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Genicular artery embolization (GAE) is an emerging, minimally invasive therapy to address the global burden of knee osteoarthritis (OA) and the unmet needs for medically refractory disease. Although total knee arthroplasty has been a standard intervention for severe cases, GAE is developing into a promising alternative, particularly for patients ineligible for or unwilling to undergo surgery. GAE targets the inflammatory cascade underlying OA pathophysiology by arresting neoangiogenesis and preventing pathological neoinnervation, offering potential pain relief. Although early studies have established safety and short-term effectiveness, ensuing studies are needed to validate long-term safety, durability, and comparative effectiveness and to optimize patient selection, embolic agent selection, and administration techniques. Standardized reporting guidelines are therefore essential to enhance transparency and reproducibility across clinical trials, facilitating data aggregation and comparison. This Society of Interventional Radiology (SIR)–endorsed reporting standards consensus document provides a framework to harmonize future research efforts and to improve the interpretation of outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

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Purpose: Currently, there are about 15 ongoing clinical studies on low dose radiation therapy for Coronavirus Disease 2019 pneumonia. One of the underlying assumptions is that irradiation of 0.5 to 1.5 Gy is effective at ameliorating viral pneumonia. We aimed to reanalyze all available experimental radiobiologic data to assess evidence for such amelioration.Methods and Materials: With standard statistical survival models, and based on a systematic literature review, we reanalyzed 13 radiobiologic animal data sets published in 1937 to 1973 in which animals (guinea pigs/dogs/cats/rats/mice) received radiation before or after bacterial or viral inoculation, and assessing various health endpoints (mortality/pneumonia morbidity). In most data sets absorbed doses did not exceed 7 Gy.Results: For 6 studies evaluating postinoculation radiation exposure (more relevant to low dose radiation therapy for Coronavirus Disease 2019 pneumonia) the results are heterogeneous, with one study showing a significant increase (P < .001) and another showing a significant decrease (P < .001) in mortality associated with radiation exposure. Among the remaining 4 studies, mortality risk was nonsignificantly increased in 2 studies and nonsignificantly decreased in 2 others (P > .05). For preinoculation exposure the results are also heterogeneous, with 6 (of 8) data sets showing a significant increase (P < .01) in mortality risk associated with radiation exposure and the other 2 showing a significant decrease (P < .05) in mortality or pneumonitis morbidity risk.Conclusions: These data do not provide support for reductions in morbidity or mortality associated with postinfection radiation exposure. For preinfection radiation exposure the inconsistency of direction of effect is difficult to interpret. One must be cautious about adducing evidence from such published reports of old animal data sets. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effects of sublingual glyceryl trinitrate (GTN) on the quality of planning computed tomography (CT) angiography performed prior to prostate artery embolization (PAE).Materials and Methods: A retrospective cohort study was performed on patients who had previously undergone CT angiography before a procedure for PAE at our institution. Early CT angiography studies for PAE at our single center had initially been performed without GTN. These were compared to subsequent CT angiography studies that had been performed with GTN, after a previously implemented change in practice. Prostate arteries were examined by 2 blinded observers for peak enhancement (Hounsfield units [HU]) and lumen diameter. In addition, assessors' interpretation of the prostate artery origin from CT angiography was compared with the true anatomy demonstrated at the time of procedure.Results: A total of 16 patients, corresponding to 32 prostate arteries, were examined on CT angiography. Mean diameter of the prostate artery was found to be significantly greater in those receiving GTN (2.2 mm vs. 1.6 mm, P < .001). Peak prostate artery enhancement was also greater in the GTN group (218 HU vs 173 HU, P = 0.042). Observers correctly identified the prostate artery origin more frequently in the GTN group; however, this difference was not statistically significant (56% vs 25%, odds ratio = 3.9, P = .149).Conclusions: The administration of sublingual GTN immediately prior to CT angiography is associated with a significant increase in prostate artery diameter and peak opacification. This was not associated with a statistically significant increase in the ability of observers to correctly identify the origin of the prostate artery. [ABSTRACT FROM AUTHOR]

