scholarly journals O2A.3 Increased risk of central nervous system tumors with carbamate insecticide use in the prospective cohort agrican

2019 ◽  
Vol 76 (Suppl 1) ◽  
pp. A13.2-A14
Author(s):  
Clément Piel ◽  
Camille Pouchieu ◽  
Lucile Migault ◽  
Beatrix Béziat ◽  
Mathilde Boulanger ◽  
...  

BackgroundPesticide exposures are suspected to be implicated in the excess of Central Nervous System (CNS) tumors observed in farmers, but evidence concerning individual pesticides remains limited. Carbamate insecticides, used on a wide range of crops, have shown evidence of carcinogenicity in some experimental studies. In the cohort AGRICAN (AGRIculture and CANcer), we assessed the associations between potential exposures to carbamate insecticides and the incidence of CNS tumors, overall and by histological subtype.MethodsAGRICAN enrolled 181 842 participants involved in agriculture. Incident CNS tumors were identified by linkage with cancer registries from enrolment (2005–2007) until 2013. Carbamate exposure was assessed by combining information on lifetime periods of pesticide use on crop or livestock and the French crop-exposure matrix PESTIMAT, individually for each of the 19 carbamate insecticides registered in France since 1950. Associations were estimated using proportional hazards models with age as the underlying timescale, adjusting for gender, educational level and smoking.ResultsDuring a 6.9 year average follow-up, 381 incident cases of CNS tumors occurred, including 164 gliomas and 134 meningiomas. Analyses showed increased risks of CNS tumors with overall exposure to carbamate insecticides and linear trends with duration of use of each carbamate. Considering tumor subtypes, hazard ratios for gliomas ranged from 1.18 for thiofanox to 4.60 for formetanate and for meningiomas from 1.51 for carbaryl to 3.67 for thiofanox.ConclusionsFindings reinforce carcinogenicity evidence for already suspected active ingredients and draw attention to additional active ingredients, notably used on fruit trees, vineyards, potatoes and beets.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maral Adel Fahmideh ◽  
Erin C. Peckham-Gregory ◽  
Jeremy M. Schraw ◽  
Murali Chintagumpala ◽  
Stephen C. Mack ◽  
...  

AbstractCentral nervous system (CNS) tumors are the most common solid tumors in children. Findings on the role of maternal and perinatal factors on the susceptibility or outcome of these tumors are inconclusive. Therefore, we investigated the association between these early-life factors, risk, and survival of pediatric CNS tumors, using data from one of the world’s largest and most diverse cancer registries. Information on pediatric CNS tumor cases (n = 1950) for the period 1995–2011 was obtained from the Texas Cancer Registry. Birth certificate controls were frequency-matched on birth year at a ratio of 10:1 for the same period. Evaluated maternal and perinatal variables were obtained from birth records. Unconditional logistic regression was used to generate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for etiological factors. Additionally, Cox proportional hazards regression was employed to assess adjusted hazard ratios (HRs) and 95% CIs for survival factors. The results indicated that Hispanic and non-Hispanic black mothers were less likely to have children with CNS tumors compared to non-Hispanic white mothers (OR 0.88 [95% CI 0.78–0.98] P-value = 0.019; OR 0.79 [95% CI 0.67–0.93 P-value = 0.004], respectively). Infants born large for gestational age (OR 1.26 [95% CI 1.07–1.47] P-value = 0.004) and those delivered pre-term (OR 1.19 [95% CI 1.04–1.38] P-value = 0.013) showed an increased risk of CNS tumors. Infants born by vaginal forceps or vacuum delivery had a higher risk of CNS tumors compared to those born by spontaneous vaginal delivery (OR 1.35 [95% CI 1.12–1.62] P-value = 0.002). Additionally, offspring of Hispanic and non-Hispanic black mothers showed a higher risk of death (HR 1.45 [95% CI 1.16–1.80] P-value = 0.001; HR 1.53 [95% CI 1.12–2.09] P-value = 0.008, respectively). Infants born by cesarean had a higher risk of death compared to those delivered vaginally (HR 1.28 [95% CI 1.05–1.57] P-value = 0.016). These findings indicate the important role of maternal and perinatal characteristics in the etiology and survival of these clinically significant malignancies.


