Oncogenomics and Pediatric Health

Topic Information

Dear Colleagues,

This Topic will report on developments, challenges, and opportunities in the diagnosis and treatment of cancer and blood diseases in children in developed and developing countries. Genome and epigenome profiling and large-scale molecular profiling is key in redefining both the way pediatric hematologic cancers are categorized and how they are increasingly being treated, as molecular alterations are emerging as powerful prognostic markers and targets. With continued coordinated efforts to evaluate novel therapies in the pediatric population, genomically based therapies will become more common in the pediatric oncology clinic in the future. Rules for how treatment outcomes are analyzed are emerging, and molecular targets are being used to develop novel therapies. The landscape for pediatric blood cancer therapy is just beginning to realize the potential predicted by precision oncogenomics. These developments have created a new environment, one in which parents with a child newly diagnosed find themselves navigating a very different landscape than the one a parent might have encountered in 2010. In the end, the goal of oncogenomics research in children is translation to the clinic, so as to achieve accurate diagnosis, a clearer risk stratification, and effective, less toxic therapies. 

In this Topic, we invite authors from developed and developing countries to contribute original research and review articles focusing on different aspects of pediatric cancer development, causes, maintenance, and therapeutic strategies. We will consider articles on different pediatric cancers in relation to the developments in precision oncogenomics. This Topic is being run in collaboration with the Fondation Botnar.

Fondation Botnar is a philanthropic foundation based in Basel, Switzerland, that champions the use of AI and digital technologies to improve the health and wellbeing of children and young people in growing urban environments.

The contents of this Topic should provide an insight into current pediatric cancer precision medicine efforts in developed and developing countries, reflecting only a microcosm of the current applications of oncogenomics in this bustling space of clinical translation.

This Topic will publish research, commentaries, policy perspectives, historical insights, and clinical and laboratory observations.

The findings from the Topic will be presented in an international conference in the second half of 2021.

Prof. Dr. Gabriella Pravettoni
Prof. Dr. Jonathan A Lal
Dr. Denis Horgan
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Cancers cancers	5.2	7.4	2009	17.9 Days	CHF 2900
Journal of Personalized Medicine jpm	3.4	2.6	2011	17.8 Days	CHF 2600
International Journal of Environmental Research and Public Health ijerph	-	5.4	2004	29.6 Days	CHF 2500
Hemato hemato	-	-	2020	28.1 Days	CHF 1000
Adolescents adolescents	-	-	2021	37.2 Days	CHF 1000

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Published Papers (14 papers)

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All Cancers JPM IJERPH Hemato Adolescents

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Open AccessArticle

Incidence and Risk Factors for Cerebrovascular-Specific Mortality in Patients with Colorectal Cancer: A Registry-Based Cohort Study Involving 563,298 Patients

by Zhi-Hui Dai, Ming Tang, Yun-Liang Chen, Tao-Lan Zhang, Jing Li, Guo-Hua Lv, Yi-Guo Yan, Zhi-Hua Ouyang, Wei Huang and Ming-Xiang Zou

Cancers 2022, 14(9), 2053; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14092053 - 19 Apr 2022

Cited by 3 | Viewed by 2059

Abstract

Background: Colorectal cancer (CRC) is one of the most prevalent diseases and the second leading cause of death worldwide. However, the relationship between CRC and cerebrovascular-specific mortality (CVSM) remains elusive, and less is known about the influencing factors associated with CVSM in CRC. [...] Read more.

Background: Colorectal cancer (CRC) is one of the most prevalent diseases and the second leading cause of death worldwide. However, the relationship between CRC and cerebrovascular-specific mortality (CVSM) remains elusive, and less is known about the influencing factors associated with CVSM in CRC. Here, we aimed to analyze the incidence as well as the risk factors of CVSM in CRC. Methods: Patients with a primary CRC diagnosed between 1973 and 2015 were identified from the Surveillance Epidemiology and End Results database, with follow-up data available until 31 December 2016. Conditional standardized mortality ratios were calculated to compare the incidence of CVSM between CRC patients and the general U.S. population. Univariate and multivariate survival analyses with a competing risk model were used to interrogate the risk factors for CVSM. Results: A total of 563,298 CRC individuals were included. The CVSM in CRC patients was significantly higher than the general population in all age subgroups. Among the competing causes of death in patients, the cumulative mortality caused by cerebrovascular-specific diseases steadily increased during the study period. While age, surgery, other/unknown race and tumors located at the transverse colon positively influenced CVSM on both univariate and multivariate analyses, male patients and those who had radiotherapy, chemotherapy, a more recent year (2001–2015) of diagnosis, a grade II or III CRC, rectal cancer, or multiple primary or distant tumors experienced a lower risk of CVSM. Interpretation: Our data suggest a potential role for CRC in the incidence of CVSM and also identify several significant predictors of CVSM that may be helpful for risk stratification and the therapeutic optimization of cerebrovascular-specific diseases in CRC patients. Full article