Osteoarthritis of the knee poses an ever-expanding healthcare challenge worldwide. Current treatments include conservative methods such as weight loss, pharmacological treatments including NSAIDs, and surgical techniques including total knee arthroplasty. Although frequently successful, contraindications and failure of pharmacological agents leave many, especially with mild-moderate disease, without effective treatment. Genicular artery embolization is an interventional radiology technique being developed to fill this treatment gap. For this procedure to become established, the literature must provide evidence of its underlying scientific principles, safety, efficacy and economic viability. Pathological investigation of osteoarthritis reveals that low-level inflammation plays a crucial role in disease development. Joint inflammation stimulates neoangiogenesis and accompanying neuronal growth, with the degree of microvascular invasion being correlated with more severe pain in animal models. These neovessels provide a target for embolization however, the microscopic effects of this intervention are yet to be elucidated. The side effects of GAE have been extensively investigated with no severe adverse events being recorded. Skin discoloration and puncture site hematoma are the most common, occurring in 10%-65% and 0%-17% of patients respectively. The literature also discusses ways to minimize these events. Phase one studies provide promising evidence of efficacy, demonstrating an 80% improvement in Visual Analogue Scale (VAS) and a mean difference of 36.8 in Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores at 24-months. These positive signals are also supported by a single randomized control trial. A single study has been completed regarding the cost of GAE, however further work is needed. The GAE literature demonstrates a safe procedure with promising initial evidence of efficacy. Future work should further elucidate the pathology of osteoarthritis and ways in which embolization modifies this process, alongside providing further randomized control evidence that aligns with the recommendations from the National Institute for Health and Care Excellence. The future of GAE is exciting! [ABSTRACT FROM AUTHOR]

Exposure to therapeutic doses of ionizing radiation is associated with damage to the heart and coronary arteries. However, only recently have studies with high-quality individual dosimetry data allowed this risk to be quantified while also adjusting for concomitant chemotherapy, and medical and lifestyle risk factors. At lower levels of exposure the evidence is less clear. In this article I review radiation-associated risks of circulatory disease in groups treated with radiotherapy for malignant and non-malignant disease, and in occupationally- or environmentally-exposed groups receiving rather lower levels of radiation dose, also for medical diagnostic purposes. Results of a meta-analysis suggest that excess relative risks per unit dose for various types of heart disease do not exhibit statistically significant ( p > 0.2) heterogeneity between studies. Although there are no marked discrepancies between risks derived from the high-dose therapeutic and medical diagnostic studies and from the moderate/low dose occupational and environmental studies, at least for ischemic heart disease and stroke there are indications of larger risks per unit dose for lower dose rate and fractionated exposures. Risks for stroke and other types of circulatory disease are significantly more variable ( p < 0.0001), possibly resulting from confounding and effect-modification by well known (but unobserved) risk factors. Adjustment for any of mean dose, dose fractionation or age at exposure results in the residual heterogeneity for cerebrovascular disease becoming non-significant. The review provides strong evidence in support of a causal association between both low and high dose radiation exposure and most types of circulatory disease. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether technical difficulty of computed tomography (CT)-guided percutaneous lung tumor thermal ablations is altered with the use of high-frequency jet ventilation (HFJV) under general anesthesia (GA) compared with procedures performed with normal respiration (NR) under conscious sedation (CS). Materials and Methods: Thermal ablation treatment sessions performed with NR under CS or HFJV under GA with available anesthesia records and CT fluoroscopic images were retrospectively reviewed; 13 and 33 treatment sessions, respectively, were identified. One anesthesiologist determined the choice of anesthesiologic technique independently. Surrogate measures of procedure technical difficulty--time duration, number of CT fluoroscopic acquisitions, and radiation dose required for applicator placement for each tumor--were compared between anesthesiologic techniques. The anesthesiologist time and complications were also compared. Parametric and nonparametric data were compared by Student independent-samples t test and χ(2) test, respectively. Results: Patients treated with HFJV under GA had higher American Society of Anesthesiologists classifications (mean, 2.66 vs 2.23; P = .009) and smaller lung tumors (16.09 mm vs 27.38 mm; P = .001). The time duration (220.30 s vs 393.94 s; P = .008), number of CT fluoroscopic acquisitions (10.31 vs 19.13; P = .023), and radiation dose (60.22 mGy·cm vs 127.68 mGy·cm; P = .012) required for applicator placement were significantly lower in treatment sessions performed with HFJV under GA. There was no significant differences in anesthesiologist time (P = .20), rate of pneumothorax (P = .62), or number of pneumothoraces requiring active treatment (P = .19). Conclusions: HFJV under GA appears to reduce technical difficulty of CT-guided percutaneous applicator placement for lung tumor thermal ablations, with similar complication rates compared with treatment sessions performed with NR under CS. The technique is safe and may facilitate treatment of technically challenging tumors. [ABSTRACT FROM AUTHOR]

