Sullivan R.,Health Integrated |
Kowalczyk J.R.,Medical University of Lublin |
Agarwal B.,B J Wadia Hospital for Children |
Ladenstein R.,St Anna Childrens Hospital |
And 12 more authors.
The Lancet Oncology | Year: 2013
Childhood cancer is a major global health issue. Every year, almost 100 000 children die from cancer before the age of 15 years, more than 90% of them in resource-limited countries. Here, we review the key policy issues for the delivery of better care, research, and education of professionals and patients. We present a key list of time-limited proposals focusing on change to health systems and research and development. These include sector and system reforms to make care affordable to all, policies to promote growth of civil society around both cancer and Millennium Development Goals, major improvements to public health services (particularly the introduction of national cancer plans), improved career development, and increased remuneration of specialist health-care workers and government support for childhood cancer registries. Research and development proposals focus on sustainable funding, the establishment of more research networks, and clinical research specifically targeted at the needs of low-income and middle-income countries. Finally, we present proposals to address the need for clinical trial innovation, the complex dichotomy of regulations, and the threats to the availability of data for childhood cancers. © 2013 Elsevier Ltd.
Trottestam H.,Karolinska University Hospital |
Horne A.,Karolinska University Hospital |
Arico M.,Azienda Ospedaliero Universitaria A. Meyer |
Egeler R.M.,Leiden University |
And 7 more authors.
Blood | Year: 2011
Hemophagocytic lymphohistiocytosis (HLH) used to have a dismal prognosis.We report the final results of HLH-94, the largest prospective diagnostic/therapeutic HLH study so far. The treatment includes immunosuppressive and cytotoxic therapy aiming at clinical remission, followed by HSCT in patients with familial, persistent, or recurrent disease. Altogether, 249 patients fulfilled inclusion criteria and started HLH-94 therapy (July 1994-December 2003); 227 (91%) were followed-up for ≥ 5 years. At 6.2 years median follow-up, estimated 5-year probability of survival was 54% ± 6%. Seventy-two patients (29%) died before HSCT, 64 within 1 year, 97% of whom had active disease. In 124 patients who underwent HSCT, 5-year survival was 66 ± 8%; tendency to increased survival (P = .064) in patients with nonactive disease at HSCT. Patients with familial disease had a 5-year survival of 50% ± 13%; none survived without HSCT. Patients deceased during the first 2 months more often had jaundice, edema, and elevated creatinine. Forty-nine patients (20%) were alive without signs of HLH activity and off-therapy > 1-year without HSCT; they presented at older age (P<.001), weremoreoften female (P=.011), and less often had CNS disease (P < .001) or hepatomegaly (P = .007). To conclude, HLH-94 chemoimmunotherapy has considerably improved outcome in HLH. Collaborative efforts are needed to further reduce early mortality, HSCT-related mortality, and neurologic late effects. © 2011 by The American Society of Hematology.
Pulsipher M.A.,University of Utah |
Peters C.,St Anna Childrens Hospital |
Pui C.-H.,St Jude Childrens Research Hospital
Biology of Blood and Marrow Transplantation | Year: 2011
Because survival with both chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT) approaches to high-risk pediatric acute lymphoblastic leukemia (ALL) generally improves through the years, regular comparisons of outcomes with either approach for a given indication are needed to decide when HSCT is indicated. Improvements in risk classification are allowing clinicians to identify patients at high risk for relapse early in their course of therapy. Whether patients defined as high risk by new methods will benefit from HSCT requires careful testing. Standardization and improvement of transplant approaches has led to equivalent survival outcomes with matched sibling and well-matched unrelated donors; however, survival using mismatched and haploidentical donors is generally worse. Trials comparing chemotherapy and HSCT must obtain sufficient data about therapy and stratify the analysis to assess the outcomes of best-chemotherapy with best-HSCT approaches. © 2011 American Society for Blood and Marrow Transplantation.
Gadermayr M.,University of Salzburg |
Uhl A.,University of Salzburg |
Vecsei A.,St Anna Childrens Hospital
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2013
Fourier based feature extraction is a common and powerful technique used in texture classification. In case of endoscopic imaging, often significant barrel-type distortions affect the feature extraction. Although images can be rectified using distortion correction techniques, in previous work feature extraction proved to suffer not just from geometric distortions, but also from effects within distortion correction. Distortion correction in combination with Fourier features has not been investigated so far. We introduce and evaluate three strategies to partially or completely compensate the geometric distortion in combination with Fourier features. With two methods, the interpolation within distortion correction can be omitted which should lead to a benefit in classification. Instead of making a general statement, we distinguish between certain frequencies and identify the positive and the negative aspects of the strategies. © 2013 Springer-Verlag.