(This article belongs to the Topic Oncogenomics and Pediatric Health)

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7 pages, 827 KiB  

Open AccessArticle

Correlation of Genetic Variants and the Incidence, Prevalence and Mortality Rates of Acute Lymphoblastic Leukemia

by Marianne Rodrigues Fernandes, Lui Wallacy Morikawa Souza Vinagre, Juliana Carla Gomes Rodrigues, Alayde Vieira Wanderley, Sweny Marinho Fernandes, Laura Patrícia Albarello Gellen, Angélica Leite de Alcântara, Beatriz Brilhante de Sousa, Rommel Mario Rodríguez Burbano, Paulo Pimentel de Assumpção, Sidney Emanuel Batista dos Santos and Ney Pereira Carneiro dos Santos

J. Pers. Med. 2022, 12(3), 370; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12030370 - 28 Feb 2022

Cited by 3 | Viewed by 2410

Abstract

Acute lymphoblastic leukemia (ALL) is the most common cancer during childhood, representing about 30–35% of cases. Its etiology is complex and not fully understood. ALL is influenced by genetic variants, and their frequencies (Fq) vary in different ethnic groups, which consequently could influence [...] Read more.

Acute lymphoblastic leukemia (ALL) is the most common cancer during childhood, representing about 30–35% of cases. Its etiology is complex and not fully understood. ALL is influenced by genetic variants, and their frequencies (Fq) vary in different ethnic groups, which consequently could influence the epidemiology of this cancer worldwide. The aim of this study was to investigate the correlation between the genetic variants and their impacts on incidence (IC), mortality (MT), and prevalence (PV) rates of ALL in different world populations. Methods: Sixty variants were selected from the literature with Genome Wide Association studies (GWAS). Information regarding allele Fq was selected from the 1000 Genomes platform. Epidemiological data were taken from the Global Burden of disease visualisations (GBD) Compare website. Statistical analyses were calculated in RStudio v.3.5.1 software. Results: Four variants demonstrated significant results in correlations with epidemiological data for ALL. The PAX5 gene variant (rs2297105) had an indirect relationship with PV and IC of ALL, showing that an increased Fq of this variant is related to low rates of both. An increased Fq of rs915172 in EPB4IL2 gene was also correlated with a lower IC of ALL. The rs1048943 of the CYP1A1 gene and the rs3088440 polymorphism of the CDKN2A gene were shown to have a direct proportional relationship with MT rate, showing that an increased Fq of these variants correlates with a worse prognosis worldwide. Conclusion: Our study points out four important variants for understanding the IC, PV, and MT rates for ALL. The ascertainment of these data may help to choose molecular markers to investigate the susceptibility and prognosis of ALL. Full article

(This article belongs to the Topic Oncogenomics and Pediatric Health)

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18 pages, 922 KiB  

Open AccessPerspective

Factors Affecting Citizen Trust and Public Engagement Relating to the Generation and Use of Real-World Evidence in Healthcare

by Denis Horgan, Bettina Borisch, Ivana Cattaneo, Mark Caulfield, Arturo Chiti, Christine Chomienne, Amanda Cole, Karen Facey, Allan Hackshaw, Minna Hendolin, Nadia Georges, Dipak Kalra, Birutė Tumienė and Martina von Meyenn

Int. J. Environ. Res. Public Health 2022, 19(3), 1674; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph19031674 - 01 Feb 2022

Cited by 5 | Viewed by 2987

Abstract

The potential for the use of real-world data (RWD) to generate real-world evidence (RWE) that can inform clinical decision-making and health policy is increasingly recognized, albeit with hesitancy in some circles. If used appropriately, the rapidly expanding wealth of health data could improve [...] Read more.

