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Objectives: Olfactory dysfunction is an overlooked adverse effect of radiation therapy. This study is designed to find the effect of radiation therapy on olfactory function in head and neck malignancy excluding tumors of nose and nasopharynx and correlate the olfactory changes with the radiotherapy dose., Method: This prospective observational study was done over a 2-year period in 34 participants with head and neck malignancies who underwent radiation therapy (RT). The participants olfaction was evaluated subjectively with Italian Nose Obstruction Symptom Evaluation (I-NOSE) scale and objectively by a modified I-Smell test which included an olfactory identification score and an olfactory threshold score at 5 time points. The beginning of RT ( T 0), at 2 weeks of RT( T 1), end of RT ( T 2), 1 month follow-up ( T 3), and 3-month follow-up ( T 4). The near maximum dose to the nasal cavity ( D 2% ) and mean dose to the nasal cavity ( D mean ) were calculated for all participants and correlated with olfactory function., Results: A total of 34 patients with head neck malignancy were recruited. The median I-NOSE score reached maximum at the end of radiation and decreased to baseline at 3 months follow-up ( P  < .001). The olfactory identification score, olfactory threshold score, and median combined olfactory score showed a significant decrease at the end of radiation therapy compared to Pre-radiation therapy values. There was a significant but incomplete recovery in the 3-month follow-up period ( P  < .001)., Conclusion: There was a significant deterioration in quality of life for olfaction, olfactory identification, and olfactory threshold at the completion of radiotherapy. At 3 months follow-up, though there was no complete recovery of olfaction, it did not have an adverse effect on the quality of life., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Oxidative stress results from the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in quantities exceeding the potential activity of the body's antioxidant system and is one of the risk factors for the development of vascular dysfunction in diabetes and exposure to ionizing radiation. Being the secondary products of normal aerobic metabolism in living organisms, ROS and RNS act as signaling molecules that play an important role in the regulation of vital organism functions. Meanwhile, in high concentrations, these compounds are toxic and disrupt various metabolic pathways. The various stress factors (hyperglycemia, gamma-irradiation, etc.) trigger free oxygen and nitrogen radicals accumulation in cells that are capable to damage almost all cellular components including ion channels and transporters such as Na + /K + -ATPase, BK Ca , and TRP channels. Vascular dysfunctions are governed by interaction of ROS and RNS. For example, the reaction of ROS with NO produces peroxynitrite (ONOO - ), which not only oxidizes DNA, cellular proteins, and lipids, but also disrupts important signaling pathways that regulate the cation channel functions in the vascular endothelium. Further increasing in ROS levels and formation of ONOO - leads to reduced NO bioavailability and causes endothelial dysfunction. Thus, imbalance of ROS and RNS and their affect on membrane ion channels plays an important role in the pathogenesis of vascular dysfunction associated with various disorders., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The cardiac toxicity of radiotherapy (RT) can affect cancer survival rates over the long term. This has been confirmed in patients with breast cancer and lymphoma. However, there are few studies utilizing the two-dimensional speckle-tracking echocardiography (2D-STE) to evaluate the risk factors affecting radiation induced heart disease (RIHD), and there is a lack of quantitative data. Therefore, we intend to explore the risk factors for RIHD and quantify them using 2D-STE technology., Methods: We ultimately enrolled 40 patients who received RT for thoracic tumors. For each patient, 2D-STE was completed before, during, and after RT and in the follow up. We analyzed the sensitivity of 2D-STE in predicting RIHD and the relationship between RT parameters and cardiac systolic function decline., Results: Left ventricle global longitudinal strain (LVGLS), LVGLS of the endocardium (LVGLS-Endo), LVGLS of the epicardium (LVGLS-Epi), and right ventricle free-wall longitudinal strain (RVFWLS) decreased mid- and post-treatment compared with pre-treatment, whereas traditional parameters such as left ventricular ejection fraction (LVEF), cardiac Tei index (Tei), and peak systolic velocity of the free wall of the tricuspid annulus (s') did not show any changes. The decreases in the LVGLS and LVGLS-Endo values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with mean heart dose (MHD) (all P values < 0.05). The decreases in the LVGLS-Epi values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with the percentage of heart volume exposed to 5 Gy or more (V5) (P values < 0.05). The decrease in RVFWLS and the ratio of the decrease to the baseline value were linearly related to MHD and patient age (all P values < 0.05). Endpoint events occurred more frequently in the right side of the heart than in the left side. Patients over 56.5 years of age had a greater probability of developing right-heart endpoint events. The same was true for patients with MHD over 20.2 Gy in both the left and right sides of the heart., Conclusions: 2D-STE could detect damages to the heart earlier and more sensitively than conventional echocardiography. MHD is an important prognostic parameter for LV systolic function, and V5 may also be an important prognostic parameter. MHD and age are important prognostic parameters for right ventricle systolic function., (© 2024. The Author(s).)

Purpose: The most prevalent lacrimal apparatus dysfunctions associated with differentiated thyroid cancer(DTC) after I-131 therapy are dry eye and nasolacrimal duct obstruction(NLDO), leading to ocular discomfort and lower quality of life for patients. It is crucial to diagnose and manage lacrimal apparatus dysfunction associated with I-131 therapy for DTC. Therefore, this review aims to comprehensively summarize and analyze the advances in mechanisms and therapeutic options underlying lacrimal apparatus dysfunction induced by I-131 therapy for DTC., Methods: A comprehensive search of CNKI, PubMed, and Wed of Science was performed from the database to December of 2023. Key search terms were "Thyroid cancer", "I-131", "Complications", "Dry eye", "Epiphora", "Tear", "Nasolacrimal duct" and "NLDO"., Results: The research indicates that I-131 therapy for DTC causes damage to the lacrimal glands and nasolacrimal duct system, resulting in symptoms such as dry eye, epiphora, and mucoid secretions. Moreover, recent research has focused on exploring relevant risk factors of the condition and experimental and clinical treatments. However, there is some controversy regarding the mechanisms involved, whether it is due to the passive flow of I-131 in tears, active uptake of I-131 by the sodium-iodide symporter (NIS) in the lacrimal sac and nasolacrimal duct, or secondary metabolic and hormonal disturbances caused by I-131., Conclusion: It is crucial for early detection and preventive measures by ophthalmologists and the need for further studies to elucidate the mechanisms underlying the disease., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: We used electromyography to characterize hypoglossal nerve function among radiation-treated head and neck cancer survivors with later onset unilateral tongue immobility., Methods: Patients with unilateral tongue immobility without evidence of recurrent cancer were seen at a tertiary academic institution between February and September 2021. All patients were at least 2 years post-treatment with radiation therapy for head and neck squamous cell carcinoma. Participants were under annual surveillance and displayed no evidence of operative injury to the hypoglossal nerve., Results: The median symptom-free interval for the 10 patients included in this study was 13.2 years (range 2-25 years). Myokymia alone was present in 3 of 10 patients, fibrillation potentials alone were present in 3 of 10 patients, and 1 subject displayed both fibrillation and myokymia. Three out of 10 patients had normal hypoglossal nerve function., Discussion: These findings highlight how disparate mechanisms may underlie similar clinical presentations of radiation-induced neuromuscular dysfunction., (© 2024 Wiley Periodicals LLC.)

Over the years, the advancement of radio diagnostic imaging tools and techniques has radically improved the diagnosis of different pathophysiological conditions, accompanied by increased exposure to low-dose ionizing radiation. Though the consequences of high dose radiation exposure on humans are very well comprehended, the more publicly relevant effects of low dose radiation (LDR) (≤100 mGy) exposure on the biological system remain ambiguous. The central nervous system, predominantly the developing brain with more neuronal precursor cells, is exceptionally radiosensitive and thus more liable to neurological insult even at low doses, as shown through several rodent studies. Further molecular studies have unraveled the various inflammatory and signaling mechanisms involved in cellular damage and repair that drive these physiological alterations that lead to functional alterations. Interestingly, few studies also claim that LDR exerts therapeutic effects on the brain by initiating an adaptive response. The present review summarizes the current understanding of the effects of low dose radiation at functional, cellular, and molecular levels and the various risks and benefits associated with it based on the evidence available from in vitro, in vivo, and clinical studies. Although the consensus indicates minimum consequences, the overall evidence suggests that LDR can bring about considerable neurological effects in the exposed individual, and hence a re-evaluation of the LDR usage levels and frequency of exposure is required., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The review is devoted to long-term genetic and epigenetic disorders in exposed individuals and their descendants,namely to cytogenetic effects in the Chornobyl NPP accident clean-up workers and their children, DNA methylation as an epigenetic modification of human genome. Data presented in review expand the understanding of risk of the prolonged exposure for the present and future generations, which is one of key problems posed by fundamental radiation genetics and human radiobiology., (O. V. Kucher, S. V. Vydyborets.)