Ronceray L.,Childrens Cancer Research Institute |
Potschger U.,Childrens Cancer Research Institute |
Janka G.,University of Hamburg |
Gadner H.,Childrens Cancer Research Institute |
And 2 more authors.
Journal of Pediatrics | Year: 2012
Objectives: To assess the effect of pulmonary involvement on the course and outcome of multisystem Langerhans cell histiocytosis (MS-LCH) in children. Study design: We conducted a retrospective analysis of 420 consecutive patients with MS-LCH. In this analysis, the term "risk organs" is defined as involvement of the liver, spleen, and/or hematopoietic system. The effect of pulmonary involvement on survival was assessed with multivariate Cox regression with adjustment for risk organs involvement and age. Results: Pulmonary involvement in MS-LCH was present at diagnosis in 102 patients (24%). Of the 318 patients without pulmonary involvement at diagnosis, it developed in 28 within a median of 10 months (range, 1 month-5.5 years). The 5-year overall survival rate in patients without risk organ involvement at diagnosis was 96% in patients without pulmonary involvement and 94% in those with pulmonary involvement. In patients with risk organ involvement at diagnosis, the 5-year overall survival rate was 73% in patients without pulmonary involvement and 65% in patients with pulmonary involvement. In multivariate analysis, pulmonary involvement at diagnosis had no significant impact on survival rats (P =.109, hazard ratio = 1.5). Conclusions: In multivariate analysis, pulmonary involvement was not an independent prognostic variable and should therefore be excluded from the definition of risk organ involvement in MS-LCH. Copyright © 2012 Mosby Inc. All rights reserved.
Hafner M.,St Elisabeth Hospital |
Liedlgruber M.,University of Salzburg |
Uhl A.,University of Salzburg |
Vecsei A.,St Anna Childrens Hospital |
Wrba F.,Medical University of Vienna
Medical Image Analysis | Year: 2012
In this work we propose a novel method to describe local texture properties within color images with the aim of automated classification of endoscopic images. In contrast to comparable Local Binary Patterns operator approaches, where the respective texture operator is almost always applied to each color channel separately, we construct a color vector field from an image. Based on this field the proposed operator computes the similarity between neighboring pixels. The resulting image descriptor is a compact 1D-histogram which we use for a classification using the k-nearest neighbors classifier.To show the usability of this operator we use it to classify magnification-endoscopic images according to the pit pattern classification scheme. Apart from that, we also show that compared to previously proposed operators we are not only able to get competitive classification results in our application scenario, but that the proposed operator is also able to outperform the other methods either in terms of speed, feature compactness, or both. © 2011 Elsevier B.V..
Heitzeneder S.,Childrens Cancer Research Institute |
Seidel M.,St Anna Childrens Hospital |
Forster-Waldl E.,St Anna Childrens Hospital |
Forster-Waldl E.,Medical University of Vienna |
Heitger A.,Childrens Cancer Research Institute
Clinical Immunology | Year: 2012
Mannan-binding lectin (MBL) deficiency has been classified as a commonly occurring immune disorder, affecting approximately 30% of the human population. MBL, being part of the innate immune system, supports the recognition of infectious pathogens by binding to carbohydrate moieties expressed on microorganisms and activates the lectin pathway of the complement system. MBL2 gene polymorphisms are associated with quantitative and qualitative MBL abnormalities in the serum. The clinical impact of MBL deficiency and its association to a wide variety of diseases has been extensively studied. The picture is puzzling as the studies suggest a detrimental or beneficial or no impact of low or high MBL serum levels on disease susceptibility. In this review we attempt to extract what is relevant from the literature and address controversial issues. We finally suggest that a comprehensive understanding of the role of MBL in human diseases requires considering its context-dependency. © 2011 Elsevier Inc.
Paulke-Korinek M.,Medical University of Vienna |
Kollaritsch H.,Medical University of Vienna |
Aberle S.W.,Medical University of Vienna |
Zwazl I.,Medical University of Vienna |
And 3 more authors.
Vaccine | Year: 2013
This hospital based surveillance study evaluates the effects of the rotavirus mass vaccination program, which was initiated in Austria in August 2007. Since then, incidence rates of rotavirus hospitalizations in children <15 years of age have decreased by 70% and 64% in 2010 and 2011 compared to the pre-vaccination era (2001-2005). Incidence rates were highest in children <90 days of age, highlighting the importance of the early start of active rotavirus immunization. In children between 2 and 3.5 years in 2011, who were in the second and third year after vaccination in the universal mass vaccination program, incidence rates remained low suggesting sustained protection after vaccination up to three years. In the years 2010 and 2011, field effectiveness of the vaccines was between 79% and 96%, depending on the assumptions made for children without information on vaccination history. From genotyping an increase of the prevalence of G2P in children with breakthrough infection (disease despite vaccination) can be suspected. The rate of severe adverse events was 1.3-1.5 per 10-5 administered doses of rotavirus vaccines and no death, intussusception or Kawasaki disease was reported in 2010 and 2011 following rotavirus vaccination. © 2013 Elsevier Ltd.