The potential for the use of real-world data (RWD) to generate real-world evidence (RWE) that can inform clinical decision-making and health policy is increasingly recognized, albeit with hesitancy in some circles. If used appropriately, the rapidly expanding wealth of health data could improve healthcare research, delivery of care, and patient outcomes. However, this depends on two key factors: (1) building structures that increase the confidence and willingness of European Union (EU) citizens to permit the collection and use of their data, and (2) development of EU health policy to support and shape data collection infrastructures, methodologies, transmission, and use. The great potential for use of RWE in healthcare improvement merits careful exploration of the drivers of, and challenges preventing, efficient RWD curation. Literature-based research was performed to identify relevant themes and discussion topics for two sets of expert panels, organized by the European Alliance for Personalised Medicine. These expert panels discussed steps that would enable a gradual but steady growth in the quantity, quality, and beneficial deployment of RWE. Participants were selected to provide insight based on their professional medical, economic, patient, industry, or governmental experience. Here, we propose a framework that addresses public trust and access to data, cross-border governance, alignment of evidence frameworks, and demonstrable improvements in healthcare decisions. We also discuss key case studies that support these recommendations, in accordance with the discussions at the expert panels. Full article

(This article belongs to the Topic Oncogenomics and Pediatric Health)

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12 pages, 570 KiB  

Open AccessArticle

Effectiveness of Surgical Approach of Insertion Ventilation Tubes (Tympanostomy) and Adenoidectomy in Comparison with Non-Surgical Approach (Watchful Waiting Approach) in Children at the Age between 1 and 6 and Who Suffer from Otitis Media with Effusion (OME) in 12-Month Period of Observation—The Retrospective Analysis

by Magdalena Beata Skarzynska, Elżbieta Gos, Natalia Czajka, Milaine Dominici Sanfis and Piotr Henryk Skarzynski

Int. J. Environ. Res. Public Health 2021, 18(23), 12502; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph182312502 - 27 Nov 2021

Cited by 4 | Viewed by 2128

Abstract

(1) Background: Otitis media with effusion (OME) is one of the most common diseases in childhood. The objective was to assess clinically the effectiveness of the surgical approach (tube insertion with adenoidectomy) in comparison with the non-surgical approach (watchful waiting) during a 12-month [...] Read more.

(1) Background: Otitis media with effusion (OME) is one of the most common diseases in childhood. The objective was to assess clinically the effectiveness of the surgical approach (tube insertion with adenoidectomy) in comparison with the non-surgical approach (watchful waiting) during a 12-month observation period. (2) Methods: This study was retrospective and obtained approval from the bioethics committee. The criteria of inclusion in the first group (surgical approach) were: (1) a diagnosis of chronic otitis media with effusion in children aged between 1 and 6 years; (2) their medical history showed that they had undergone adenoidectomy and tympanostomy with the insertion of ventilation tubes (VTs). The criteria for inclusion in the second group (non-surgery) were similar to the first group except that their medical history showed they had not undergone adenoidectomy or tympanostomy with the insertion of VTs. There were 422 children included in the surgical group and 50 children in the non-surgical group, and the period of observation was 12 months. (3) Results: For the entire surgical group, the number of healthy days ranged from 20 to 365, with a mean of 328.0 days (SD = 91.4).In the non-surgical group, the number of healthy days ranged from 13 to 365, with a mean of 169.2 days (SD = 127.3). The difference in the number of healthy days was statistically significant (p < 0.001). The certainty of treatment in the first group was higher than in the second group, and the number of days without recurrence was significantly higher than in the second group. In the first group, there were 71 recurrences from 422 children (16.8%), and, in the second subgroup, there were 40 recurrences of acute otitis media (AOM) from 50 children (80%). The RR was 0.21. (4) Conclusions: The surgical approach in children aged 1–6 years who have been diagnosed with otitis media with effusion is reasonable and beneficial for the child. Full article

(This article belongs to the Topic Oncogenomics and Pediatric Health)

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11 pages, 392 KiB  

Open AccessArticle

Down Syndrome in Brazil: Occurrence and Associated Factors

by Mariana Rabello Laignier, Luís Carlos Lopes-Júnior, Raquel Esperidon Santana, Franciéle Marabotti Costa Leite and Carolina Laura Brancato

Int. J. Environ. Res. Public Health 2021, 18(22), 11954; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph182211954 - 14 Nov 2021

Cited by 12 | Viewed by 2815

Abstract

Background: Down syndrome is the most frequent genetic cause of intellectual disability, with an estimated birth prevalence of 14 per 10,000 live births. In Brazil, statistical data on the occurrence of babies born with Down syndrome remain unclear. We aimed to estimate the [...] Read more.