The review is devoted to the summarizing of 35 years of research of ionizing radiation exposure and radionuclidesinhalation influence on the bronchopulmonary system of clean-up workers of the Chornobyl NPP accident. Radiationand hygienic preconditions for the formation of chronic respiratory pathology are considered, taking into accountthe dosimetric data of irradiation of the bronchopulmonary system.The main clinical symptoms, features of disorders of pulmonary ventilation capacity and endoscopic forms of lesionsof the bronchopulmonary system of participants in the liquidation of the accident were determined.On the basis of pathomorphological, microbiological and immunological researches the pathomorphosis of chronicnonspecific lung diseases in the conditions of the Chernobyl catastrophe is proved.It is proved that under combined influence of external irradiation and inhalation of a fragmentary mixture ofradionuclides in the condition of the Chernobyl catastrophe, the bronchopulmonary system has become one of themain «targets»-tissues, of realization of stochastic and nonstochastic effects., (V. O. Sushko, L. I. Shvaiko, K. D. Bazyka, O. V. Apostolova, O. O. Kolosynska.)

Purpose: To investigate macular microvascular characteristics imaged by optical coherence tomography angiography in patients with uveal melanoma following conbercept injections after plaque radiotherapy., Methods: Prospective comparative analysis comprising 15 patients with uveal melanoma with conbercept injections and 30 patients without conbercept injections after plaque radiotherapy by optical coherence tomography angiography. The conbercept group received intravitreal conbercept injections at the time of plaque removal, 1 month, 3 months, 6 months , 9 months and 12 months after plaque removal (total, 6 injections). The control group had no intravitreal conbercept injection., Results: After initiation of conbercept injections, superficial retinal vascular density in the whole image and parafoveal region were significantly higher at 6 months, whereas there was no significant difference at 9 months and 12 months. In analysis of variance analysis, superficial retinal vascular density in the whole image remained stable after conbercept injections (P = 0.069), whereas the superficial retinal vascular density decreased significantly after plaque radiotherapy in the control group (P = 0.011). In multivariable linear regression, a higher superficial retinal vascular density in the whole image region at 6 months was significantly associated with intravitreal conbercept injection (P = 0.018), wider tumor base (P = 0.026), and thinner tumor thickness (P = 0.04)., Conclusion: Optical coherence tomography angiography can provide a quantitative evaluation of early retinal microvascular changes after radiotherapy. Intravitreal conbercept treatment could partly relieve the retinal vascular damage in response to radiation therapy at early stage in patients with uveal melanoma; however, it may not be able to provide long-term positive functional outcomes., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Objective: to investigate the clinical, hormonal-metabolic and structural features of parathyroid injuries in sur-vivors exposed to ionizing radiation after the Chornobyl NPP accident in adulthood and childhood, both with theirconnections to other non-cancerous endocrine disorders, and to establish the respective interhormonal and dys-metabolic relationships., Materials and Methods: Clinical effects of ionizing radiation on the endocrine system in persons affected by theChornobyl NPP accident (n = 224) and their descendants (n = 146), compared with the general population sample(n = 70) were the study object. All patients underwent the ultrasound thyroid and parathyroid examination. Thegenerally recognized clinical, anthropometric (body weight, height, thigh volume, body mass index), instrumental(ultrasound examination of thyroid and parathyroid glands), laboratory (biochemical, hormonal), and statisticalmethods were applied. Parametric and nonparametric statistical methods were used in data processing. The value ofp < 0.05 was considered a statistically significant., Results: No significant difference was found in the incidence of carbohydrate metabolic disorders in the ChornobylNPP (ChNPP) accident consequences clean-up workers (ACCUW), evacuees from the NPP 30-km exclusion zone, res-idents of radiologically contaminated areas and in the control group in whom the parathyroid hyperplasia wasdetected. There was a significant increase in the incidence of arterial hypertension among ACCUW who had parathy-roid hyperplasia (76.9%) vs. the control group (51.2%). In cases of parathyoid hyperplasia the vitamin D levels weresignificantly lower than without it. Vitamin D insufficiency/deficiency was found in 94% of the surveyed subjects.The average level of parathyroid hormone in blood serum was significantly higher in the ACCUW of «iodine» period withdiagnosed parathyroid hyperplasia than in the control group: (57.2 ± 2.87) pg / ml against (32.74 ± 3.58) pg / ml,p < 0.05. Results of multivariative analysis indicated a strong association of vitamin 25(OH)D insufficiency/defi-ciency with development of thyroid disease, carbohydrate metabolic disorders, cardiovascular disease, osteo-penia/osteoporosis. parathyroid ultrasound scan was at that an effective diagnostic method for primary screeningfor parathyroid hyperplasia and regular monitoring of the treatment efficiency. When examining children bornto parents irradiated after the ChNPPA the parathyroid hyperplasia (58%) and low serum content of vitamin D(11.6 ± 3.5) nmol / l were most often found in children living on radiologically contaminated territories (RCT).A strong correlation was established between the HOMA insulin resistance index and serum content of vitamin D(r = 0.65), parathyroid hormone (r = 0.60), and free thyroxine (r = 0.68) in the group of children born to parents irra-diated after the ChNPPA, having got chronic autoimmune thyroiditis, which indicated a relationship between thy-roid function, impaired carbohydrate and fat metabolism and the state of parathyroids., Conclusions: No difference in the incidence of carbohydrate metabolic disorders was found in the ChNPP ACCUW,evacuees from the 30-km exclusion zone, and residents of radiologically contaminated territories in whom parathy-roid hyperplasia was detected vs. the control group. Patients with parathyroid hyperplasia were found to be defi-cient in vitamin D in 94% of cases, and level of latter was significantly lower than under the normal parathyroid size.There was a significant increase in the incidence of diagnosed arterial hypertension among ACCUW who had parathy-roid hyperplasia vs. the control group: (76.9 ± 3.5)% vs. (51.2 ± 3.7)%. According to multivariate analysis a strongassociation between the vitamin 25(OH)D insufficiency/deficiency and development of thyroid disease, carbohydratemetabolic disorders, cardiovascular disease, and osteopenia/osteoporosis was established. The average level of pa-rathyroid hormone in the blood serum of the ChNPP ACCUW of the «iodine» period with diagnosed parathyroid hyper-plasia was significantly higher (57.2 ± 2.87) pg / ml against (32.74 ± 3.58) pg / ml; p <0,05) in the control group., (O. V. Kaminskyi, O. V. Kopylova, D. E. Afanasyev, I. M. Muraviova, I. G. Chikalova, N. S. Dombrovska.)

The analysis of long-term researches of the pathological changes arising in soft tissues at patients with a breast cancer as a result of radical surgical treatment and adjuvant radiotherapy is carried out in work. The article shows that the standard approach to postoperative radiation therapy, which is based only on the prevalence of the primary tumor process is not always justified. Very often it leads to excessive radiation load on the patient's body and the development of local acute and chronic radiation reactions of the skin, subcutaneous tissue and other soft tissues.In this regard, the question of differentiated purpose of radiotherapy acquires special value first of all at patients with small primary prevalence of tumor process. The paper presents the results of studies to study changes in the anterior chest wall in patients with breast cancer. In relation to the conduct of adjuvant radiotherapy more often need to use the concept of personalized radiation therapy. Radical operation, post-radiation early and late pathological changes in soft tissues, disturbance of microcirculation of lymph and blood, disturbance of innervation of vessels of an upper extremity, peripheral nerves in system of a cervical and plexus plexus, leads to intensive degen-erative and dystrophic changes in soft tissues of the upper. and causes morphological changes in them and further progression of reflex neurovascular and neurodystrophic disorders. Based on the data of adverse effects of radio-therapy on the skin and surrounding tissues, as well as to reduce excessive radiation exposure to the patient's body, a differentiated approach to the appointment of adjuvant radiation therapy., (D. A. Bazyka, O. O. Litvinenko, S. G. Bugaytsov, G. F. Shakhrai.)

Background: Ionizing radiation (IR) can affect the brain and the visual organ even at low doses, while provoking cognitive, emotional, behavioral, and visual disorders. We proposed to consider the brain and the visual organ as potential targets for the influence of IR with the definition of cerebro-ophthalmic relationships as the «eye-brain axis»., Objective: The present work is a narrative review of current experimental, epidemiological and clinical data on radiation cerebro-ophthalmic effects in children, individuals exposed in utero, astronauts and interventional radiologists., Materials and Methods: The review was performed according to PRISMA guidelines by searching the abstract and scientometric databases PubMed/MEDLINE, Scopus, Web of Science, Embase, PsycINFO, Google Scholar, published from 1998 to 2021, as well as the results of manual search of peer-reviewed publications., Results: Epidemiological data on the effects of low doses of IR on neurodevelopment are quite contradictory, while data on clinical, neuropsychological and neurophysiological on cognitive and cerebral disorders, especially in the left, dominant hemisphere of the brain, are nore consistent. Cataracts (congenital - after in utero irradiation) and retinal angiopathy are more common in prenatally-exposed people and children. Astronauts, who carry out longterm space missions outside the protection of the Earth's magnetosphere, will be exposed to galactic cosmic radiation (heavy ions, protons), which leads to cerebro-ophthalmic disorders, primarily cognitive and behavioral disorders and cataracts. Interventional radiologists are a special risk group for cerebro-ophthalmic pathology - cognitivedeficits, mainly due to dysfunction of the dominant and more radiosensitive left hemisphere of the brain, andcataracts, as well as early atherosclerosis and accelerated aging., Conclusions: Results of current studies indicate the high radiosensitivity of the brain and eye in different contingents of irradiated persons. Further research is needed to clarify the nature of cerebro-ophthalmic disorders in different exposure scenarios, to determine the molecular biological mechanisms of these disorders, reliable dosimetric support and taking into account the influence of non-radiation risk factors., (K. M. Loganovsky, P. A. Fedirko, D. Marazziti, K. V. Kuts, K. Yu. Antypchuk, I. V. Perchuk, T. F. Babenko, T. K. Loganovska, O. O. Kolosynska, G. Yu. Kreinis, S. V. Masiuk, L. L. Zdorenko, N. A. Zdanevich, N. A. Garkava, R. Yu. Dorichevska, Z. L. Vasilenko, V. I. Kravchenko, N. V. Drosdova, Yu. V. Yefimova, A. V. Malinyak.)