2020 ◽  
Vol 15 (2) ◽  
pp. 131-136
Author(s):  
Jeronimo Espinosa ◽  
Paulino A. Alvarez ◽  
Veronica Castro ◽  
Maria F. Caceres ◽  
Maria C. Soler-Riera ◽  
...  

Background: Central Nervous System (CNS) depressants like antipsychotics, opioids, benzodiazepines and zolpidem are frequently used by patients of a wide range of ages. Uncertainty remains about their effect in very old adults (>80 years old) and their potential for pharmacodynamic and pharmacokinetic drug-drug interactions in this population. Objective: To assess if the use of CNS depressants is associated with a higher risk of hospitalization due to community-acquired pneumonia (CAP) in very old patients. Methods: In this prospective study, 362 patients over 80 years of age who had been consequently admitted to the general ward of a teaching hospital were examined. Each patient was assessed, by our pharmacovigilance team within 24 hours of admission, to identify outpatient medication use and potential drug-drug interactions. Results: The overall use of CNS depressants as a group was not associated with a higher risk of admission due to CAP in very old patients (55% vs. 49%; OR=1.28 [0.76-2.16], p=0.34). However, the use of antipsychotics was associated with a higher rate of admissions due to CAP in this population (OR=1.98 [1.10-3.57], p=0.02). No association was seen between opioids (p=0.27), zolpidem (p=0.83), or benzodiazepines (p=0.15) and the rate of admissions due to CAP in these patients. Moreover, pharmacodynamic or pharmacokinetic interactions leading to CNS depression were equally found in patients admitted for CAP and those admitted for other reasons. Conclusion: The use of antipsychotics in very old adults was associated with an increased risk of hospital admission due to CAP. This suggests that the use of these medications in this population should be done with caution. No association was observed with opioids, benzodiazepines and zolpidem with the latter outcome.


2018 ◽  
Vol 6 (10) ◽  
pp. 100-109
Author(s):  
Meena B. Patil ◽  
Manjiri N. Karandikar

Background: Tumors of Central Nervous System constitute approximately 2% of all malignancies. Cancers of the central nervous system (CNS) are considered to be among the most notorious of all cancers. Low-grade cns tumors have been found over time to progress to high grade tumors. CNS is a common site for metastasis from other organs. Due to newer techniques used in radio diagnosis and stereotactic biopsies, more & more CNS tumors are being diagnosed & are being operated upon. Aims and objectives: The objective of this article is to provide an overview of intracranial and intraspinal space occupying lesions at a single tertiary care referral center. The aim was to study incidence of various lesions in light of the   WHO classification of tumours of the central nervous system, 2016 and to study relevant statistics. Material and methods: A total of 124 cases were received between January,2007 & December, 2011 at Bharati Vidyapeeth Deemed University Medical College and Hospital, Pune. Intraoperative diagnosis was desired in 70 cases. The final diagnoses in all the cases were made on Hematoxylin and Eosin stained slides of routinely processed tissue. Results: Neoplastic lesions comprised 83.88 %, including metastatic tumors while 16.12 % were nonneoplastic.  A wide range of histopathological spectrum of CNS tumors was observed and was classified according to WHO classification of CNS tumors, 2016. The primary CNS tumors were graded from Grade I to IV according to WHO grading system, 2016. Astrocytic tumors constituted the largest category with 33 cases and most of the astrocytomas were grade II at the time of diagnosis. Incidence was more in females than males and maximum number of lesions were seen in fifth and sixth decades of life. Conclusion: This study highlights the histological diversity of CNS tumors in both adults and children. The most common destructive but nonneoplastic lesions like, infections/abscesses, infarct and cysts can be diagnosed, by crush cytology and frozen section for the definitive management.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii320-iii320
Author(s):  
Daniel Moreira ◽  
Ibrahim Qaddoumi ◽  
Nickhill Bhakta ◽  
Amar Gajjar ◽  
Carlos Rodriguez-Galindo