Background: Down syndrome is the most frequent genetic cause of intellectual disability, with an estimated birth prevalence of 14 per 10,000 live births. In Brazil, statistical data on the occurrence of babies born with Down syndrome remain unclear. We aimed to estimate the occurrence of Down syndrome between 2012 and 2018, and to observe its association with maternal, gestational, paternal characteristics, and newborn vitality. Methods: A retrospective study was carried out using secondary data included in the Certificate of Live Birth in a state located in the southeastern region of Brazil. Data analysis was performed in the software Stata 14.1. Pearson’s chi-square test for bivariate analysis, and logistic regression for multivariate analysis were performed, with a 95% confidence interval (CI) and a significance of 5%. Results: We observed that 157 cases of Down syndrome were reported among 386,571 live births, representing an incidence of 4 in 10,000 live births. Down syndrome was associated with maternal age ≥ 35 years, paternal age ≥ 30 years, the performance of six or more prenatal consultations, prematurity, and low birth weight (p < 0.05). Conclusions: Women aged 35 and over were more likely to have children born with Down syndrome. In addition, there is an association of Down syndrome with premature birth, low birth weight, and the number of prenatal consultations (≥6). Full article

(This article belongs to the Topic Oncogenomics and Pediatric Health)

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Open AccessArticle

Effect of MHC Linked 7-Gene Signature on Delayed Hepatocellular Carcinoma Recurrence

by Fomaz Tariq, Walizeb Khan, Washaakh Ahmad, Syeda Kiran Riaz, Mahvish Khan, Subuhi Sherwani, Shafiul Haque, Muhammad Faraz Arshad Malik, Muhammad Jahangir Iftikhar, Saif Khan and Farhan Haq

J. Pers. Med. 2021, 11(11), 1129; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11111129 - 02 Nov 2021

Cited by 2 | Viewed by 2233

Abstract

Dysregulated immune response significantly affects hepatocellular carcinoma’s (HCC) prognosis. Human Leukocyte Antigens are key in devising immune responses against HCC. Here, we investigated how HLAs modulate HCC development at the transcriptomic level. RNA-seq data of 576 patients from two independent cohorts was retrieved. [...] Read more.

Dysregulated immune response significantly affects hepatocellular carcinoma’s (HCC) prognosis. Human Leukocyte Antigens are key in devising immune responses against HCC. Here, we investigated how HLAs modulate HCC development at the transcriptomic level. RNA-seq data of 576 patients from two independent cohorts was retrieved. The clinicopathological relevance of all HLA genes was investigated using Fisher-Exact, correlation, and Kaplan–Meier and cox regression survival tests. Clustering of ~800 immune-related genes against HLAs was completed using a ward-agglomerative method. Networks were generated using 40 HLA associated unique genes and hub genes were investigated. HLAs including HLA-DMA, HLA-DMB, HLA-DOA and HLA-DRB6 were associated with delayed recurrence in both discovery (204 HCC cases) and validation (372 HCC cases) cohorts. Clustering analyses revealed 40 genes associated with these four HLAs in both cohorts. A set of seven genes (NCF4, TYROBP, LCP2, ZAP70, PTPRC, FYN and WAS) was found co-expressed at gene–gene interaction level in both cohorts. Furthermore, survival analysis revealed seven HLA-linked genes as predictors of delayed recurrence. Multivariate analysis also predicted that mean expression of 7-gene is an independent predictor of delayed recurrence in both cohorts. We conclude that the expression of 7-gene signature may lead to improved patient prognosis. Further studies are required for consideration in clinical practice. Full article

(This article belongs to the Topic Oncogenomics and Pediatric Health)

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18 pages, 1040 KiB  

Open AccessFeature PaperArticle

Analysis of Polybrominated Diphenyl Ethers and Lipid Composition in Human Breast Milk and Their Correlation with Infant Neurodevelopment

by Ming-Hsien Tsai, How-Ran Chao, Wen-Li Hsu, Ching-Chung Tsai, Chu-Wen Lin and Chu-Huang Chen

Int. J. Environ. Res. Public Health 2021, 18(21), 11501; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph182111501 - 01 Nov 2021

Cited by 6 | Viewed by 3096

Abstract

Breastfeeding is recommended over formula feeding, but human breast milk (HBM) composition varies and can be affected by food additives. Whether flame-retardant polybrominated diphenyl ethers (PBDEs) found in HBM interact with lipid components of HBM to impede infant neurodevelopment is a critical public [...] Read more.