Objective: to evaluate the parameters of inflammatory reaction and oxidative stress in patients with non-alcoholicfatty liver disease (NAFLD) in the remote period after the influence of the Chornobyl accident factors., Materials and Methods: Eighty two patients with NAFLD who had been exposed to ionizing radiation as a result ofthe Chornobyl accident and have concomitant cardiovascular pathology were examined. Hematological parametersand the level of highly sensitive C-reactive protein (hsCRP) were determined, and the content of products of oxida-tive modification of lipids and proteins was evaluated., Results: Activation of the processes of oxidative modification of lipids and proteins was observed in most patientswith NAFLD. According to the level of hsCRP, the presence of subclinical inflammation and the risk of developingcomplicated cardiovascular pathology was found in 58 % of patients with NAFLD. The neutrophil / lymphocyte ratiocorrelates positively with hsCRP and can be used as an available routine clinical marker for selection among patientswith NAFLD persons with increased risk of cardiovascular complications., Conclusions: HsCRP, oxidative modification products of lipids and proteins, ESR, and leukograms should be used toassess the degree of systemic inflammation in people affected by the Chornobyl accident, suffering NAFLD with con-comitant cardiovascular disease., (O. V. Nosach, E. O. Sarkissova, S. M. Alyokhina, O. Ya. Pleskach, O. M. Litvinets, L. M. Ovsyannikova, A. A. Chumak.)

Objective: to analyze comorbid pathology by methods of its quantitative assessment in servicemen exposed toextreme factors of military service (a set of factors of radiation accidents, the influence of modern armed conflictsand modern combat trauma without blood loss)., Materials and Methods: Studies of comorbid pathology were performed in 613 servicemen who were treated at theclinical base of the Ukrainian Military Medical Academy (UMMA) in National Military Medical Clinical Center «MainMilitary Clinical Hospital» NMMCC «MMCH» during 1989-2018 years. Soldiers who suffered from acute radiation sick-ness (ARS) in 1961 (n = 34), participants in the liquidation of the consequences of the Chornobyl catastrophe(PLCChC) 15 years after participating in the elimination of its consequences and in a later period (respectivelyPLCChC 1st group (n = 59) and the 2nd group (n = 337)). Soldiers are participants in the anti-terrorist operation(ATO)/Combined Forces (CFO) operation who did not receive modern combat injuries with blood loss (participants inthe ATO/CFO, n = 183). All servicemen did not have any diseases limiting their fitness capabilities for military serv-ice before being exposed to extreme factors of military service. A cumulative CIRS scale was used to comprehensive-ly assess comorbidity., Results: With increasing time after participation in the elimination of the consequences of radiation accidents, thecourse of arterial hypertension (AH) is aggravated, but the dose-dependence of the severity of AH on the receivedradiation dose has not been established. The easier course of hypertension in ATO/CFO servicemen compared to ARSremote servicemen and group 2 PLCChC servicemen can be explained by their younger age at the time of the surveyand less time after exposure to extreme military service factors. In the military in the remote period after exposureto a complex of factors of radiation accidents, the frequency of diagnosing diseases by individual organs and bodysystem increases comparing to non-irradiated servicemen. The total number of disease severity scores on the cumu-lative scale of CIRS diseases is also higher. However, a dose-dependent effect of the severity of comorbid patholo-gy was also not found. These data indicate a higher prevalence of comorbid pathology in servicemen affected by acomplex of factors of radiation accf5idents, compared with participants in the anti-terrorist operation / environ-mental protection. However, the lower severity of comorbid pathology in ATO/CFO participants can also be explainedby their younger age at the time of the survey and less time after exposure to extreme factors of military service., Conclusions: For servicemen, with increasing time after participation in the elimination of the consequences ofradiation accidents, the course of hypertension without its dose dependence becomes more difficult. The total num-ber of disease severity scores on the cumulative scale of CIRS diseases in servicemen in the remote period after participation in the elimination of the consequences of radiation accidents is higher than in non-irradiated service-men. However, a dose-dependent effect of the severity of comorbid pathology was also not found., (A. A. Voronko, O. V. Seliuk, O. V. Bohomolets.)

Objective: to establish the relationship between quantitative and qualitative parameters of peripheral blood cells(lymphocytes, neutrophilic granulocytes, monocytes, platelets) depending on the type of somatic diseases andannual internal radiation doses from 137Cs in children - residents of radiologically contaminated territories in thelate period after the Chornobyl Nuclear Power Plant (ChNPP) accident., Materials and Methods: There were 175 children included in the study comprising residents of radiologically con-taminated territories (n = 79) aged from 4 to 18 years. Annual internal radiation doses in children from 137Cs rangedfrom 0.004 to 0.067 mSv. Certain blood parameters were assessed in a comparative mode in children having got theradiation doses up to 0.01 mSv and higher. The comparison group (n = 96) included children living in settlementsnot attributed to the radiologically contaminated ones. Incidence and type of somatic diseases and its impact onquantitative and qualitative changes in blood parameters (i.e. lymphocyte, neutrophilic granulocyte, monocyte, andplatelet count) were studied. The cell size, state of nucleus, membranes and cytoplasm, signs of proliferative anddegenerative processes were taken into account., Results: Incidence and type of somatic diseases in children did not depend on the annual internal radiation dose.Number of cases of monocytosis was significantly higher among the children exposed to ionizing radiation than inthe comparison group (16.6 % vs. 7.3 %). There were, however, no correlation between these changes and radiationdoses. Number of activated blood monocytes with cytoplasmic basophilia and residues of nucleoli in nuclei washigher in individuals with internal radiation doses > 0.01 mSv. A direct correlation between the qualitative param-eters of monocytes and internal radiation doses was established (rs = 0.60; р < 0.001), as well as a direct correlationof different strength between qualitative parameters of blood cells, indicating their unidirectional pattern depend-ing on the somatic morbid conditions. Regardless of annual internal radiation dose, there was an increase in thenumber of degenerative and aberrant cells vs. the comparison group (р < 0.05), which could be due to the role ofnon-radiation factors., Conclusions: Results of the assessment of quantitative and qualitative parameters of peripheral blood cells reflect-ed the state of morbid conditions in children and are of a diagnostic value. The identified dose-dependent changesin monocyte lineage of hematopoiesis may be the markers of impact of long-term radionuclide incorporation withfood in children living in environmentally unfavorable conditions after the ChNPP accident., (V. G. Bebeshko, K. M. Bruslova, L. O. Lyashenko, T. I. Pushkariova, N. M. Tsvetkova, S. G. Galkina, V. V. Vasylenko, Zh. S. Yaroshenko, A. L. Zaitseva, L. O. Gonchar, S. M. Yatsemirskyi.)

The objective of the study was to improve the biological dosimetry approach among patients with acute radiationsickness of various degrees based on the analysis of radiation-induced chromosome aberrations in peripheral bloodlymphocytes of the victims., Materials and Methods: The study was based on primary cytogenetic data obtained in May 1986 within examina-tion of the 30 clean-up workers («liquidators») having got stage I-III acute radiation sickness. Dose verificationwas performed using the cytogenetic dosimetry based on a culture of peripheral blood lymphocytes with metaphaseanalysis of chromosome aberrations., Results: A new method of evaluating the results of patients' cytogenetic examination at the beginning of specifictherapy has been developed. Procedure was performed using a model of multiple linear regression (complex of cyto-genetic parameters) and provided a satisfactory diagnostic level (featuring a compliance with initially definedclinical and laboratory diagnoses). Overall frequency of the aberrant cells and radiation markers increased in high-er disease stages. There was a trend of the frequency growth of chromatid-type aberrations with increasing of radi-ation burden. Adequacy of the proposed method based on the regression analysis of cytogenetic results was con-firmed through the preservation of group differences in estimates of disease stage in subjects with verified diagnosis., Conclusion: Cytogenetic dosimetry in the scope of examination of persons exposed to ionizing radiation is an oblig-atory component of radiation sickness stage verification. The recommended method of cytogenetic data evaluationbefore and at the beginning of detoxification therapy provides a satisfactory level of diagnostics., (E. A. Djomina, V. V. Talko.)

