Applications for fluoropolymers and PFOA include surface coatings for stain, oil, and water resistance on household products, carpets, textiles, and food packaging; personal care products; seals; ...coatings for cables and wires; and construction materials. Since the previous classification of PFOA (as “possibly carcinogenic to humans”, Group 2B) by the IARC Monographs in 2014,2 many new studies have investigated the association between exposure to PFOA and cancer in experimental animals and humans, as well as mechanistic endpoints relevant to the key characteristics of carcinogens. ...PFOA induces oxidative stress, modulates receptor-mediated effects (via PPARα, CAR/PXR, and PPARγ), and alters cell proliferation, cell death, and nutrient and energy supply in human primary cells and experimental systems. For testicular cancer, additional evidence was a positive association in an ecological analysis conducted by the Working Group of available data on orchiectomies from the Veneto region of Italy, and a US study finding no associations.9 For all other cancers, the evidence was “inadequate”, as there were only sporadic positive findings.
•Reviewed evidence indicates potential effects of low doses of IR on cognition.•Gaps in our understanding of radiation induced cognitive deficit were identified.•Childhood cancer, A-bomb survivors ...and occupational cohorts may be informative to study radiation cognitive changes.•Animal models may elucidate the mechanism of radiation induced cognitive effects.
The last decades have seen increased concern about the possible effects of low to moderate doses of ionizing radiation (IR) exposure on cognitive function.
An interdisciplinary group of experts (biologists, epidemiologists, dosimetrists and clinicians) in this field gathered together in the framework of the European MELODI workshop on non-cancer effects of IR to summarise the state of knowledge on the topic and elaborate research recommendations for future studies in this area.
Overall, there is evidence of cognitive effects from low IR doses both from biology and epidemiology, though a better characterization of effects and understanding of mechanisms is needed.
There is a need to better describe the specific cognitive function or diseases that may be affected by radiation exposure. Such cognitive deficit characterization should consider the human life span, as effects might differ with age at exposure and at outcome assessment.
Measurements of biomarkers, including imaging, will likely help our understanding on the mechanism of cognitive-related radiation induced deficit. The identification of loci of individual genetic susceptibility and the study of gene expression may help identify individuals at higher risk.
The mechanisms behind the radiation induced cognitive effects are not clear and are likely to involve several biological pathways and different cell types.
Well conducted research in large epidemiological cohorts and experimental studies in appropriate animal models are needed to improve the understanding of radiation-induced cognitive effects. Results may then be translated into recommendations for clinical radiation oncology and imaging decision making processes.
•We reviewed the evidence on possible neurodevelopmental effects of low-to-moderate doses of ionizing radiation.•Selected studies were heterogeneous in terms of outcome and exposure assessment.•The ...strength of evidence for an effect on general cognition and language was limited.•The evidence for an effect on other neurodevelopment domains was inadequate.•There was too little evidence to evaluate a possible difference in risk for exposure in utero compared to in childhood.
The neurodevelopmental effects of high doses of ionizing radiation (IR) in children are well established. To what extent such effects exist at low-to-moderate doses is unclear. Considering the increasing exposure of the general population to low-to-moderate levels of IR, predominantly from diagnostic procedures, the study of these effects has become a priority for radiation protection.
We conducted a systematic review of the current evidence for possible effects of low-to-moderate IR doses received during gestation, childhood and adolescence on different domains of neurodevelopment.
Searches were performed in PubMed, Scopus, EMBASE and Psychinfo on the 6th of June 2017 and repeated in December 2018.
We included studies evaluating the association between low-to-moderate IR doses received during gestation, childhood and adolescence, and neurodevelopmental functions.
Studies were evaluated using the Cochrane Collaboration′s risk of bias tool adapted to environmental sciences. A qualitative synthesis was performed.
A total of 26 manuscripts were finally selected. Populations analyzed in these publications were exposed to the following sources of IR: atomic bomb (Hiroshima and Nagasaki), diagnostic/therapeutic radiation, and Chernobyl and nuclear weapon testing fallout.
There was limited evidence for an association between low-to-moderate doses of IR and a decrease in general cognition and language abilities, that is, a causal interpretation is credible, but chance or confounding cannot not be ruled out with reasonable confidence. Evidence for a possible stronger effect when exposure occurred early in life, in particular, during the fetal period, was inadequate. Evidence for an association between IR and other specific domains, including attention, executive function, memory, processing speed, visual-spatial abilities, motor and socio-emotional development, was inadequate, due to the very limited number of studies found.
Overall, depending on the domain, there was limited to inadequate evidence for an effect of low-to-moderate IR doses on neurodevelopment. Heterogeneity across studies in terms of outcome and exposure assessment hampered any quantitative synthesis and any stronger conclusion. Future research with adequate dosimetry and covering a range of specific neurodevelopmental outcomes would likely contribute to improve the body of evidence.