Breastfeeding is recommended over formula feeding, but human breast milk (HBM) composition varies and can be affected by food additives. Whether flame-retardant polybrominated diphenyl ethers (PBDEs) found in HBM interact with lipid components of HBM to impede infant neurodevelopment is a critical public health issue. Using lipidomic analysis, we examined the association of PBDEs in HBM and HBM lipid components with infant neurodevelopment. HBM samples (n = 100) were collected at the beginning stage of breastfeeding and analyzed for 30 PBDE congeners as well as a group of lipid components by using high-resolution gas chromatography, mass spectrometry, and liquid chromatography time-of-flight mass spectrometry. Infants were examined at 8 to 12 months of age by using the Bayley-III to assess neurodevelopment. A total of seven PBDEs, 35 lipids, and 27 fatty acids in HBM showed significant associations with Bayley-III scores. Multivariate analysis confirmed that these candidate PBDEs and lipid components were significant predictors of infant neurodevelopment. Eicosapentaenoic acid and docosapentaenoic acid in HBM showed no association with infant neurodevelopment in the general Taiwanese population. While certain PBDEs may play a role, our findings indicate that the lipid components of HBM are directly important for infant neurodevelopment. Full article

(This article belongs to the Topic Oncogenomics and Pediatric Health)

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15 pages, 679 KiB  

Open AccessArticle

Adolescents’ Alcohol Use: Does the Type of Leisure Activity Matter? A Cross-National Study

by Aranzazu Albertos, Ina Koning, Edgar Benítez and Jokin De Irala

Int. J. Environ. Res. Public Health 2021, 18(21), 11477; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph182111477 - 31 Oct 2021

Cited by 5 | Viewed by 2236

Abstract

The main objective of this study was to analyze the relationship between structured, unstructured, and family leisure activities on the frequency of adolescent alcohol intake across three different countries (Spain, Peru, and The Netherlands). The self-control of adolescents was also investigated as a [...] Read more.

The main objective of this study was to analyze the relationship between structured, unstructured, and family leisure activities on the frequency of adolescent alcohol intake across three different countries (Spain, Peru, and The Netherlands). The self-control of adolescents was also investigated as a moderator in the relationship between leisure activities and alcohol consumption. Methodology: This research involved 4608 adolescents aged between 12 and 17 from three countries (Spain, Peru, and The Netherlands). In Spain and Peru, data was collected through a self-report questionnaire which was part of the Your Life project. In The Netherlands, a self-questionnaire was used, collected by the University of Utrecht. A multiple logistic regression was performed for each country. Results: The results showed that participation in unstructured leisure activities increased the likelihood of drinking more frequently and more heavily in all three countries. Structured leisure activities, in general, did not have a significant predictive effect on alcohol consumption in any of the countries. Family leisure activities reduced the risk of engaging in yearly alcohol use and yearly binge drinking among adolescents, especially in The Netherlands and Spain. The protective effect of family leisure and unstructured leisure risk on yearly alcohol use applied especially to Dutch adolescents with a low level of self-control. Discussion: The article emphasizes the need for parents to engage in leisure activities with their child; participation in unstructured activities is not to be encouraged. Full article

(This article belongs to the Topic Oncogenomics and Pediatric Health)

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15 pages, 12309 KiB  

Open AccessArticle

Clinical Value of NGS Genomic Studies for Clinical Management of Pediatric and Young Adult Bone Sarcomas

by Miriam Gutiérrez-Jimeno, Piedad Alba-Pavón, Itziar Astigarraga, Teresa Imízcoz, Elena Panizo-Morgado, Susana García-Obregón, Ana Catalán-Lambán, Mikel San-Julián, José M. Lamo-Espinosa, Aizpea Echebarria-Barona, Marta Zalacain, Marta M. Alonso and Ana Patiño-García

Cancers 2021, 13(21), 5436; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13215436 - 29 Oct 2021

Cited by 4 | Viewed by 2094

Abstract

Genomic techniques enable diagnosis and management of children and young adults with sarcomas by identifying high-risk patients and those who may benefit from targeted therapy or participation in clinical trials. Objective: to analyze the performance of an NGS gene panel for the clinical [...] Read more.