Cardiotoxicity is a common side effect induced by cancer therapies, which increases the risk of long-term morbidity and mortality in cancer survivors. To date, the mechanism leading to this toxicity is still unclear, thus complicating cardiac safety assessment and predictive factor identification. The advances in technology, particularly regarding radiation therapy and constant development of novel antineoplastic agents, require urgent development of efficient preclinical models to detect drug cardiotoxicity. A myriad of empirical preclinical models have been used to investigate cardiotoxicity, though with limited success. Recently, multicellular spheroid models have gained attention by mimicking the in vivo microenvironment. The aim of this review is to focus on the most relevant preclinical models used to assess antineoplastic drug- and radiotherapy-related cardiotoxicities, with an overview on their current use. It also aims to discuss the possible directions of translational research in the cardio-oncology field., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The aim of this study was to investigate differences in reflexive and volitional cough airflows in advanced stage head and neck cancer survivors as it relates to aspiration status and time since treatment. The hypothesis is that those who aspirate several years after treatment completion would demonstrate reduced airflows for all cough parameters compared to those recently status post treatment completion given the known progressive deterioration associated with radiotherapy., Methods: Demographic and airflow data during both reflexive and volitional cough tasks and aspiration status as determined during fiberoptic endoscopic evaluation of swallow function were collected from 33 Head and Neck Cancer (HNC) survivors., Results: Omnibus MANOVA for dependent airflow variables and independent variables aspiration status, time since treatment and cough type (reflex or volitional) was significant (F(3,1) = 184, p < 0.000) indicating that peak expiratory flow rates (PEFR) were reduced under reflex (mean PEFR 1.88 SD 0.7) versus volitional (mean PEFR 2.3, SD 0.7) cough types; reduced for aspirators versus non-aspirators (F(2,1) = 4.1, p = 0.04) and reduced for those in the subacute versus chronic phase status post Intensity Modulated Radiotherapy (IMRT) (F(2,1) = 10.05, p = 0.002)., Conclusion: Findings of reduced reflexive compared to volitional cough airflows in head and neck cancer survivors are consistent with those from both healthy and other diseased populations. Additional findings that aspirators demonstrate reduced cough airflows compared to non-aspirators supports the hypothesis. Surprisingly, those recently status post treatment completion show worse cough airflows compared to those remotely status post treatment completion., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Radiation dose received by the neural stem cells of the hippocampus during whole-brain radiotherapy has been associated with neurocognitive decline. The key concern using hippocampal avoidance-prophylactic cranial irradiation (HA-PCI) in patients with small-cell lung cancer (SCLC) is the incidence of brain metastasis within the hippocampal avoidance zone., Methods: This phase III trial enrolled 150 patients with SCLC (71.3% with limited disease) to standard prophylactic cranial irradiation (PCI; 25 Gy in 10 fractions) or HA-PCI. The primary objective was the delayed free recall (DFR) on the Free and Cued Selective Reminding Test (FCSRT) at 3 months; a decrease of 3 points or greater from baseline was considered a decline. Secondary end points included other FCSRT scores, quality of life (QoL), evaluation of the incidence and location of brain metastases, and overall survival (OS). Data were recorded at baseline, and 3, 6, 12, and 24 months after PCI., Results: Participants' baseline characteristics were well balanced between the two groups. The median follow-up time for living patients was 40.4 months. Decline on DFR from baseline to 3 months was lower in the HA-PCI arm (5.8%) compared with the PCI arm (23.5%; odds ratio, 5; 95% CI, 1.57 to 15.86; P = .003). Analysis of all FCSRT scores showed a decline on the total recall (TR; 8.7% v 20.6%) at 3 months; DFR (11.1% v 33.3%), TR (20.3% v 38.9%), and total free recall (14.8% v 31.5%) at 6 months, and TR (14.2% v 47.6%) at 24 months. The incidence of brain metastases, OS, and QoL were not significantly different., Conclusion: Sparing the hippocampus during PCI better preserves cognitive function in patients with SCLC. No differences were observed with regard to brain failure, OS, and QoL compared with standard PCI., Competing Interests: Núria Rodríguez de DiosConsulting or Advisory Role: AstraZeneca SpainSpeakers' Bureau: AstraZeneca Spain, Siemens Healthineers Felipe CouñagoHonoraria: AstraZeneca, Astellas Pharma Juan Domigo GispertResearch Funding: Roche Diagnostics, GE Healthcare Jaume CapelladesTravel, Accommodations, Expenses: MedtronicNo other potential conflicts of interest were reported.

Radiation therapy (RT) is a curative treatment for many malignancies and provides effective palliation in patients with tumor-related symptoms. However, the biophysical effects of RT are not specific to tumor cells and may produce toxicity due to exposure of surrounding organs and tissues. In this article, the authors review the clinical context, pathophysiology, risk factors, presentation, and management of RT side effects in each human organ system. Ionizing radiation works by producing DNA damage leading to tumor death, but effects on normal tissue may result in acute and/or late toxicity. The manifestation of toxicity depends on both cellular characteristics and affected organs' anatomy and physiology. There is usually a direct relationship between the radiation dose and volume to normal tissues and the risk of toxicity, which has led to guidelines and recommended dose limits for most tissues. Side effects are multifactorial, with contributions from baseline patient characteristics and other oncologic treatments. Technological advances in recent decades have decreased RT toxicity by dramatically improving the ability to deliver RT that maximizes tumor dose and minimizes organ dose. Thus the study of RT-associated toxicity is a complex, core component of radiation oncology training that continues to evolve alongside advances in cancer management. Because RT is used in up to one-half of all patients with cancer, an understanding of its acute and late effects in different organ systems is clinically pertinent to both oncologists and nononcologists., (© 2021 The Authors. CA: A Cancer Journal for Clinicians published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: As a result of tumor location and treatment that is aggressive, head and neck cancer (HNC) survivors experience an array of symptoms impacting the ability and desire to eat termed nutrition impact symptoms (NISs). Despite increasing cancer survival time, the majority of research studies examining the impact of NISs have been based on clinical samples of HNC patients during the acute phase of treatment. NISs are often chronic and persist beyond the completion of treatment or may develop as late side effects. Therefore, our research team examined chronic NIS complications on HNC survivors' functional status, quality of life, and diet quality., Methods: This was a cross-sectional study of 42 HNC survivors who were at least 6 months post-radiation. Self-reported data on demographics, NISs, quality of life, and usual diet over the past year were obtained. Objective measures of functional status included the short physical performance battery and InBody© 270 body composition testing. NISs were coded so a lower score indicated lower symptom burden, (range 4-17) and dichotomized as ≤10 vs. >10, the median in the dataset. Wilcoxon rank sum tests were performed between the dichotomized NIS summary score and continuous quality of life and functional status outcomes. Diet quality for HNC survivors was calculated using the Healthy Eating Index 2015 (HEI-2015). Wilcoxon rank sum tests examined the difference between the HNC HEI-2015 as compared to the National Health and Nutrition Examination Survey (NHANES) data calculated using the population ratio method., Results: A lower NIS score was statistically associated with higher posttreatment lean muscle mass ( p = 0.002). A lower NIS score was associated with higher functional ( p = 0.0006), physical ( p = 0.0007), emotional ( p = 0.007), and total ( p < 0.0001) quality of life. Compared to NHANES controls, HNC survivors reported a significantly lower HEI-2015 diet quality score ( p = 0.0001)., Conclusions: Lower NIS burden was associated with higher lean muscle mass and functional, physical, emotional, and total quality of life in post-radiation HNC survivors. HNC survivors reported a significantly lower total HEI-2015 as compared to healthy NHANES controls, providing support for the hypothesis that chronic NIS burden impacts the desire and ability to eat. The effects of this pilot study were strong enough to be detected by straight forward statistical approaches and warrant a larger longitudinal study. For survivors most impacted by NIS burden, multidisciplinary post-radiation exercise and nutrition-based interventions to manage NISs and improve functional status, quality of life, and diet quality in this survivor population are needed.