Abstract Although approximately 90% of pediatric cancer cases exist in low- and middle-income countries, the magnitude of the global burden of pediatric central nervous system (CNS) tumors remains poorly quantified. METHODS: Data from International Incidence of Childhood Cancer-3 and CONCORD-3, which include observed incidence and survival from population-based cancer registries (PBCR), and from GLOBOCAN 2018 and Global Burden of Disease 2016, which produce burden estimates from observed and modelled data, were used to analyze epidemiologic characteristics and correlations for CNS tumors globally. Data from The World Bank were used for national macroeconomic variables. RESULTS: The majority of countries are not covered by PBCR, with information on incidence and survival available for 37% and 27% of countries, respectively. Survival data is not available for any low-income country. The incidence of CNS tumors varies markedly, from 0.4 to 49 x106 person-years, the greatest variability in pediatric cancer subgroups. Modelled data suggests that approximately 40,000 incident cases and 19,000 deaths occur from CNS tumors worldwide. When country-level data are segregated based on World Bank groups, a difference in incidence and survival exists (p<0.05). A higher national health expenditure correlates with both an increased incidence and survival of CNS tumors, while the inverse is true for under-5 mortality (p<0.05). CONCLUSIONS: Scarce facts are available, but this analysis establishes a link between national income and epidemiologic parameters for CNS tumors. In this context, carefully designed initiatives, focusing on a health-systems approach are critical to meet the global challenge of pediatric CNS tumors.


2019 ◽  
Vol 72 (8) ◽  
pp. 1437-1441
Author(s):  
Pavel Dyachenko ◽  
Igor Filchakov ◽  
Anatoly Dyachenko ◽  
Victoria Kurhanskaya

Introduction: Viral encephalitis accounts for 40-70% of all cases worldwide, central nervous system infections pose a diagnostic challenge because clinical manifestations are not typically pathognomonic for specific pathogens, and a wide range of agents can be causative. The aim: To assess the diagnostic value of intrathecal synthesis of specific antibodies in patients with inflammatory lesions of the central nervous system. Materials and methods: Within the framework of the study, two groups of 90 people in each were formed from the patients with neuroinfections admitted to our Center. Intrathecal synthesis (ITS) of total (unspecific) IgG in members of one of group (group of compare) was determined. Brain synthesis of specific antibodies (Ab) to some neurotropic pathogens (herpes simplex virus 1/2, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, rubella virus, Borrelies) was studied in the second group of patients (group of interest). There were no statistically significant differences between groups by gender and age. Encephalitis and encephalomyelitis prevailed among patients of both groups Results: ITS of total IgG was established in 30 (33.3 ± 6.1 %) patients of the first group with IgG index more than 0.6 indicating on inflammatory process in CNS and no marked changes of CSF. ITS of specific Ab was determined in 23 of 90 (25.6 ± 4.6 %) patients included into group of interest. In more than half of cases Ab to several infectious agents were detected simultaneously. ITS of various specificity, in particular, to measles and rubella viruses, and VZV, known as MRZ-reaction, is characteristic of some autoimmune lesions of CNS, multiple sclerosis first of all. In fact, further research of 5 patients with MRZ-reaction confirmed their autoimmune failure of CNS. Detection of ITS in the CSF samples didn’t depend on concentration of specific Ab in serum and CSF and wasn’t followed by HEB dysfunctions which were observed with the same frequency in patients with or without ITS (13.0 % and 13.6 % respectively). Conclusion: Specific Ab synthesis to several neurotropic pathogens in the CSF of significant part of examined patients was established. Thus, diagnostic value of ITS of specific immunoglobulins seems to be limited to cases in which autoimmune damage of the CNS is suspected.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii438-iii438
Author(s):  
Kathleen Dorris ◽  
Jessica Channell ◽  
Ashley Mettetal ◽  
Molly Hemenway ◽  
Natalie Briones ◽  
...  

