80 research outputs found

    PICU mortality of children with cancer admitted to pediatric intensive care unit : a systematic review and meta-analysis

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    Background: Outcomes for children diagnosed with cancer have improved dramatically over the past 20 years. However, although 40% of pediatric cancer patients require at least one intensive care admission throughout their disease course, PICU outcomes and resource utilization by this population have not been rigorously studied in this specific group. Methods: Using a systematic strategy, we searched Medline, Embase, and CINAHL databases for articles describing PICU mortality of pediatric cancer patients admitted to PICU. Two investigators independently applied eligibility criteria, assessed data quality, and extracted data. We pooled PICU mortality estimates using random-effects models and examined mortality trends over time using meta-regression models. Results: Out of 1218 identified manuscripts, 31 studies were included covering 16,853 PICU admissions with the majority being retrospective in nature. Overall pooled weighted mortality was 27.8% (95% confidence interval (CI), 23.7-31.9%). Mortality decreased slightly over time when post-operative patients were excluded. The use of mechanical ventilation (odds ratio (OR): 18.49 [95% CI 13.79-24.78], p < 0.001), inotropic support (OR: 14.05 [95% CI 9.16-21.57], p < 0.001), or continuous renal replacement therapy (OR: 3.24 [95% CI 1.31-8.04], p = 0.01) was significantly associated with PICU mortality. Conclusions: PICU mortality rates of pediatric cancer patients are far higher when compared to current mortality rates of the general PICU population. PICU mortality has remained relatively unchanged over the past decades, a slight decrease was only seen when post-operative patients were excluded. This compared infavorably with the improved mortality seen in adults with cancer admitted to ICU, where research-led improvements have led to the paradigm of unlimited, aggressive ICU management without any limitations on resuscitations status, for a time-limited trial

    Design strategies for promoting young children’s physical activity: A playscapes perspective

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    This paper develops a set of design strategies for promoting young children’s physical activity. These strategies are developed by taking the design perspective of Playscapes as a starting point. Playscapes suggests that three play qualities are key in promoting young children’s physical activity: free, bodily, and dispersed play. We present two field studies in a pediatric oncology center, in which we observed how these play qualities were reflected in children’s interactions with two Playscape designs: Stickz, a collection of branch-shaped objects, were placed in a semi-public waiting area; Fizzy, a self-propelled robotic ball, was introduced to patient rooms. Free play was analyzed according to the diversity of play activities, bodily play according to the diversity and exertion level of bodily movements, and dispersed play according to the floor area covered. Based on the findings, we discuss how Fizzy and Stickz contributed to each play quality, and derive a set of design strategies that can be applied in different contexts to stimulate young children’s physical activity. With these strategies, Playscapes offers a concrete alternative to existing approaches, supporting designers in directing interactions towards physical activity while leaving room for children’s unstructured and spontaneous play

    Clinical and Molecular Characteristics and Outcome of Cystic Partially Differentiated Nephroblastoma and Cystic Nephroma: A Narrative Review of the Literature

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    In children presenting with a predominantly cystic renal tumor, the most likely diagnoses include cystic partially differentiated nephroblastoma (CPDN) and cystic nephroma (CN). Both entities are rare and limited information on the clinical and molecular characteristics, treatment, and outcome is available since large cohort studies are lacking. We performed an extensive literature review, in which we identified 113 CPDN and 167 CN. The median age at presentation for CPDN and CN was 12 months (range: 3 weeks–4 years) and 16 months (prenatal diagnosis–16 years), respectively. No patients presented with metastatic disease. Bilateral disease occurred in both entities. Surgery was the main treatment for both. Two/113 CPDN patients and 26/167 CN patients had previous, concomitant, or subsequent other tumors. Unlike CPDN, CN was strongly associated with somatic (n = 27/29) and germline (n = 12/12) DICER1-mutations. Four CPDN patients and one CN patient relapsed. Death was reported in six/103 patients with CPDN and six/118 CN patients, none directly due to disease. In conclusion, children with CPDN and CN are young, do not present with metastases, and have an excellent outcome. Awareness of concomitant or subsequent tumors and genetic testing is important. International registration of cystic renal tumor cohorts is required to enable a better understanding of clinical and genetic characteristics

    Long-term nephrotoxicity in irradiated pediatric kidney tumor survivors: A systematic review

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    OBJECTIVE: Nephrotoxicity can occur as a side effect after treatment for kidney tumor in childhood. The use of radiotherapy (RT) has a potential additional effect. METHODS: A systematic electronic literature search that combined childhood kidney cancer with different treatments and nephrotoxicity terms was performed in EMBASE. Studies were included based on the reporting of nephrotoxicity occurrence after treatment for kidney tumor during pediatric age, with 75% of participants being under the age of 25 years at the time of diagnosis, and having been treated with any type of kidney surgery, chemotherapy, and/or RT. RESULTS: A pooled analysis did not show significant difference in estimated glomerular filtration rate between the group of patients who received RT compared with the group treated without RT (SMD -0.11 [95% CI -1.07-0.84] p = .733). CONCLUSION: The current literature suggests that the use of RT does not have a significant impact on the decline of kidney function as independent factor