Background: Radiation therapy causes histopathologic changes in tissues, including fibrosis, loss of tissue planes, and vascular damage, which can lead to chronic wound formation. Patients with nonhealing, irradiated wounds and comorbidities that affect microvasculature suffer a "double hit", which leads to delayed wound healing. Local wound care and grafts are commonly insufficient. In this study, we evaluated limb salvage outcomes and long-term complications after free tissue transfer (FTT) in patients with chronic, irradiated leg wounds., Methods: We retrospectively reviewed patients with irradiated lower extremity wounds who underwent FTT from 2012 to 2017. Primary outcomes included limb salvage, ambulation, and overall flap success. Reconstruction involved complete excision of irradiated tissue and coverage with well-vascularized tissue., Results: Seven free flaps in six patients were identified. Average age was 68.4 years and average BMI was 27.8 kg/m 2 . Comorbid conditions included hypertension (57.1%), peripheral vascular disease (57.1%), underlying hypercoagulability (42.9%), diabetes (14.3%), and tobacco use (14.3%). Wounds were present for an average of 25.5 months prior to FTT. Donor sites included anterolateral thigh (71.4%), vastus lateralis (14.3%), and latissimus dorsi (14.3%). Overall flap success rate was 100% with one patient requiring reoperation for dehiscence. Limb salvage rate was 85.7% with one patient undergoing elective amputation due to pain. All patients could ambulate (one used a prosthesis) at a mean follow-up time of 1.4 years., Conclusions: Radiation therapy in a comorbid population often leads to the formation of chronic nonhealing wounds. We advocate for earlier consideration of FTT to provide healthy vascularized tissues, thereby avoiding prolonged wound care and patient burden. Successful limb salvage outcomes can be achieved., Competing Interests: Declaration of Competing Interest None declared, (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Myokymic discharges are classically associated with nerve injury from prior radiation but may occur in other neuromuscular disorders. Using quantitative analysis we aimed to identify the spectrum of conditions in which myokymic discharges are present and determine if there are electrophysiological features that distinguish postradiation from nonradiation causes of myokymia., Methods: We reviewed the clinical history of all patients examined in our electromyography labs with myokymic discharges recorded from June 2017 to February 2020. Quantitative analysis of each myokymic discharge was performed using a custom MATLAB script, assessing features such as burst frequency, spikes per burst, and burst regularity., Results: Eighty-eight distinct myokymic discharges (70 patients) were analyzed: 51 postradiation recordings from 35 patients and 37 recordings from 35 nonradiation patients. The diagnostic spectrum of nonradiation cases was diverse, with common causes being median neuropathy (n = 8), cervical (n = 7), and lumbar (n = 5) radiculopathy, and motor neuron disease (n = 5). On quantitative analysis, postradiation myokymia had an increased burst-to-silence ratio (median, 0.29; nonradiation, 0.08) and greater peak number (median, 15; nonradiation, 7). Except for one patient with hereditary peripheral nerve hyperexcitability, all patients who had two or more muscles demonstrating myokymic discharges belonged to postradiation group., Conclusions: Myokymic discharges can be seen in diverse neuromuscular conditions; most common in our cohort was chronic median neuropathy. Postradiation myokymia appears to have distinguishing morphological features when quantitatively analyzed compared with nonradiation cases., (© 2021 Wiley Periodicals LLC.)

Lung cancer is a leading cause of death worldwide. Radiation therapy (RT) is one method to treat this disease. A common side effect of RT for lung cancer is radiation-induced lung damage (RILD) which leads to loss of lung function. RILD often compounds pre-existing smoking-related regional lung function impairment. It is difficult to predict patient outcomes due to large variability in individual response to RT. In this study, the capability of image-based modelling of regional ventilation in lung cancer patients to predict lung function post-RT was investigated. Twenty-five patient-based models were created using CT images to define the airway geometry, size and location of tumour, and distribution of emphysema. Simulated ventilation within the 20 Gy isodose volume showed a statistically significant negative correlation with the change in forced expiratory volume in 1 s 12-months post-RT (p = 0.001, R = - 0.61). Patients with higher simulated ventilation within the 20 Gy isodose volume had a greater loss in lung function post-RT and vice versa. This relationship was only evident with the combined impact of tumour and emphysema, with the location of the emphysema relative to the dose-volume being important. Our results suggest that model-based ventilation measures can be used in the prediction of patient lung function post-RT.

Laryngeal carcinomas are the most common upper respiratory tract cancers and most commonly involve the glottic region. The aim of this study is to evaluate the voice quality after radiotherapy (RT) and microsurgical cordectomy (MC) treatments using Voice Handicap Index (VHI) and Grade, Roughness, Breathiness, Astenicity, and Strain (GRBAS) perceptual evaluation scale in patients with early-stage glottic carcinoma. A total of 37 patients with early-stage glottic carcinomas, 19 patients had RT and 18 patients with MC, were included in our study. The patients were evaluated in terms of their sound quality by using VHI-10 and GRBAS perceptual assessment scale 3 months after the treatment was completed. Although the findings were better in favor of RT according to GRBAS perceptual assessment scale of patients who received RT (n = 19) and MC (n = 18), no statistically significant difference was found between the 2 groups ( P = .613). Patients in both groups were evaluated with VHI-10, emotional ( P = .036) and physiological ( P = .038) scores were significantly higher in MC group and no significant difference was found in functional scores ( P = .192). However, there was no statistically significant difference between the 2 groups in terms of voice quality ( P = .185). In early-stage (Tis, T1a, T1b) glottic carcinoma, there was no significant difference between RT and MC in terms of voice quality. Therefore, the choice of treatment modality in patients with early-stage glottic carcinoma should be taken into account in terms of the patient's occupation, comorbid diseases, cost of treatment, hospital stay, and, most importantly, patient preference.

Despite the monumental advances in the diagnoses and therapeutics of malignancy, several cancer patients have presented with pericardial involvement, including acute pericarditis, constrictive pericarditis, and pericardial effusion. Multiple factors can contribute to acute pericarditis, including direct metastasis to the heart, pericardial hemorrhage, infections due to immunosuppression, and cancer therapies that include chemotherapy, immunotherapy, and radiation. Pericardial effusion, either due to cancer invasion or cancer treatment, is one of the most common incidental findings in cancer patients, which significantly worsens morbidity and mortality. If left untreated, pericardial effusion is known to cause complications such as pericardial tamponade. Constrictive pericarditis can be due to radiation exposure, chemotherapy, or is a sequela of a previous episode of acute pericarditis. In conclusion, early detection, prompt treatment, and understanding of pericardial diseases are necessary to help improve the quality of life of cancer patients, and we aim to summarize the knowledge of pericardial involvement in patients with cancer., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Thyroid cancer is one of the most common carcinomas diagnosed in adolescents and young adults, with a rapidly rising incidence for the past three decades. Surgery is the standard treatment for patients with differentiated thyroid carcinoma (DTC), and when indicated, followed by radioactive iodine (RAI) treatment. The aim of this study was to evaluate the possible effects of RAI therapy on ovarian function and fertility in women. Methods: The PubMed, Embase, and Web of Science databases were systematically searched up to January 2020. In addition, a meta-analyses were performed for anti-Mullerian hormone (AMH) levels after RAI, comparison of AMH levels prior and 1 year after RAI, and pregnancy rates in patient with thyroid cancer receiving RAI compared with patients with thyroid cancer who did not receive RAI. Results: A total of 36 studies were eligible for full-text screening and 22 studies were included. The majority of the studies had a retrospective design. Menstrual irregularities were present in the first year after RAI in 12% and up to 31% of the patients. Approximately 8-16% of the patients experienced amenorrhea in the first year after RAI. Women who received RAI treatment (median dose 3700 MBq [range 1110-40,700 MBq]); had menopause at a slightly younger age compared with women who did not receive RAI treatment, 49.5 and 51 years, respectively ( p  < 0.001). Pooled AMH of the seven studies reporting AMH concentrations after RAI was 1.79 ng/mL. Of these, four studies reported AMH concentrations prior and 1 year after RAI. The mean difference was 1.50 ng/mL, which was significant. Finally, meta-analysis showed that patients undergoing RAI were not at a decreased risk of becoming pregnant. Conclusions: Most of the studies indicate that RAI therapy for DTC is not associated with a long-term decrease in pregnancy rates although meta-analyses show a significant decrease in AMH levels after RAI therapy. Prospective studies are needed to confirm these results. We recommend counseling patients about the possible effects of 131 I and incorporate today's knowledge in multidisciplinary counseling.