Abstract BACKGROUND Cannabinoids, including cannabidiol (CBD) and tetrahydrocannabinol (THC), are a class of compounds found in marijuana. Numerous studies in adults have examined cannabinoid use in management of cancer-related symptoms such as nausea, anorexia, and pain. Less is known about the use in the pediatric oncology population. METHODS A prospective observational study has been ongoing since 2016 at Children’s Hospital Colorado to evaluate cannabinoids’ impact using PedsQL™ modules on quality of life of pediatric patients with central nervous system (CNS) tumors who are 2–18 years old. Laboratory assessments of T-cell activity and pharmacokinetics of CBD, THC and associated metabolites are in process. Diaries with exploratory information on cannabinoid use patterns are being collected. RESULTS Thirty-three patients (14:19; male:female) have been enrolled with a median age of 6.4 years (range, 2.9–17.7 years). The most common tumor type in enrolled patients is embryonal tumors (13/33; 39%). Nine (27%) patients have low-grade glial/glioneuronal tumors, and eight (24%) had high-grade/diffuse midline gliomas. The remaining patients had ependymoma or craniopharyngioma. The median time on cannabinoids is 9 months. Most (n=20) patients have used oral products with CBD and THC. One patient continues on cannabinoid therapy in follow up. Preliminary immune function analyses identified impaired neutrophil superoxide anion production and chemotaxis in patients taking cannabinoids at early time points on therapy. CONCLUSIONS Families of children with various CNS tumors are pursuing cannabinoid therapy for both antitumor and supportive care purposes. Analysis of the impact of cannabinoids on patients’ quality of life is ongoing.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii430-iii430
Author(s):  
Ross Mangum ◽  
Jacquelyn Reuther ◽  
Koel Sen Baksi ◽  
Ryan C Zabriskie ◽  
Ilavarasi Gandhi ◽  
...  

Abstract BACKGROUND The role of plasma cell-free DNA (cfDNA) as a cancer biomarker for tracking treatment response and detecting early relapse has been well described for solid tumors outside the central nervous system (CNS). However, the presence of a blood-brain barrier complicates the application of plasma cfDNA analysis for patients with CNS malignancies. METHODS cfDNA was extracted from plasma of pediatric patients with CNS tumors utilizing a QIAmp® MinElute® kit and quantitated with Qubit 2.0 Fluorometer. Extensive genomic testing, including targeted DNA and RNA solid tumor panels, exome and transcriptome sequencing, as well as copy number array, was performed on matched tumor samples as part of the Texas KidsCanSeq study. An Archer® Reveal ctDNA28 NGS kit was then used for assaying the sensitivity of detecting tumor-specific mutations in the plasma of these patients. RESULTS A median of 10.7ng cfDNA/mL plasma (Interquartile range: 6.4 – 15.3) was extracted from 78 patients at time of study enrollment. Longitudinal samples from 24 patients exhibited a median yield of 7.7ng cfDNA/mL plasma (IQR: 5.9 – 9.1). An initial cohort of 6 patients was identified with 7 somatic variants covered by the Archer® Reveal kit. Four of seven mutations identified in matched tumor specimens were detected in patient plasma at variant allele frequencies ranging from 0.2–1%. CONCLUSIONS While challenging, detection of cfDNA in the plasma of pediatric patients with CNS tumors is possible and is being explored in a larger patient cohort along with pilot studies investigating cerebrospinal fluid as an additional source for tumor-specific cfDNA.


2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Berendt Agnieszka ◽  
Wójtowicz-Marzec Monika ◽  
Wysokińska Barbara ◽  
Kwaśniewska Anna