• There is mounting evidence of cancer risk from low dose radiation in childhood. • A systematic review was conducted of cancer after exposure in utero or childhood. • There were excess cancer risks associated with radiation exposure in childhood. • There were excess cancer risks associated with radiation exposure in utero. • Excess cancer risks were seen at levels approaching 0.02 Gy. The detrimental health effects associated with the receipt of moderate (0.1–1 Gy) and high (>1 Gy) acute doses of sparsely ionising radiation are well established from human epidemiological studies. There is accumulating direct evidence of excess risk of cancer in a number of populations exposed at lower acute doses or doses received over a protracted period. There is evidence that relative risks are generally higher after radiation exposures in utero or in childhood. We reviewed and summarised evidence from 60 studies of cancer or benign neoplasms following low- or moderate-level exposure in utero or in childhood from medical and environmental sources. In most of the populations studied the exposure was predominantly to sparsely ionising radiation, such as X-rays and gamma-rays. There were significant (p < 0.001) excess risks for all cancers, and particularly large excess relative risks were observed for brain/CNS tumours, thyroid cancer (including nodules) and leukaemia. Overall, the totality of this large body of data relating to in utero and childhood exposure provides support for the existence of excess cancer and benign neoplasm risk associated with radiation doses < 0.1 Gy, and for certain groups exposed to natural background radiation, to fallout and medical X-rays in utero , at about 0.02 Gy. [ABSTRACT FROM AUTHOR]

Abstract: In this article we review health effects in offspring of human populations exposed as a result of radiotherapy and some groups exposed to chemotherapy. We also assess risks in offspring of other radiation-exposed groups, in particular those of the Japanese atomic bomb survivors and occupationally and environmentally exposed groups. Experimental findings are also briefly surveyed. Animal and cellular studies tend to suggest that the irradiation of males, at least at high doses (mostly 1Gy and above), can lead to observable effects (including both genetic and epigenetic) in the somatic cells of their offspring over several generations that are not attributable to the inheritance of a simple mutation through the parental germline. However, studies of disease in the offspring of irradiated humans have not identified any effects on health. The available evidence therefore suggests that human health has not been significantly affected by transgenerational effects of radiation. It is possible that transgenerational effects are restricted to relatively short times post-exposure and in humans conception at short times after exposure is likely to be rare. Further research that may help resolve the apparent discrepancies between cellular/animal studies and studies of human health are outlined. [Copyright &y& Elsevier]

Purpose: To assess the shape of the dose response for various cancer endpoints and modifiers by age and time. Methods and Materials: Reanalysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by cancer endpoint (stomach, pancreas, lung, leukemia, all other). Results: There are statistically significant (P<.05) excess risks for all cancer and for lung cancer and borderline statistically significant risks for stomach cancer (P=.07), and leukemia (P=.06), with excess relative risks Gy−1 of 0.024 (95% confidence interval [CI] 0.011, 0.039), 0.559 (95% CI 0.221, 1.021), 0.042 (95% CI −0.002, 0.119), and 1.087 (95% CI −0.018, 4.925), respectively. There is statistically significant (P=.007) excess risk of pancreatic cancer when adjusted for dose-response curvature. General downward curvature is apparent in the dose response, statistically significant (P<.05) for all cancers, pancreatic cancer, and all other cancers (ie, other than stomach, pancreas, lung, leukemia). There are indications of reduction in relative risk with increasing age at exposure (for all cancers, pancreatic cancer), but no evidence for quadratic variations in relative risk with age at exposure. If a linear-exponential dose response is used, there is no significant heterogeneity in the dose response among the 5 endpoints considered or in the speed of variation of relative risk with age at exposure. The risks are generally consistent with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers. Conclusions: There are excess risks for various malignancies in this data set. Generally there is a marked downward curvature in the dose response and significant reduction in relative risk with increasing age at exposure. The consistency of risks with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure. [Copyright &y& Elsevier]

Purpose: To assess the shape of the dose–response for various circulatory disease endpoints, and modifiers by age and time since exposure. Methods and Materials: This was an analysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by circulatory disease endpoint (ischemic heart, cerebrovascular, other circulatory disease). Results: There were significant excess risks for all circulatory disease, with an excess relative risk Gy−1 of 0.082 (95% CI 0.031–0.140), and ischemic heart disease, with an excess relative risk Gy−1 of 0.102 (95% CI 0.039–0.174) (both p = 0.01), and indications of excess risk for stroke. There were no statistically significant (p > 0.2) differences between risks by endpoint, and few indications of curvature in the dose–response. There were significant (p < 0.001) modifications of relative risk by time since exposure, the magnitude of which did not vary between endpoints (p > 0.2). Risk modifications were similar if analysis was restricted to patients receiving radiation, although the relative risks were slightly larger and the risk of stroke failed to be significant. The slopes of the dose–response were generally consistent with those observed in the Japanese atomic bomb survivors and in occupationally and medically exposed groups. Conclusions: There were excess risks for a variety of circulatory diseases in this dataset, with significant modification of risk by time since exposure. The consistency of the dose–response slopes with those observed in radiotherapeutically treated groups at much higher dose, as well as in lower dose–exposed cohorts such as the Japanese atomic bomb survivors and nuclear workers, implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure. [Copyright &y& Elsevier]