The purpose of this study was to use a murine model to determine if melatonin can protect the inner ear from radiation-induced damage. A total of 81 4-week-old Balb/c mice were randomly divided into five groups: control group; 50 mg/kg melatonin group; 5 mg/kg melatonin+radiotherapy group; 50 mg/kg melatonin+radiotherapy group; radiotherapy group. The radiotherapy groups received 16 Gy irradiation and melatonin was administered by intraperitoneal injection 30 min before radiotherapy. On days 3 and 7 after irradiation the function of outer hair cells was determined by auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) testing, pathological changes of inner ear cells were observed by light microscopy, and the expression of prestin mRNA was determined. ABR thresholds were increased and wave I latencies were extended after radiotherapy; however, the increases were lower in the groups that received melatonin (P < 0.05). DPOAEs showed radiotherapy-induced hearing loss at 8-12 kHz, and hearing loss was greater on day 7 than day 3. However, hearing loss was less in the melatonin groups (P < 0.05). Histopathological examination showed irradiation resulted in breaks and distortion of the cochlear basement membrane, disruption of the stria vascularis, and swelling of outer hair cells. Melatonin reduced these changes. Radiotherapy upregulated prestin mRNA expression. Radiotherapy-induced upregulation of prestin was decreased in the melatonin groups (P < 0.05), and the decrease was greater in the 50 mg/kg melatonin group (P < 0.05). Melatonin protects against radiation-induced cochlear damage by reducing damage to outer hair cells., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Objective: Radiotherapy of head and neck cancer (HNCA) causes dysfunction through radiation-induced fibrosis (RIF). We hypothesize that the degree of cervical fibrosis is associated with swallowing dysfunction. This study evaluated the association between cervical fibrosis and swallowing dysfunction in patients after radiation therapy for HNCA., Study Design: Cross sectional study., Methodology: A convenience sample of patients with dysphagia who were at least 1 year post radiation therapy for HNCA underwent simultaneous cervical ultrasound (US) and video-fluroscopic swallow study (VFSS). US determinants of fibrosis were measurements of sternocleidomastoid fascia (SCMF) thickness bilaterally at the level of the cricoid. Primary and secondary outcome variables on VFSS were pharyngeal constriction ratio, a validated measure of pharyngeal contractility, and penetration aspiration scale (PAS). A qualitative assessment of lateral neck rotation was performed as a functional measure of neck fibrosis., Results: Simultaneous cervical US and VFSS examinations were performed on 18 patients with a history of radiotherapy for HNCA and on eight controls. The mean (±SD) age of the entire cohort (N = 26) was 66 (±10) years. Individuals with a history of radiation had significantly thinner mean SCMF (0.26 [±0.04 mm]) compared to controls (0.48 [±0.06 mm]; P < .05). Individuals with thinner SCMF were more likely to have moderate to severe restriction in lateral neck rotation, a higher PCR, and a higher PAS (P < .05)., Conclusion: Thinner sternocleidomastoid fascia on ultrasound in patients having undergone radiotherapy for head and neck cancer was associated with reduced lateral neck movement, poorer pharyngeal constriction and greater penetration/aspiration scale. The data suggest that cervical fibrosis is associated with swallowing dysfunction in head and neck cancer survivors and support the notion that, "As the neck goes, so does the swallow.", Level of Evidence: 3. Laryngoscope, 131:548-552, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Glaucoma is a leading cause of blindness worldwide. In glaucoma, a progressive dysfunction and death of retinal ganglion cells occurs, eliminating transfer of visual information to the brain. Currently, the only available therapies target the lowering of intraocular pressure, but many patients continue to lose vision. Emerging pre-clinical and clinical evidence suggests that metabolic deficiencies and defects may play an important role in glaucoma pathophysiology. While pre-clinical studies in animal models have begun to mechanistically uncover these metabolic changes, some existing clinical evidence already points to potential benefits in maintaining metabolic fitness. Modifying diet and exercise can be implemented by patients as an adjunct to intraocular pressure lowering, which may be of therapeutic benefit to retinal ganglion cells in glaucoma.

Background: Taste changes are commonly reported by people with cancer undergoing radio- or chemotherapy. Taste changes may compromise dietary intake and nutritional status., Objective: To understand whether or not taste change is associated with cancer diagnosis or treatment modality in adults., Methods: A systematic literature search up to December 31, 2019, was conducted using PubMed, Embase, and PsycInfo (International Prospective Register of Systematic Reviews protocol no. CRD42019134005). Studies in adults with cancer objectively assessing the effect of a cancer diagnosis or chemotherapy and/or radiotherapy treatment on taste function compared with healthy controls or within participant changes were included. Additional outcomes were food liking, appetite, dietary intake, nutritional status, and body composition. Reference lists of relevant articles were searched to identify additional articles. Quality was assessed using the Academy of Nutrition and Dietetics quality criteria checklist., Results: A total of 24 articles were included, one of which consisted of two studies that reported the effects of radiotherapy and chemotherapy separately. From the total 25 studies reported in 24 published articles, 14 studies examined effects of radiotherapy, and remaining 11 studies examined chemotherapy. There is limited evidence of a cancer diagnosis per se contributing to taste dysfunction. Impaired taste function was reported in almost all radiotherapy studies, occurring as early as Week 3 of treatment and lasting for 3 to 24 months posttreatment. During chemotherapy, impairment of taste function was less consistently reported, occurring as early as the first few days of chemotherapy, and persisting up to 6 months posttreatment. Taxane-based chemotherapy was reported to affect taste function more than other treatments. Several studies reported reduced liking for food, appetite, and dietary intake. Only one study reported nutritional status of participants, finding no association between taste function and nutritional status. No studies examined associations between taste changes and body composition., Conclusions: This review highlights the importance of considering treatment modality in practice. Research is required to identify factors contributing to taste alteration and to inform evidence-based interventions., (Copyright © 2021 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Chemo-radiotherapy and systemic therapies have proven satisfactory outcomes as standard treatments for various thoracic malignancies; however, adverse pulmonary effects, like pneumonitis, can be life-threatening. Pneumonitis is caused by direct cytotoxic effect, oxidative stress, and immune-mediated injury. Radiotherapy Induced Lung Injury (RILI) encompasses two phases: an early phase known as Radiation Pneumonitis (RP), characterized by acute lung tissue inflammation as a result of exposure to radiation; and a late phase called Radiation Fibrosis (RF), a clinical syndrome that results from chronic pulmonary tissue damage. Currently, diagnoses are made by exclusion using clinical assessment and radiological findings. Pulmonary function tests have constituted a significant step in evaluating lung function status during radiotherapy and useful predictive tools to avoid complications or limit toxicity. Systemic corticosteroids are widely used to treat pneumonitis complications, but its use must be standardized, and consider in the prophylaxis setting given the fatal outcome of this adverse event. This review aims to discuss the clinicopathological features of pneumonitis and provide practical clinical recommendations for prevention, diagnosis, and management.

Purpose: To define the temporal relationship of vascular versus neuronal abnormalities in radiation retinopathy., Methods: Twenty-five patients with uveal melanoma treated with brachytherapy and sixteen controls were tested. Functional outcome measures included visual acuity and threshold perimetry (HVF 10-2), while structural outcomes included retinal thickness by OCT and vascular measures by OCT angiography and digital fundus photography. The degree of structural abnormality was determined by intereye asymmetry compared with normal subject asymmetry. Diagnostic sensitivity and specificity of each measure were determined using receiver operating characteristic curves. The relationships between the outcome measures were quantified by Spearman correlation. The effect of time from brachytherapy on visual function, retinal layer thickness, and capillary density was also determined., Results: Within the first 2 years of brachytherapy, outcome measures revealed visual field loss and microvascular abnormalities in 38% and 31% of subjects, respectively. After 2 years, they became more prevalent, increasing to 67% and 67%, respectively, as did retinal thinning (50%). Visual field loss, loss of capillary density, and inner retinal thickness were highly correlated with one another. Diagnostic sensitivity and specificity were highest for abnormalities in digital fundus photography, visual field loss within the central 10°, and decrease in vessel density., Conclusions: Using quantitative approaches, radiation microvasculopathy and visual field defects were detected earlier than loss of inner retinal structure after brachytherapy. Strong correlations eventually developed between vascular pathology, change in retinal thickness, neuronal dysfunction, and radiation dose. Radiation-induced ischemia seems to be a primary early manifestation of radiation retinopathy preceding visual loss.

Background: Patients meeting criteria for intervention of carotid stenosis with a history of prior cervical radiation or neck dissection are considered "high risk" for carotid endarterectomy. This is a well-established indication for carotid artery stenting (CAS). The long-term outcomes of CAS in this population are less frequently published in the literature but are poor. The purpose of this study was to review long-term results of CAS in veteran patients with a prior history of treatment for head and/or neck cancer., Methods: This is a retrospective review of a veteran patient population from 1998 to 2016. All patients at our institution with a prior history of treatment for head and/or neck cancer who underwent CAS were included in the analysis. During this time period, 44 patients met inclusion criteria and were treated with 57 carotid stenting interventions. The Kaplan-Meier analysis was used to determine survival and primary patency. The secondary aims were to analyze early outcomes and to identify predictive risk factors for mortality and reintervention., Results: The mean follow-up was 42.9 ± 36.6 months. The cumulative survival at 1, 5, and 10 years was 91%, 67%, and 48%, respectively. The primary patency at 1, 5, and 10 years was 95%, 86%, and 86%, respectively. The reintervention rate was 11% (n = 6) with an assisted primary patency rate of 100%. No neurologic events occurred within 30 days. There were 3 strokes in late follow-up and no stroke-related deaths. Eighteen patients (41%) died during the follow-up period, 15 of whom died during the first 5 years of follow-up. Ten (66%) of those patients died of recurrent or active index cancer. On univariate analysis, tumor, node, metastasis stage IV was significantly associated with death (P = 0.02). Multivariate models were not statistically significant for predicting mortality or reintervention CONCLUSIONS: On the basis of the results in this series, CAS can be performed in these patients with low long-term rates of neurologic events and need for reintervention. However, the survival of patients with head and neck cancer undergoing CAS in this cohort is poor, which is consistent with other published series of patients undergoing CAS for head/neck cancer with at least 5-year follow-up. In this specific patient population, a more critical analysis of the patient's overall prognosis, especially as related to cancer, should be undertaken before offering CAS., (Copyright © 2020 Elsevier Inc. All rights reserved.)