The systematic review protocol was registered in PROSPERO (registration number CRD42018091902).
Medical diagnostic X-rays are an important source of ionizing radiation (IR) exposure in the general population; however, it is unclear if the resulting low patient doses increase lymphoma risk. We ...examined the association between lifetime medical diagnostic X-ray dose and lymphoma risk, taking into account potential confounding factors, including medical history. The international Epilymph study (conducted in the Czech-Republic, France, Germany, Ireland, Italy, and Spain) collected self-reported information on common diagnostic X-ray procedures from 2,362 lymphoma cases and 2,465 frequency-matched (age, sex, country) controls. Individual lifetime cumulative bone marrow (BM) dose was estimated using time period-based dose estimates for different procedures and body parts. The association between categories of BM dose and lymphoma risk was examined using unconditional logistic regression models adjusting for matching factors, socioeconomic variables, and the presence of underlying medical conditions (atopic, autoimmune, infectious diseases, osteoarthritis, having had a sick childhood, and family history of lymphoma) as potential confounders of the association. Cumulative BM dose was low (median 2.25 mGy) and was not positively associated with lymphoma risk. Odds ratios (ORs) were consistently less than 1.0 in all dose categories compared to the reference category (less than 1 mGy). Results were similar after adjustment for potential confounding factors, when using different exposure scenarios, and in analyses by lymphoma subtype and by type of control (hospital-, population-based). Overall no increased risk of lymphoma was observed. The reduced ORs may be related to unmeasured confounding or other sources of systematic bias.We found little evidence that chronic medical conditions confound lymphoma risk and medical radiation associations.
20 years ago, 3 manuscripts describing doses and potential cancer risks from CT scans in children raised awareness of a growing public health problem. We reviewed the epidemiological studies that ...were initiated in response to these concerns that assessed cancer risks from CT scans using medical record linkage. We evaluated the study methodology and findings and provide recommendations for optimal study design for new efforts. We identified 17 eligible studies; 13 with published risk estimates, and 4 in progress. There was wide variability in the study methodology, however, which made comparison of findings challenging. Key differences included whether the study focused on childhood or adulthood exposure, radiosensitive outcomes (
leukemia, brain tumors) or all cancers, the exposure metrics (
organ doses, effective dose or number of CTs) and control for biases (
latency and exclusion periods and confounding by indication). We were able to compare results for the subset of studies that evaluated leukemia or brain tumors. There were eight studies of leukemia risk in relation to red bone marrow (RBM) dose, effective dose or number of CTs; seven reported a positive dose-response, which was statistically significant (
< 0.05) in four studies. Six of the seven studies of brain tumors also found a positive dose-response and in five, this was statistically significant. Mean RBM dose ranged from 6 to 12 mGy and mean brain dose from 18 to 43 mGy. In a meta-analysis of the studies of childhood exposure the summary ERR/100 mGy was 1.78 (95%CI: 0.01-3.53) for leukemia/myelodisplastic syndrome (
= 5 studies) and 0.80 (95%CI: 0.48-1.12) for brain tumors (
= 4 studies) (p-heterogeneity >0.4). Confounding by cancer pre-disposing conditions was unlikely in these five studies of leukemia. The summary risk estimate for brain tumors could be over estimated, however, due to reverse causation. In conclusion, there is growing evidence from epidemiological data that CT scans can cause cancer. The absolute risks to individual patients are, however, likely to be small. Ongoing large multicenter cohorts and future pooling efforts will provide more precise risk quantification.
On December 3, 2019, I (E. P.) was defending my doctoral thesis in Barcelona, Spain, and everything was set up to continue with my research career in public health: I was supposed to start a ...postdoctoral position in the United States by May 2020. However, because of the pandemic, as well as travel and visa restrictions, I was not able to start it, so I was back in Italy living with my parents. I was fortunate, because after months of uncertainty, during which I was supported by my family and a shortterm scholarship, I started my planned US postdoc in September 2020, working remotely. I also realized that my struggle was not exceptional. My PhD desk-mate (I. A.-P.) in the United States was dealing with the approaching end of her postdoctoral fellowship, which she managed to extend for several months. We shared our own concerns and struggles, and we reflected on the challenges that we, and our peers, were facing. Indeed, our ongoing personal experience of such a tortuous and uncertain career transition during the pandemic is common to many early-career researchers,1 including those in public health-related disciplines.2 Many early-career researchers and trainees are currently struggling, as emerged from a recent Nature survey, in which 61% of respondents reported that their career prospects had been "negatively impacted" by the pandemic and another 25% said they "possibly" had been.3This pandemic has shown how crucial strong public health research infrastructures are. Researchers have an important role in being consulted by governments, interviewed by the media, and contributing to the advancement of knowledge and to the scientific debate. Paradoxically, however, the current crisis may have negatively affected scientists' career perspectives. The pandemic may have worsened an already existing job precarity, as the availability of PhD and postdoc positions has become more limited through a reduction in university funding or mobility and visa restrictions.4 The difficulty in advancing research projects-for example, due to delays in data collection-might particularly affect those scientists with shortterm contracts whose career advancement depends on delivering results quickly.3 Additionally, career advancement might be challenged by the lack of traditional networking opportunities, such as in-person conferences or shortterm internships. Finally, uncertainty, precariousness, and family or community obligations may affect the motivation and productivity of early-career researchers.