Lawitschka A.,Childrens Cancer Research Institute |
Ball L.,Leiden University |
Peters C.,St Anna Childrens Hospital
Biology of Blood and Marrow Transplantation | Year: 2012
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for many children with life-threatening diseases. One of the most significant long-term complications of transplantation is chronic graft-versus-host disease (cGVHD). Although the rates of cGVHD after HSCT are lower in the pediatric population than in adults, cGVHD remains a significant cause of morbidity and mortality. Medicines used to prevent and treat cGVHD remain unsatisfactory, with protracted use of immune suppression necessary and high rates of first-line treatment failure. Efforts to improve salvage treatment are urgently required. Nonpharmacologic strategies attempt to modulate the cellular inflammation response and possibly allow reduction or cessation of immunosuppressive drugs. Mesenchymal stromal cells (MSC) have been shown invitro to mediate a wide variety of immune responses. MSC have been used in the prophylaxis of acute GVHD (aGVHD) and for the treatment of established steroid refractory aGVHD and, more recently, in the management of cGVHD. Extracorporeal photochemotherapy (ECP) has shown promising efficacy in graft-versus-host disease, and may allow a significant reduction in the use of systemic steroids and other immunosuppressants, reducing long-term morbidity and mortality. The accumulated experience shows ECP to be well tolerated, with no clinically significant side effects. © 2012 American Society for Blood and Marrow Transplantation.
Minkov M.,St Anna Childrens Hospital
Pediatric Drugs | Year: 2011
Langerhans cell histiocytosis (LCH) is a rare (about 35 cases per million children aged 014 years), non-malignant disease characterized by proliferation and accumulation of clonal dendritic cells, extreme clinical heterogeneity, and an unpredictable course. Three large-scale, international, prospective therapeutic studies (LCH-I to III) for multisystem LCH (MS-LCH) have been conducted by the Histiocyte Society since 1991. The cumulative lessons from these studies are summarized in this review. Patients with MS-LCH represent a heterogeneous group with respect to disease severity and outcome, therefore treatment stratification and risk-tailored treatment are mandatory. The risk for mortality can be predicted based on involvement of 'risk organs' (e.g. hematopoietic system, liver, andor spleen) at diagnosis and on response to initial therapy (assessed after 612 weeks of treatment). Thus, patients without involvement of risk organs (low-risk group) are not at risk for mortality but need systemic therapy in order to control the disease activity and avoid reactivations and permanent consequences. Patients with risk organ involvement (risk group) are at risk for mortality, and lack of therapy response defines a subgroup with a particularly dismal prognosis (high-risk group). Those patients in the risk group who respond to therapy and survive are at risk for reactivations and permanent consequences.The LCH-I study compared the efficacy of vinblastine and etoposide, and concluded that they are equivalent single-agent treatments for children with MS-LCH. However, the results of this trial were inferior with respect to response rate at week 6, disease reactivation rate, and sequelae, when compared with historical trials using more intensive regimens. The combination of prednisolone and vinblastine was established as a standard first-line treatment through the LCH-II and LCH-III studies. The regimen consists of one to two 6-week courses (continuous oral corticosteroids 40mgm2day for 4 weeks, tapered over 2 weeks plus weekly vinblastine intravenous push) of initial therapy, followed by a continuation phase (three weekly pulses of oral prednisolone 40mgm2day for 5 days plus a vinblastine injection). The addition of a third drug to the standard combination (etoposide in LCH-II and methotrexate in LCH-III) failed to significantly improve survival in the risk group. The remaining mortality in the risk group is about 20, and up to 40 in the high-risk group. Concerning low-risk MS-LCH, comparison of results of the LCH-II study with historical data suggested that the remaining reactivation rate of about 50 (and possibly permanent consequences) could be reduced by prolongation of the total treatment duration. To study this hypothesis, in the low-risk group of the LCH-III study standard maintenance therapy was randomly given for a total treatment duration of 6 and 12 months. Unpublished preliminary data from this recently closed trial suggested that prolongation of the treatment duration may significantly improve reactivation-free survival.In summary, several studies have shown that systemic therapy is indicated for all patients with MS-LCH. A standard two-drug regimen consisting of an initial 'intensive' phase for 612 weeks, followed by a less intensive 'maintenance phase' for a total treatment duration of at least 12 months is recommended for patients treated outside of clinical trials. Non-responders, particularly those with progressive disease in risk organs, are eligible for experimental salvage approaches. Remaining questions will be addressed in the upcoming LCH-IV trial, which is in the process of intensive preparation. © 2011 Adis Data Information BV. All rights reserved.