As the multi-systemic components of COVID-19 emerge, parallel etiologies can be drawn between SARS-CoV-2 infection and radiation injuries. While some SARS-CoV-2-infected individuals present as asymptomatic, others exhibit mild symptoms that may include fever, cough, chills, and unusual symptoms like loss of taste and smell and reddening in the extremities (e.g., "COVID toes," suggestive of microvessel damage). Still others alarm healthcare providers with extreme and rapid onset of high-risk indicators of mortality that include acute respiratory distress syndrome (ARDS), multi-organ hypercoagulation, hypoxia and cardiovascular damage. Researchers are quickly refocusing their science to address this enigmatic virus that seems to unveil itself in new ways without discrimination. As investigators begin to identify early markers of disease, identification of common threads with other pathologies may provide some clues. Interestingly, years of research in the field of radiation biology documents the complex multiorgan nature of another disease state that occurs after exposure to high doses of radiation: the acute radiation syndrome (ARS). Inflammation is a key common player in COVID-19 and ARS, and drives the multi-system damage that dramatically alters biological homeostasis. Both conditions initiate a cytokine storm, with similar pro-inflammatory molecules increased and other anti-inflammatory molecules decreased. These changes manifest in a variety of ways, with a demonstrably higher health impact in patients having underlying medical conditions. The potentially dramatic human impact of ARS has guided the science that has identified many biomarkers of radiation exposure, established medical management strategies for ARS, and led to the development of medical countermeasures for use in the event of a radiation public health emergency. These efforts can now be leveraged to help elucidate mechanisms of action of COVID-19 injuries. Furthermore, this intersection between COVID-19 and ARS may point to approaches that could accelerate the discovery of treatments for both., (©2021 by Radiation Research Society. All rights of reproduction in any form reserved.)

Background: Computed tomography (CT) is the gold standard of body composition analysis at the tissue-organ level. The present study aimed to determine the impact of CT-defined sarcopenia and myosteatosis on outcomes, including overall survival, unplanned hospital admissions and related costs, in patients who had completed treatment of curative intent for head and neck cancer (HNC)., Methods: Retrospective observational study of patients undergoing radiotherapy of curative intent ± other treatment modalities for HNC. Tissue density data derived at the third lumbar vertebra (L3) were evaluated with sarcopenia defined per sex-specific published threshold values for skeletal muscle index, stratified by body mass index and mean skeletal muscle attenuation in HU (Hounsfield units)., Results: Pre- or post-treatment images were available for 79/98 patients (80.6%) and 61/98 patients (62.2%), respectively. Sarcopenia was present in 42/79 patients pre-treatment and 36/61 patients post-treatment, whereas myosteatosis was present in 63/79 patients pre-treatment and 48/61 patients post-treatment. In patients with pre- and post-treatment images (n = 60), the median (range) percentage weight change was -8.5% (-29.9 to +11.7). On multivariable analysis, a post-treatment sarcopenia hazard ratio of 3.87 (95% confidence interval = 1.22-12.24, P = 0.021) and a pre-treatment myosteatosis hazard ratio of 8.86 (95% confidence interval = 1.12-69.88, P = 0.038) were independent predictors of reduced overall survival. There was no difference in radiotherapy or chemotherapy treatment completion based on pre-treatment sarcopenia status. The mean (SD) difference unplanned hospital admission cost was $15 846 ($17 707) for patients without sarcopenia versus $47 945 ($82 688) for patients with sarcopenia at any time point (P = 0.077)., Conclusions: As CT-defined sarcopenia and myosteatosis hold clinically meaningful prognostic value, muscle status evaluation is recommended in routine clinical practice., (© 2020 The British Dietetic Association Ltd.)

Introduction: Stereotactic Body Radiotherapy (SBRT) in liver tumors allows ablative radiation doses in tumors preserving the liver tissue. However, liver is a parallel organ allowing high doses in a small region to preserve its function. If this is not possible, radio-induced liver toxicity is produced. Radio-induced liver toxicity or radio-induced liver disease (RILD) is the most serious toxicity in liver radiotherapy., Areas Covered: In this review, we analyzed published literature on PubMed and MEDLINE. We included papers in English language with information about RILD characteristics, diagnostic, risk factors, pathophysiology, and treatment. All citations were evaluated for relevant content and validation., Expert Opinion: The study of RILD is fundamental before the implementation of liver SBRT. Radio-induced liver toxicity is a complication that can be fatal for patients. This is a diagnosis of exclusion and it is essential that experts in the treatment of hepatic SBRT know about it and anticipate its development. The study and development of molecular or imaging biomarkers could be key in their diagnosis and prevention.

Purpose: Since the exact development of posterior subcapsular cataracts (PSCs) is poorly understood, we review various risk factors and propose a two-stage etiology for PSCs., Methods: The biological mechanisms associated with age-related cataracts (primarily nuclear cataracts, cortical cataracts and PSCs) were reviewed in relation to selected risk factors that induce PSCs (including atopy, diabetes, hypoparathyroidism, myopia, retinitis, solar radiation, steroid use, uveitis, vitrectomy and ionizing radiation). We particularly focused on ionizing radiation, as this is known to be a risk factor specific to PSCs. Based on an analysis of the reviewed material, we propose a detailed explanation of the etiology of PSCs., Conclusions: Lens epithelial cells (LECs) and lens fiber cells are normally hypoxic and therefore very sensitive to changes in oxidative stress, as quantified by the radiation oxygen effect. We hypothesize that the development of PSC opacities is a two-stage process. Stage I, early in life, is driven by risk factors that promote oxidative stress and ion-pump disruption, harming lens fibers and causing aberrant LECs to proliferate and ectopically migrate as Wedl cells (perhaps by processes associated with an epithelial to mesenchymal transition) to the posterior pole region. After a latent period, in Stage II, the development of PSCs advances mainly due to chronic inflammation and other premature aging-related mechanisms that promote mature vacuolar or plaque PSC. This two-stage hypothesis of PSC etiology accounts for risk factors, such as aging, diabetes and ionizing radiation, which directly affects LECs and the lens. In addition, these risk factors can damage other ocular regions, such as the retina and vitreous, that also indirectly contribute to the development of PSCs. It is possible that the incidence of PSCs may be reduced by reversing the effects of Stage I through various means, including ocular antioxidants.

Recent studies suggested that radiation exposure causes local and systemic inflammatory responses and induces cell and tissue damage. We have reported that IL-18 plays an important role in radiation-induced injury. Here, we demonstrate that IL-18 binding protein (IL-18BP), a natural antagonist of IL-18, was significantly increased (1.7-63 fold) in mouse serum on day 1 after 0.5-10 Gy TBI. However, this high level of IL-18BP was not sufficient to neutralize the active IL-18 in irradiated mice, resulting in a radiation dose-dependent free IL-18 increase in these mice's serum which led to pathological alterations to the irradiated cells and tissues and finally caused animal death. Administration of recombinant human (rh) IL-18BP (1.5 mg/kg) with single (24, 48 or 72 h post-TBI) or double doses (48 h and 5 days post-TBI) subcutaneous (SC) injection increased 30-day survival of CD2F1 mice after 9 Gy TBI 12.5-25% compared with the vehicle control treated group, respectively. Furthermore, the mitigative effects of rhIL-18BP included balancing the ratio of IL-18/IL-18BP and decreasing the free IL-18 levels in irradiated mouse serum and significantly increasing blood cell counts, BM hematopoietic cellularity and stem and progenitor cell clonogenicity in mouse BM. Furthermore, IL-18BP treatment inhibited the IL-18 downstream target interferon (IFN)-γ expression in mouse BM, decreased reactive oxygen species (ROS) level in the irradiated mouse heart tissues, attenuated the stress responsive factor GDF-15 (growth differentiation factor-15) and increased the intestine protector citrulline level in total body irradiated mouse serum, implicating that IL-18BP may protect multiple organs from radiation-induced inflammation and oxidative stress. Our data suggest that IL-18 plays a key role in radiation-induced cell and tissue damage and dysfunction; and for the first time demonstrated that IL-18BP counters IL-18 activation and therefore may mitigate/treat radiation-induced multiple organ injuries and increase animal survival with a wider therapeutic window from 24 h and beyond after lethal doses of radiation exposure.

Vasculature is necessary to the healthy function of most tissues. In radiation therapy, injury of the vasculature can have both beneficial and detrimental effects, such as tumor starvation, cardiac fibrosis, and white-matter necrosis. These effects are caused by changes in blood flow due to the vascular injury. Previously, research has focused on simulating the radiation injury of vasculature in small volumes of tissue, ignoring the systemic effects of local damage on blood flow. Little is known about the computational feasibility of simulating the radiation injury to whole-organ vascular networks. The goal of this study was to test the computational feasibility of simulating the dose deposition to a whole-organ vascular network and the resulting change in blood flow. To do this, we developed an amorphous track-structure model to transport radiation and combined this with existing methods to model the vasculature and blood flow rates. We assessed the algorithm's computational scalability, execution time, and memory usage. The data demonstrated it is computationally feasible to calculate the radiation dose and resulting changes in blood flow from 2 million protons to a network comprising 8.5 billion blood vessels (approximately the number in the human brain) in 87 hours using a 128-node cluster. Furthermore, the algorithm demonstrated both strong and weak scalability, meaning that additional computational resources can reduce the execution time further. These results demonstrate, for the first time, that it is computationally feasible to calculate radiation dose deposition in whole-organ vascular networks. These findings provide key insights into the computational aspects of modeling whole-organ radiation damage. Modeling the effects radiation has on vasculature could prove useful in the study of radiation effects on tissues, organs, and organisms.