Genomic techniques enable diagnosis and management of children and young adults with sarcomas by identifying high-risk patients and those who may benefit from targeted therapy or participation in clinical trials. Objective: to analyze the performance of an NGS gene panel for the clinical management of pediatric sarcoma patients. We studied 53 pediatric and young adult patients diagnosed with sarcoma, from two Spanish centers. Genomic data were obtained using the Oncomine Childhood Cancer Research Assay, and categorized according to their diagnostic, predictive, or prognostic value. In 44 (83%) of the 53 patients, at least one genetic alteration was identified. In 80% of these patients, the diagnosis was obtained (n = 11) or changed (n = 9), and thus genomic data affected therapy. The most frequent initial misdiagnosis was Ewing’s sarcoma, instead of myxoid liposarcoma (FUS-DDDIT3), rhabdoid soft tissue tumor (SMARCB1), or angiomatoid fibrous histiocytoma (EWSR1-CREB1). In our series, two patients had a genetic alteration with an FDA-approved targeted therapy, and 30% had at least one potentially actionable alteration. NGS-based genomic studies are useful and feasible in diagnosis and clinical management of pediatric sarcomas. Genomic characterization of these rare and heterogeneous tumors also helps in the search for prognostic biomarkers and therapeutic opportunities. Full article

(This article belongs to the Topic Oncogenomics and Pediatric Health)

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11 pages, 1866 KiB  

Open AccessArticle

Impact of Rehabilitation Intensity on 3-Year Mortality among Children with Moderate to Severe Cerebral Palsy: A Population-Based Cohort Study

by Chiao-Lin Hsu, Chia-Ling Hung, Shih-Ju Huang, Chun-Hao Yin, Chi-Hsiang Chu, Tsu-Jen Kuo and Yao-Min Hung

Int. J. Environ. Res. Public Health 2021, 18(18), 9932; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph18189932 - 21 Sep 2021

Cited by 1 | Viewed by 1941

Abstract

Though numerous studies demonstrated the positive effect of rehabilitation on cerebral palsy (CP) children, there was no literature addressing the role of rehabilitation on mortality among children with CP. Therefore, we aimed to evaluate the impact of rehabilitation intensity on mortality among children [...] Read more.

Though numerous studies demonstrated the positive effect of rehabilitation on cerebral palsy (CP) children, there was no literature addressing the role of rehabilitation on mortality among children with CP. Therefore, we aimed to evaluate the impact of rehabilitation intensity on mortality among children with moderate to severe CP. This retrospective cohort study was conducted by National Health Insurance Research Database in Taiwan. Children (<12 years) with newly diagnosed moderate to severe CP between 1 January 2000 and 31 December 2013 were included. All patients were followed up for 3 years after CP diagnosis or death or until 31 December 2013. The intensity of rehabilitation therapy within 6 months after CP diagnosis was categorized into <6 times and ≥6 times. The Cox proportional hazard analysis was used to determine the association between rehabilitation intensity and all-cause mortality after adjusting age, sex, other demographic factors and comorbidities. Among 3936 severe CP children, 164 (4.2%) died during the 3-year follow-up period. The mortality rate was higher among patients receiving rehabilitation < 6 times within 6 months than those ≥6 times within 6 months after adjusting demographic profile and comorbidities (adjust HR (aHR): 1.96, 95% CI 1.33–2.89, p < 0.001). We found that patients who were younger (aHR: 0.84, 95% CI 0.76–0.92, p < 0.001), who were receiving inpatient care more than twice in 1 year before their CP diagnosis (aHR: 2.88; 95% CI: 1.96–4.23; p < 0.001), and who have pneumonia (aHR: 1.41, 95% CI 1.00–1.96, p = 0.047), epilepsy (aHR: 1.41, 95% CI: 1.02–1.95, p = 0.039) and dysphagia (aHR: 1.55, 95% CI: 1.06–2.26, p = 0.024) have higher risk of mortality. Rehabilitation ≥ 6 times within 6 months has a potentially positive impact on pediatric CP survival. Besides having a younger age, being hospitalized more than twice within a year before diagnosis and having pneumonia, epilepsy and dysphagia were modifiable risk factors in clinical practice for these children. Full article

(This article belongs to the Topic Oncogenomics and Pediatric Health)

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15 pages, 1227 KiB  

Open AccessArticle

PD-L1 Expression Is Significantly Associated with Tumor Mutation Burden and Microsatellite Instability Score

by Yoon Ah Cho, Hyunwoo Lee, Deok Geun Kim, Hyunjin Kim, Sang Yun Ha, Yoon-La Choi, Kee-Taek Jang and Kyoung-Mee Kim

Cancers 2021, 13(18), 4659; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13184659 - 16 Sep 2021

Cited by 22 | Viewed by 3612

Abstract

Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC), microsatellite instability (MSI), and tumor mutation burden (TMB) have been proposed as a predictive biomarker to predict response to immune checkpoint blockade (ICB). We aimed to find the relationship of PD-L1 IHC to TMB and MSI using [...] Read more.

Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC), microsatellite instability (MSI), and tumor mutation burden (TMB) have been proposed as a predictive biomarker to predict response to immune checkpoint blockade (ICB). We aimed to find the relationship of PD-L1 IHC to TMB and MSI using a comprehensive cancer panel assay (CCPA) with >500 genes in advanced cancer patients. CCPA results from 588 archived tissue samples were analyzed for TMB and MSI. In seven samples, whole exome sequencing confirmed TMB with Pearson’s correlation coefficient of 0.972 and all MSI-high cases were validated by pentaplex PCR. Association of TMB and MSI with their corresponding PD-L1 IHC was analyzed. The median TMB value of 588 cases was 8.25 mutations (mut)/Mb (range 0–426.8) with different distributions among the tumor types, with high proportions of high-TMB (>10mut/Mb) in tumors from melanoma, colorectal, gastric, and biliary tract. The TMB values significantly correlated with PD-L1 expression, and this correlation was prominent in gastric and biliary tract cancers. Moreover, the MSI score, the proportion of unstable MSI sites to total assessed MSI sites, showed a significant correlation with the TMB values and PD-L1 scores. This study demonstrates that PD-L1 expression is significantly associated with TMB and MSI score and this correlation depends on the location of the primary tumor. Full article

(This article belongs to the Topic Oncogenomics and Pediatric Health)

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21 pages, 364 KiB  

Open AccessArticle

Effect of Genetic Variation in CYP450 on Gonadal Impairment in a European Cohort of Female Childhood Cancer Survivors, Based on a Candidate Gene Approach: Results from the PanCareLIFE Study

by M. E. Madeleine van der Perk, Linda Broer, Yutaka Yasui, Leslie L. Robison, Melissa M. Hudson, Joop S. E. Laven, Helena J. van der Pal, Wim J. E. Tissing, Birgitta Versluys, Dorine Bresters, Gertjan J. L. Kaspers, Andrica C. H. de Vries, Cornelis B. Lambalk, Annelies Overbeek, Jacqueline J. Loonen, Catharina C. M. Beerendonk, Julianne Byrne, Claire Berger, Eva Clemens, Uta Dirksen, Jeanette Falck Winther, Sophie D. Fosså, Desiree Grabow, Monica Muraca, Melanie Kaiser, Tomáš Kepák, Jarmila Kruseova, Dalit Modan-Moses, Claudia Spix, Oliver Zolk, Peter Kaatsch, Jesse H. Krijthe, Leontien C. M. Kremer, Russell J. Brooke, Jessica L. Baedke, Ron H. N. van Schaik, John N. van den Anker, André G. Uitterlinden, Annelies M. E. Bos, Flora E. van Leeuwen, Eline van Dulmen-den Broeder, Anne-Lotte L. F. van der Kooi, Marry M. van den Heuvel-Eibrink and on behalf of the PanCareLIFE Consortiumadd Show full author list remove Hide full author list

Cancers 2021, 13(18), 4598; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13184598 - 13 Sep 2021

Cited by 7 | Viewed by 2512

Abstract

Background: Female childhood cancer survivors (CCSs) carry a risk of therapy-related gonadal dysfunction. Alkylating agents (AA) are well-established risk factors, yet inter-individual variability in ovarian function is observed. Polymorphisms in CYP450 enzymes may explain this variability in AA-induced ovarian damage. We aimed to [...] Read more.