    The contribution of surgical clips for optimizing highly-conformal image-guided flank irradiation in pediatric renal tumors: a single center experience

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    Background and aims: Two-opposing photon beams are considered standard of care for flank irradiation in pediatric patients with renal tumors. Nowadays, Image-Guided Radiotherapy (IGRT) techniques allow high-precision dose delivery to complex flank target volumes taking into account postoperative organ shifts and tumor bed motion. This study examines the contribution of a lateral and superior surgical clip on flank target volume delineation intended for IGRT. Methods: Between 01-2015 and 09-2019, 30/162 newly-diagnosed pediatric patients with renal tumors, lateral/superior surgical clips (n = 30/30) and available 4D-CT-scans (n = 27/30), underwent postoperative flank irradiation. The lateral and superior clip, as respective markers for the lateral tumor extension and intrafraction motion, were analyzed. The positive and negative values depict the lateral/dorsal/cranial or the medial/ventral/caudal direction, respectively. Planning target volumes (PTV) were generated based on lateral clips (PTV latclip), superior clips with 4D-CT technology (PTV supclip), and both clips combined (PTV combined), and compared to an approach without clips (PTV noclip). Results: Indicated by clips, the mean lateral tumor bed extension along the posterior wall was 74° (range: 50°–93°), while mean intrafraction motion was +1.2 mm (range: −1.8/+4.8 mm), +0.6 mm (range: +0.6/+4.9 mm), −0.3 mm (range: −3.8/+0.7 mm) in craniocaudal, ventrodorsal, mediolateral direction, respectively. The median PTV noclip (556 mL) was statistically different from the median PTV latclip (454 mL, p = <0.01), median PTV supclip (373 mL, p = <0.01) and median PTV combined (348 mL p = <0.01). Conclusion: In pediatric patients with renal tumors, surgical clips at the lateral and superior border of the tumor bed can optimize flank target volume delineation and, consequently, reduce the normal tissue volume receiving high-dose irradiation when IGRT techniques are applied

    Outcome of Stage IV Completely Necrotic Wilms Tumour and Local Stage III Treated According to the SIOP 2001 Protocol

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    Objective: Wilms tumour (WT) patients with a localised completely necrotic nephroblastoma after preoperative chemotherapy are a favourable outcome group. Since the introduction of the SIOP 2001 protocol, the SIOP– Renal Tumour Study Group (SIOP–RTSG) has omitted radiotherapy for such patients with low-risk, local stage III in an attempt to reduce treatment burden. However, for metastatic patients with local stage III, completely necrotic WT, the recommendations led to ambiguous use. The purpose of this descriptive study is to demonstrate the outcomes of patients with metastatic, completely necrotic and local stage III WT in relation to the application of radiotherapy or not. Methods and materials: all metastatic patients with local stage III, completely necrotic WT after 6 weeks of preoperative chemotherapy who were registered in the SIOP 2001 study were included in this analysis. The pattern of recurrence according to the usage of radiation treatment and 5 year event-free survival (EFS) and overall survival (OS) was analysed. Results: seven hundred and three metastatic WT patients were registered in the SIOP 2001 database. Of them, 47 patients had a completely necrotic, local stage III WT: 45 lung metastases (11 combined localisations), 1 liver/peritoneal, and 1 tumour thrombus in the renal vein and the inferior vena cava with bilateral pulmonary arterial embolism. Abdominal radiotherapy was administered in 29 patients (62%; 29 flank/abdominal irradiation and 9 combined with lung irradiation). Eighteen patients did not receive radiotherapy. Median follow-up was 6.6 years (range 1–151 months). Two of the 47 patients (4%) developed disease recurrence in the lung (one combined with abdominal relapse) and eventually died of the disease. Both patients had received abdominal radiotherapy, one of them combined with lung irradiation. Five-year EFS and OS were 95% and 95%, respectively. Conclusions: the outcome of patients with stage IV, local stage III, completely necrotic Wilms tumours is excellent. Our results suggest that abdominal irradiation in this patient category may not be of added value in first-line treatment, consistent with the current recommendation in the SIOP–RTSG 2016 UMBRELLA protocol

    TIMELESS Forms a Complex with PARP1 Distinct from Its Complex with TIPIN and Plays a Role in the DNA Damage Response

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    SummaryPARP1 is the main sensor of single- and double-strand breaks in DNA and, in building chains of poly(ADP-ribose), promotes the recruitment of many downstream signaling and effector proteins involved in the DNA damage response (DDR). We show a robust physical interaction between PARP1 and the replication fork protein TIMELESS, distinct from the known TIMELESS-TIPIN complex, which activates the intra-S phase checkpoint. TIMELESS recruitment to laser-induced sites of DNA damage is dependent on its binding to PARP1, but not PARP1 activity. We also find that the PARP1-TIMELESS complex contains a number of established PARP1 substrates, and TIMELESS mutants unable to bind PARP1 are impaired in their ability to bind PARP1 substrates. Further, PARP1 binding to certain substrates and their recruitment to DNA damage lesions is impaired by TIMELESS knockdown, and TIMELESS silencing significantly impairs DNA double-strand break repair. We hypothesize that TIMELESS cooperates in the PARP1-mediated DDR