Abstract: Natural sources contribute a large fraction of the radiation exposure of the general public. Under the linear no-threshold hypothesis risk decreases in proportion to decreasing dose without a threshold. We use recent estimates of doses to the red bone marrow to calculate the number and proportion of cases of leukemia in England induced by natural radiation. We calculate that about 5% of cases of leukemia, excluding chronic lymphocytic leukemia, up to the age of 80 years are induced by this background radiation. In young people up to the age of 25 years the attributable fraction is about 15%, substantially lower than a previous estimate. [Copyright &y& Elsevier]

Abstract: Passive air sampling (PAS) was employed to study the occurrence of gaseous and particle-bound PAHs in the North Chinese Plain. The averaged concentrations of gaseous and particle-bound PAHs were 485±209ng/m3 and 267±161ng/m3, respectively. The PAHs concentrations at urban sites were generally higher than those at rural ones with ratios <1.5 in spring, summer and fall, but differences between them were not significant for the wintertime and annually averaged concentrations. This urban–rural distribution pattern was related to the PAHs emission sources. PAHs spatial variation can be partially (49%) explained by emission with a simple linear regression method. Both the gaseous and particle-bound PAHs were highest in winter and lowest in summer, with winter/summer ratios of 1.8 and 8, respectively. Emission strength was the most important factor for the seasonality. [Copyright &y& Elsevier]

• Ionizing radiation causes adverse circulatory and metabolic effects at high doses. • Low-dose radiation is causally associated with circulatory disease. • Impact of low-dose radiation is modulated by inflammatory, stress, and immune responses. Risks to health are the prime consideration in all human situations of ionizing radiation exposure and therefore of relevance to radiation protection in all occupational, medical, and public exposure situations. Over the past few decades, advances in therapeutic strategies have led to significant improvements in cancer survival rates. However, a wide range of long-term complications have been reported in cancer survivors, in particular circulatory diseases and their major risk factors, metabolic diseases. However, at lower levels of exposure, the evidence is less clear. Under real-life exposure scenarios, including radiotherapy, radiation effects in the whole organism will be determined mainly by the response of normal tissues receiving relatively low doses, and will be mediated and moderated by systemic effects. Therefore, there is an urgent need for further research on the impact of low-dose radiation. In this article, we review radiation-associated risks of circulatory and metabolic diseases in clinical, occupational or environmental exposure situations, addressing epidemiological, biological, risk modelling, and systems biology aspects, highlight the gaps in knowledge and discuss future directions to address these gaps. [ABSTRACT FROM AUTHOR]

Glaucoma is a group of optic neuropathies causing optic nerve damage and visual field defects, and is one of the leading causes of blindness. Nearly a century has passed since the first report of glaucoma manifested following ionizing radiation therapy of cancers. Nevertheless, associations between glaucoma and radiation exposures, a dose response relationship, and the mechanistic underpinnings remain incompletely understood. Here we review the current knowledge on manifestations and mechanisms of radiogenic glaucoma. There is some evidence that neovascular glaucoma is manifest relatively quickly, within a few years after high-dose and high dose-rate radiotherapeutic exposure, but little evidence of excess risks of glaucoma after exposure to much lower doses or dose rates. As such, glaucoma appears to have some of the characteristics of a tissue reaction effect, with a threshold of at least 5 Gy but possibly much higher. [ABSTRACT FROM AUTHOR]

A response by Mark P. Little and Paul Elliot to a letter to the editor about their article "Hemoglobin concentration in pregnancy and perinatal mortality: a London-based cohort study," which was published in the previous issue of the journal is presented.