Since the 1980s, both the incidence of differentiated thyroid cancer (DTC) and use of radioactive iodine (RAI) treatment increased markedly. RAI has been associated with an increased risk of ...leukemia, but risks of second solid malignancies remain unclear. We aimed to quantify risks of second malignancies associated with RAI treatment for DTC in children and young adults, who are more susceptible than older adults to the late effects of radiation.
Using nine US SEER cancer registries (1975-2017), we estimated relative risks (RRs) for solid and hematologic malignancies associated with RAI (yes
no or unknown) using Poisson regression among ≥ 5- and ≥ 2-year survivors of nonmetastatic DTC diagnosed before age 45 years, respectively.
Among 27,050 ≥ 5-year survivors (median follow-up = 15 years), RAI treatment (45%) was associated with increased risk of solid malignancies (RR = 1.23; 95% CI, 1.11 to 1.37). Risks were increased for uterine cancer (RR = 1.55; 95% CI, 1.03 to 2.32) and nonsignificantly for cancers of the salivary gland (RR = 2.15; 95% CI, 0.91 to 5.08), stomach (RR = 1.61; 95% CI, 0.70 to 3.69), lung (RR = 1.42; 95% CI, 0.97 to 2.08), and female breast (RR = 1.18; 95% CI, 0.99 to 1.40). Risks of total solid and female breast cancer, the most common cancer type, were highest among ≥ 20-year DTC survivors (RR
= 1.47; 95% CI, 1.24 to 1.74; RR
= 1.46; 95% CI, 1.10 to 1.95). Among 32,171 ≥ 2-year survivors, RAI was associated with increased risk of hematologic malignancies (RR = 1.51; 95% CI, 1.08 to 2.01), including leukemia (RR = 1.92; 95% CI, 1.04 to 3.56). We estimated that 6% of solid and 14% of hematologic malignancies in pediatric and young adult DTC survivors may be attributable to RAI.
In addition to leukemia, RAI treatment for childhood and young-adulthood DTC was associated with increased risks of several solid cancers, particularly more than 20 years after exposure, supporting the need for long-term surveillance of these patients.
In response to evidence of overdiagnosis and overtreatment of papillary thyroid carcinoma (PTC), the 2009 and 2015 American Thyroid Association (ATA) adult guidelines recommended less extensive ...surgery (lobectomy vs. total thyroidectomy) and more restricted use of postsurgical radioactive iodine (RAI) in management of PTC at low risk of recurrence. In 2015, active surveillance was suggested as a viable option for some <1-cm PTCs, or microcarcinomas. The 2015 ATA pediatric guidelines similarly shifted toward more restricted use of RAI for low-risk PTCs. The impact of these recommendations on low-risk adult and pediatric PTC management remains unclear, particularly after 2015.
Using data from 18 Surveillance, Epidemiology, and End Results (SEER) U.S. registries (2000-2018), we described time trends in reported first-course treatment (total thyroidectomy alone, total thyroidectomy+RAI, lobectomy, no surgery, and other/unknown) for 105,483 patients diagnosed with first primary localized PTC (without nodal/distant metastases), overall and by demographic and tumor characteristics.
The declining use of RAI represented the most pronounced change in management of PTCs <4 cm (44-18% during the period 2006-2018), including microcarcinomas (26-6% during the period 2007-2018). In parallel, an increasing proportion of PTCs were managed with total thyroidectomy alone (35-54% during the period 2000-2018), while more subtle changes were observed for lobectomy (declining from 23% to 17% during the period 2000-2006, stabilizing, and then rising from 17% to 24% during the period 2015-2018). Use of nonsurgical management did not meaningfully change over time, impacting <1% of microcarcinomas annually during the period 2000-2018. Similar treatment trends were observed by sex, age, race/ethnicity, metropolitan vs. nonmetropolitan residence, and insurance status. For pediatric patients (<20 years), use of RAI peaked in 2009 (59%), then decreased markedly to 11% (2018), while use of total thyroidectomy alone and, to a lesser extent, lobectomy increased. No changing treatment trends were observed for ≥4-cm PTCs.
The declining use of RAI in management of low-risk adult and pediatric PTC is consistent with changing recommendations from the ATA practice guidelines. Post-2015 trends in use of lobectomy and nonsurgical management of low-risk PTCs, particularly microcarcinomas, were more subtle than expected; however, these trends may change as evidence regarding their safety continues to emerge.
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