Background: Female childhood cancer survivors (CCSs) carry a risk of therapy-related gonadal dysfunction. Alkylating agents (AA) are well-established risk factors, yet inter-individual variability in ovarian function is observed. Polymorphisms in CYP450 enzymes may explain this variability in AA-induced ovarian damage. We aimed to evaluate associations between previously identified genetic polymorphisms in CYP450 enzymes and AA-related ovarian function among adult CCSs. Methods: Anti-Müllerian hormone (AMH) levels served as a proxy for ovarian function in a discovery cohort of adult female CCSs, from the pan-European PanCareLIFE cohort (n = 743; age (years): median 25.8, interquartile range (IQR) 22.1–30.6). Using two additive genetic models in linear and logistic regression, nine genetic variants in three CYP450 enzymes were analyzed in relation to cyclophosphamide equivalent dose (CED) score and their impact on AMH levels. The main model evaluated the effect of the variant on AMH and the interaction model evaluated the modifying effect of the variant on the impact of CED score on log-transformed AMH levels. Results were validated, and meta-analysis performed, using the USA-based St. Jude Lifetime Cohort (n = 391; age (years): median 31.3, IQR 26.6–37.4). Results: CYP3A4*3 was significantly associated with AMH levels in the discovery and replication cohort. Meta-analysis revealed a significant main deleterious effect (Beta (95% CI): −0.706 (−1.11–−0.298), p-value = 7 × 10⁻⁴) of CYP3A4*3 (rs4986910) on log-transformed AMH levels. CYP2B6*2 (rs8192709) showed a significant protective interaction effect (Beta (95% CI): 0.527 (0.126–0.928), p-value = 0.01) on log-transformed AMH levels in CCSs receiving more than 8000 mg/m² CED. Conclusions: Female CCSs CYP3A4*3 carriers had significantly lower AMH levels, and CYP2B6*2 may have a protective effect on AMH levels. Identification of risk-contributing variants may improve individualized counselling regarding the treatment-related risk of infertility and fertility preservation options. Full article

(This article belongs to the Topic Oncogenomics and Pediatric Health)

11 pages, 1056 KiB  

Open AccessArticle

The Epidemiology of Benign Proliferative Processes of the Skeletal System in Children

by Michal Rutkowski and Kinga Niewinska

Int. J. Environ. Res. Public Health 2021, 18(17), 9338; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph18179338 - 03 Sep 2021

Cited by 1 | Viewed by 1951

Abstract

A suspicion of a proliferative bone lesion in a child seems to be a major diagnostic problem for clinicians. There are no diagnostic and treatment algorithms described in the literature and no reliable cohort epidemiological data. Our study was conducted among 289 paediatric [...] Read more.

A suspicion of a proliferative bone lesion in a child seems to be a major diagnostic problem for clinicians. There are no diagnostic and treatment algorithms described in the literature and no reliable cohort epidemiological data. Our study was conducted among 289 paediatric patients (0–18 years old) with an initial diagnosis of a bone tumour or tumour-like lesion. The study comprised a retrospective epidemiological analysis, an assessment of the concordance of the initial diagnoses with the histopathological diagnoses and an analysis of the specific locations of the various bone lesions. The results obtained have made it possible to formulate the following conclusions. (1) The most common proliferative bone lesion in children is osteochondroma; also common are fibrous dysplasia, non-ossifying fibromas and bone cysts. (2) Verifying the initial diagnosis by means of biopsy is essential. (3) Osteochondromas are typically located in the metaphyses of long bones, fibrous dysplasia in the femur and skull, cyst-like lesions in the proximal humerus and non-osteochondral fibromas exclusively in the lower limbs. What could improve the quality of treatment for children with primary proliferative bone diseases is the establishment of centres of paediatric orthopaedic oncology skilled in early diagnosis and prompt management. Full article

(This article belongs to the Topic Oncogenomics and Pediatric Health)

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16 pages, 1359 KiB  

Open AccessReview

Effect of Distraction Intervention for Needle-Related Pain and Distress in Children: A Systematic Review and Meta-Analysis

by Mi-Kyoung Cho and Mi-Young Choi

Int. J. Environ. Res. Public Health 2021, 18(17), 9159; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph18179159 - 31 Aug 2021

Cited by 11 | Viewed by 6532

Abstract

A systematic review and meta-analysis conducted to evaluate the combined effect of distraction intervention for needle-related pain in order to provide the basis for developing an effective nursing intervention for children. We searched three electronic databases, PubMed, Embase, and CINAHL, for original articles [...] Read more.

A systematic review and meta-analysis conducted to evaluate the combined effect of distraction intervention for needle-related pain in order to provide the basis for developing an effective nursing intervention for children. We searched three electronic databases, PubMed, Embase, and CINAHL, for original articles published in the period from 1 January 2011 to 31 July 2019. In addition, a manual search was performed on the basis of references in the literature and the references of the articles in pursuit of comprehensive data until 10 December 2019. Meta-analysis was performed by the synthesis of the effect size, homogeneity, heterogeneity, and trim-and-fill method using MIX 2.0 Pro. Well-planned RCTs, single-center studies, high-quality studies, participants older than 10 years of age, and visual and clown distraction interventions were effective for needle-related pain and distress management among children. The results showed evidence supporting the effect of distraction interventions for children’s needle-related pain and distress. Through this review, strategies were identified to design better interventions to improve the outcomes. Full article

(This article belongs to the Topic Oncogenomics and Pediatric Health)

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