha = Man > beta-GalNAc > alpha-GalNAc = alpha-Fuc, suggesting that the transfection efficiency is sugar dependent. Most importantly, in primary cultures of both CF and non-CF airway epithelial cells grown from tracheal tissue explants, lactosylated polylysine gave uniformly high expression of luciferase. The glycosylated polylysines provide an attractive nonviral approach for the transfer of genes into airway epithelial cells.