    Surgical Outcome of Children with a Malignant Liver Tumour in The Netherlands:A Retrospective Consecutive Cohort Study

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    INTRODUCTION: Six to eight children are diagnosed with a malignant liver tumour yearly in the Netherlands. The majority of these tumours are hepatoblastoma (HB) and hepatocellular carcinoma (HCC), for which radical resection, often in combination with chemotherapy, is the only curative treatment option. We investigated the surgical outcome of children with a malignant liver tumour in a consecutive cohort in the Netherlands. METHODS: In this nationwide, retrospective observational study, all patients (age &lt; 18 years) diagnosed with a malignant liver tumour, who underwent partial liver resection or orthotopic liver transplantation (OLT) between January 2014 and April 2021, were included. Children with a malignant liver tumour who were not eligible for surgery were excluded from the analysis. Data regarding tumour characteristics, diagnostics, treatment, complications and survival were collected. Outcomes included major complications (Clavien-Dindo ≄ 3a) within 90 days and disease-free survival. The results of the HB group were compared to those of a historical HB cohort. RESULTS: Twenty-six children were analysed, of whom fourteen (54%) with HB (median age 21.5 months), ten (38%) with HCC (median age 140 months) and one with sarcoma and a CNSET. Thirteen children with HB (93%) and three children with HCC (30%) received neoadjuvant chemotherapy. Partial hepatic resection was possible in 19 patients (12 HB, 6 HCC, and 1 sarcoma), whilst 7 children required OLT (2 HB, 4 HCC, and 1 CNSET). Radical resection (R0, margin ≄ 1.0 mm) was obtained in 24 out of 26 patients, with recurrence only in the patient with CNSET. The mean follow-up was 39.7 months (HB 40 months, HCC 40 months). Major complications occurred in 9 out of 26 patients (35% in all, 4 of 14, 29% for HB). There was no 30- or 90-day mortality, with disease-free survival after surgery of 100% for HB and 80% for HCC, respectively. Results showed a tendency towards a better outcome compared to the historic cohort, but numbers were too small to reach significance. CONCLUSION: Survival after surgical treatment for malignant liver tumours in the Netherlands is excellent. Severe surgical complications arise in one-third of patients, but most resolve without long-term sequelae and have no impact on long-term survival

    Paediatric metanephric tumours: a clinicopathological and molecular characterisation

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    To characterize metanephric tumours in children, we performed a literature review investigating paediatric metanephric adenomas (MA), metanephric stromal tumours (MST) and metanephric adenofibromas (MAF). Including two patients from our own institution (MA, MAF), 110 individual cases (41 MA, 20 MAF, 49 MST) were identified. Additionally, fifteen composite tumours were identified, with areas of MA/MAF and Wilms tumour (WT) or papillary carcinoma. No distinct clinical or radiological features could be defined. In pure metanephric tumours, histologically proven distant metastases were reported once (MA), relapse was reported once (MST) and one tumour-related death occurred (MST). Somatic BRAF-V600E mutations were tested in 15 cases, and identified in 3/6 MA, 3/3 MAF, and 6/6 MST. In our institution the MA harboured a somatic KRAS-G12R mutation. Overall, paediatric metanephric tumours are difficult to discriminate from other renal tumours at presentation, behave relatively benign, and the occurrence of composite tumours warrants analysis of underlying (genetic) pathways

    Daily life participation in childhood chronic disease: A qualitative study on the child's and parent's perspective

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    Objective To understand how a child with a stable chronic disease and his/her parents shape his/her daily life participation, we assessed: (1) the parents' goals regarding the child's daily life participation, (2) parental strategies regarding the child's participation and () how children and their parents interrelate when their goals regarding participation are not aligned. Methods This was a qualitative study design using a general inductive approach. Families of children 8-19 years with a stable chronic disease (cystic fibrosis, autoimmune disease or postcancer treatment) were recruited from the PROactive study. Simultaneous in-depth interviews were conducted separately with the child and parent(s). Analyses included constant comparison, coding and categorisation. Results Thirty-one of the 57 invited families (54%) participated. We found that parents predominantly focus on securing their child's well-being, using participation as a means to achieve well-being. Moreover, parents used different strategies to either support participation consistent with the child's healthy peers or support participation with a focus on physical well-being. The degree of friction between parents and their child was based on the level of agreement on who takes the lead regarding the child's participation. Conclusions Interestingly, parents described participation as primarily a means to achieve the child's well-being, whereas children described participation as more of a goal in itself. Understanding the child's and parent's perspective can help children, parents and healthcare professionals start a dialogue on participation and establish mutual goals. This may help parents and children find ways to interrelate while allowing the child to develop his/her autonomy
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