Abstract Background Haemophilia A is an X-linked genetic condition which manifests itself mainly in male children in the first 2 years of life, during gross motor skill development. This disorder is rare in females. The clinical manifestation of severe haemophilia in preterm infants poses a great challenge to the therapeutic team. As extreme prematurity is linked to an increased risk of central nervous system or gastrointestinal bleeding, a well-informed and balanced treatment from the first days of life is crucial to prevent long-term damage. Haemophilia is most commonly caused by inheriting defective genes, and can also be linked to skewed X inactivation and Turner syndrome. The coincidental occurrence of haemophilia A and Turner syndrome is extremely rare, with only isolated cases described to date. Hence, a multidisciplinary approach is needed. Case presentation The authors report on a preterm girl (gestational age 28 weeks) diagnosed with haemophilia and Turner syndrome. The first manifestation of haemophilia was prolonged bleeding from injection sites on the second day of life. Indeterminate aPTT and factor VIII level < 1% confirmed the diagnosis of haemophilia A. Dysmorphic features which did not match the typical clinical picture of haemophilia, the female sex, and a negative paternal family history led to the diagnosis of Turner syndrome. While in hospital, the girl received multiple doses of recombinant factor VIII in response to prolonged bleedings from the injection sites and from a nodule on the girl’s head, and before and after retinal laser photocoagulation. No central nervous system or abdominal cavity bleeding was observed. The substitutive therapy was complicated by the development of factor VIII inhibitor (anti-factor VIII (FVIII) antibodies). Treatment was continued with recombinant factor VIIa. This article aims at demonstrating the complexity of the diagnostics and treatment of a preterm child with two genetic disorders. Conclusions Haemophilia should always be considered in the differential diagnosis of prolonged bleeding, even in patients with a negative family history. In the case of coinciding atypical phenotypic features, further diagnostics for another genetic disease are recommended. Infant care should follow current care standards, while considering certain individual features.


Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3028
Author(s):  
George I. Lambrou ◽  
Apostolos Zaravinos ◽  
Maria Braoudaki

Despite extensive experimentation on pediatric tumors of the central nervous system (CNS), related to both prognosis, diagnosis and treatment, the understanding of pathogenesis and etiology of the disease remains scarce. MicroRNAs are known to be involved in CNS tumor oncogenesis. We hypothesized that CNS tumors possess commonly deregulated miRNAs across different CNS tumor types. Aim: The current study aims to reveal the co-deregulated miRNAs across different types of pediatric CNS tumors. Materials: A total of 439 CNS tumor samples were collected from both in-house microarray experiments as well as data available in public databases. Diagnoses included medulloblastoma, astrocytoma, ependydoma, cortical dysplasia, glioblastoma, ATRT, germinoma, teratoma, yoc sac tumors, ocular tumors and retinoblastoma. Results: We found miRNAs that were globally up- or down-regulated in the majority of the CNS tumor samples. MiR-376B and miR-372 were co-upregulated, whereas miR-149, miR-214, miR-574, miR-595 and miR-765 among others, were co-downregulated across all CNS tumors. Receiver-operator curve analysis showed that miR-149, miR-214, miR-574, miR-595 and miR765 could distinguish between CNS tumors and normal brain tissue. Conclusions: Our approach could prove significant in the search for global miRNA targets for tumor diagnosis and therapy. To the best of our knowledge, there are no previous reports concerning the present approach.


2021 ◽  
Author(s):  
A McCauley Massie ◽  
Jonathan Ebelhar ◽  
Kristen E Allen ◽  
Nicholas P DeGroote ◽  
Karen Wasilewski-Masker ◽  
...  

Abstract Background Children with brain and central nervous system (CNS) tumors experience substantial challenges to their quality of life during their disease course. These challenges are opportunities for increased subspecialty palliative care (PC) involvement. Palliative opportunities have been defined in the pediatric oncology population, but the frequency, timing, and factors associated with palliative opportunities in pediatric patients with CNS tumors are unknown. Methods A single-institution retrospective review was performed on children ages 0-18 diagnosed with a CNS tumor who died between 01/01/2012-11/30/2017. Nine palliative opportunities were defined prior to data collection (progression; relapse; admission for severe symptoms; intensive care admission; bone marrow transplant; phase 1 trial; hospice; do-not-resuscitate (DNR) order). Demographic, disease, treatment, palliative opportunity, and end-of-life data were collected. Opportunities were evaluated over quartiles from diagnosis to death. Results Amongst 101 patients with a median age at death of eight years (Interquartile range, IQR=8.0, range 0-22), there was a median of seven (IQR=6) palliative opportunities per patient, which increased closer to death. PC consultation occurred in 34 (33.7%) patients, at a median of 2.2 months before death, and was associated with having a DNR order (p=0.0028). Hospice was involved for 72 (71.3%) patients. Conclusion Children with CNS tumors suffered repeated events warranting PC yet received PC support only one-third of the time. Mapping palliative opportunities over the cancer course promotes earlier timing of PC consultation which can decrease suffering and resuscitation attempts at the end-of-life.


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