We demonstrate a strong correlation between domestic radon levels and socio-economic status (SES) in Great Britain, so that radon levels in homes of people with lower SES are, on average, only about two thirds of those of the more affluent. This trend is apparent using small area measures of SES and also using individual social classes. The reasons for these differences are not known with certainty, but may be connected with greater underpressure in warmer and better-sealed dwellings. There is also a variation of indoor radon levels with the design of the house (detached, terraced, etc.). In part this is probably an effect of SES, but it appears to have other causes as well. Data from other countries are also reviewed, and broadly similar effects seen in the United States for SES, and in other European countries for detached vs other types of housing. Because of correlations with smoking, this tendency for the lower SES groups to experience lower radon levels may underlie the negative association between radon levels and lung cancer rates in a well-known ecological study based on US Counties. Those conducting epidemiological studies of radon should be alert for this effect and control adequately for SES. [ABSTRACT FROM AUTHOR]

It is well established that high-dose ionising radiation causes cardiovascular diseases. In contrast, the evidence for a causal relationship between long-term risk of cardiovascular diseases after moderate doses (0.5–5 Gy) is suggestive and weak after low doses (<0.5 Gy). However, evidence is emerging that doses under 0.5 Gy may also increase long-term risk of cardiovascular disease. This would have major implications for radiation protection with respect to medical use of radiation for diagnostic purposes and occupational or environmental radiation exposure. Therefore, it is of great importance to gain information about the presence and possible magnitude of radiation-related cardiovascular disease risk at doses of less than 0.5 Gy. The biological mechanisms implicated in any such effects are unclear and results from epidemiological studies are inconsistent. Molecular epidemiological studies can improve the understanding of the pathogenesis and the risk estimation of radiation-induced circulatory disease at low doses. Within the European DoReMi (Low Dose Research towards Multidisciplinary Integration) project, strategies to conduct molecular epidemiological studies in this field have been developed and evaluated. Key potentially useful European cohorts are the Mayak workers, other nuclear workers, uranium miners, Chernobyl liquidators, the Techa river residents and several diagnostic or low-dose radiotherapy patient cohorts. Criteria for informative studies are given and biomarkers to be investigated suggested. A close collaboration between epidemiology, biology and dosimetry is recommended, not only among experts in the radiation field, but also those in cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Rapid innovations in radiation therapy techniques have resulted in an urgent need for risk projection models for second cancer risks from high-dose radiation exposure, because direct observation of the late effects of newer treatments will require patient follow-up for a decade or more. However, the patterns of cancer risk after fractionated high-dose radiation are much less well understood than those after lower-dose exposures (0.1-5 Gy). In particular, there is uncertainty about the shape of the dose-response curve at high doses and about the magnitude of the second cancer risk per unit dose. We reviewed the available evidence from epidemiologic studies of second solid cancers in organs that received high-dose exposure (>5 Gy) from radiation therapy where dose-response curves were estimated from individual organ-specific doses. We included 28 eligible studies with 3434 second cancer patients across 11 second solid cancers. Overall, there was little evidence that the dose-response curve was nonlinear in the direction of a downturn in risk, even at organ doses of ≥60 Gy. Thyroid cancer was the only exception, with evidence of a downturn after 20 Gy. Generally the excess relative risk per Gray, taking account of age and sex, was 5 to 10 times lower than the risk from acute exposures of <2 Gy among the Japanese atomic bomb survivors. However, the magnitude of the reduction in risk varied according to the second cancer. The results of our review provide insights into radiation carcinogenesis from fractionated high-dose exposures and are generally consistent with current theoretical models. The results can be used to refine the development of second solid cancer risk projection models for novel radiation therapy techniques. [ABSTRACT FROM AUTHOR]

Abstract: Non-DNA targeted effects of ionising radiation, which include genomic instability, and a variety of bystander effects including abscopal effects and bystander mediated adaptive response, have raised concerns about the magnitude of low-dose radiation risk. Genomic instability, bystander effects and adaptive responses are powered by fundamental, but not clearly understood systems that maintain tissue homeostasis. Despite excellent research in this field by various groups, there are still gaps in our understanding of the likely mechanisms associated with non-DNA targeted effects, particularly with respect to systemic (human health) consequences at low and intermediate doses of ionising radiation. Other outstanding questions include links between the different non-targeted responses and the variations in response observed between individuals and cell lines, possibly a function of genetic background. Furthermore, it is still not known what the initial target and early interactions in cells are that give rise to non-targeted responses in neighbouring or descendant cells. This paper provides a commentary on the current state of the field as a result of the non-targeted effects of ionising radiation (NOTE) Integrated Project funded by the European Union. Here we critically examine the evidence for non-targeted effects, discuss apparently contradictory results and consider implications for low-dose radiation health effects. [Copyright &y& Elsevier]