Background/aim: Hypothalamic-pituitary (HT-P) dysfunction is one of the most common endocrine late effects following cranial radiotherapy. However, there are currently no specific data describing this complication in adult-onset cancer patients after whole brain radiotherapy (WBRT). The present cohort study aims to establish the prevalence of HT-P axis dysfunction in this group of patients., Patients and Methods: Twenty-six cancer patients previously treated with WBRT (median follow-up=20.5 months) received standardized endocrine check-up focusing on HT-P function., Results: In 50% of the patients, impaired hypothalamic-pituitary function was detected during follow-up. While functional loss of a single hormonal axis was evident in 34.6% of patients, 7.7% showed an impairment of multiple endocrine axes, and one patient developed adrenocorticotropic hormone deficiency. Hypothalamic-pituitary dysfunction did not directly correlate with the applied WBRT total doses., Conclusion: In our cohort, hypothalamic-pituitary dysfunction appeared to be common after WBRT and was diagnosed as early as 6 months following radiation. This finding highlights the need for routine endocrine follow-up even in patients with limited life expectancy., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Reproducible measurement of left ventricular (LV) systolic function by echocardiography is important to detect cancer therapy-related cardiac dysfunction (CTRCD). We hypothesized that limiting the number of imaging operators and use of a single vendor would improve reproducibility of these measures. A standard operating procedure (SOP) whereby LV measurements were standardized and a cardio-oncology imaging team (5 sonographers, 6 cardiologists) was established. All pediatric oncology patient echocardiograms were acquired on a single vendor platform. In total, 100 consecutive pre-SOP and 100 post-SOP studies were reviewed. LV end-diastolic dimension (LVEDD), posterior wall thickness (PW), shortening fraction (SF), and ejection fraction by Simpson's biplane (EF) were re-measured by 2 blinded readers, and compared to what was originally reported. Image quality was scored by number of LV segments imaged (grades 1-4). Inter-observer reproducibility pre/post-SOP was assessed with intra-class coefficient (α). Reducing the number of imaging operators improved image quality (Grade ≥ 3: 13% vs. 46%, p < 0.001). Reproducibility of PW and LVEDD marginally improved (PW: 0.78 to 0.82; LVEDD: 0.96 to 0.97), and SF improved significantly (α = 0.65 vs. 0.79, p < 0.001). Pre-SOP reproducibility of LV EF was poor (α = 0.65), but improved significantly post-SOP (α = 0.83, p < 0.001). Reproducibility of LV EF improved with higher image quality score. Limiting imaging operators and vendor platform for pediatric oncology echocardiograms improves image quality and reproducibility of LV EF. Establishing an SOP and a cardio-oncology echocardiography team may improve precision of measurements used to detect CTRCD.

Background: Pediatric cancer survivors are at increased risk of cardiac dysfunction and heart failure. Reduced peak oxygen consumption (peak VO 2 ) is associated with impaired cardiac reserve (defined as the increase in cardiac function from rest to peak exercise) and heart failure risk, but it is unclear whether this relationship exists in pediatric cancer survivors. This study sought to investigate the presence of reduced peak VO 2 in pediatric cancer survivors with increased risk of heart failure, and to assess its relationship with resting cardiac function and cardiac haemodynamics and systolic function during exercise., Methods: Twenty pediatric cancer survivors (8-24 years; 10 male) treated with anthracycline chemotherapy ± radiation underwent cardiopulmonary exercise testing to quantify peak VO 2 , with a value < 85% of predicted defined as impaired peak VO 2 . Resting cardiac function was assessed using 2- and 3-dimensional echocardiography, with cardiac reserve quantified from resting and peak exercise heart rate, stroke volume index (SVI) and cardiac index (CI) using exercise cardiovascular magnetic resonance (CMR)., Results: Twelve of 20 survivors (60%) had reduced peak VO 2 (70 ± 16% vs. 97 ± 14% of age and gender predicted). There were no differences in echocardiographic or CMR measurements of resting cardiac function between survivors with normal or impaired peak VO 2 . However, those with reduced peak VO 2 had diminished cardiac reserve, with a lesser increase in CI and SVI during exercise (Interaction P < 0.01 for both), whilst the heart rate response was similar (P = 0.71)., Conclusions: Whilst exercise intolerance is common among pediatric cancer survivors, it is poorly explained by resting measures of cardiac function. In contrast, impaired exercise capacity is associated with impaired haemodynamics and systolic functional reserve measured during exercise. Consequently, measures of cardiopulmonary fitness and cardiac reserve may aid in early identification of survivors with heightened risk of long-term heart failure.

Purpose: Exposure to ionizing radiation following environmental contamination (e.g., the Chernobyl and Fukushima nuclear accidents), radiotherapy and diagnostics, occupational roles and space travel has been identified as a possible risk-factor for cognitive dysfunction. The deleterious effects of high doses (≥1.0 Gy) on cognitive functioning are fairly well-understood, while the consequences of low (≤0.1 Gy) and moderate doses (0.1-1.0 Gy) have been receiving more research interest over the past decade. In addition to any impact of actual exposure on cognitive functioning, the persistent psychological stress arising from perceived exposure, particularly following nuclear accidents, may itself impact cognitive functioning. In this review we offer a novel interdisciplinary stance on the cognitive impact of radiation exposure, considering psychological and epidemiological observations of different exposure scenarios such as atomic bombings, nuclear accidents, occupational and medical exposures while accounting for differences in dose, rate of exposure and exposure type. The purpose is to address the question that perceived radiation exposure - even where the actual absorbed dose is 0.0 Gy above background dose - can result in psychological stress, which could in turn lead to cognitive dysfunction. In addition, we highlight the interplay between the mechanisms of perceived exposure (i.e., stress) and actual exposure (i.e., radiation-induced cellular damage), in the generation of radiation-induced cognitive dysfunction. In all, we offer a comprehensive and objective review addressing the potential for cognitive defects in the context of low- and moderate-dose IR exposures., Conclusions: Overall the evidence shows prenatal exposure to low and moderate doses to be detrimental to brain development and subsequent cognitive functioning, however the evidence for adolescent and adult low- and moderate-dose exposure remains uncertain. The persistent psychological stress following accidental exposure to low-doses in adulthood may pose a greater threat to our cognitive functioning. Indeed, the psychological implications for instructed cohorts (e.g., astronauts and radiotherapy patients) is less clear and warrants further investigation. Nonetheless, the psychosocial consequences of low- and moderate-dose exposure must be carefully considered when evaluating radiation effects on cognitive functioning, and to avoid unnecessary harm when planning public health response strategies.

Background: Changes in radiation therapy practice and cancer incidence bring into question prior evidence suggesting that radiation therapy predominantly injures the brachial plexus upper trunk, while tumor invasion typically injures the lower trunk., Methods: We reviewed electrodiagnostic brachial plexopathy reports in cancer survivors for predominant trunk involvement, injury mechanism (tumor invasion vs radiation), and primary cancer location., Results: Fifty-six cases of cancer-associated brachial plexopathy were identified. There was no relationship between injury mechanism and brachial plexus injury level. However, primary cancer location superior/inferior to the clavicle increased the odds of predominantly upper/lower trunk involvement by a factor of 60.0 (95% confidence interval: 7.9, 1401, respectively)., Conclusions: Cancers superior/inferior to the clavicle increase the likelihood of predominantly upper/lower trunk plexopathy, respectively, regardless plexus injury mechanism. These findings contrast with older work, possibly due to more precise radiation therapy techniques and increased incidence of radiosensitive head and neck cancers., (© 2020 Wiley Periodicals LLC.)

Wound healing is affected by several factors. Preexisting diagnoses may significantly alter, delay, or inhibit normal wound healing. This is most commonly seen with chronic disorders, such as diabetes and renal failure, but also occurs secondary to aging and substance abuse. Less commonly, genetic or inflammatory disorders are the cause of delayed wound healing. In some cases, it is not the illness, but the treatment that can inhibit wound healing. This is seen in patients getting chemotherapy, radiation, steroids, methotrexate, and a host of other medications. Understanding these processes may help treat or avoid wound healing problems., Competing Interests: Disclosure The authors have nothing to disclose., (Published by Elsevier Inc.)

Purpose: To assess efficacy of intravitreal ranibizumab injections and targeted panretinal photocoagulation (TRP) for radiation retinopathy-related macular edema., Design: Phase IIb, prospective, randomized clinical trial., Methods: Setting: Multicenter., Subjects: Forty eyes in 40 treatment-naïve patients with radiation-induced macular edema and a resulting decrease in visual acuity ranging between 20/25 and 20/400 (Snellen equivalent)., Intervention: Patients either received intravitreal 0.5 mg ranibizumab monthly, monthly ranibizumab with TRP, or 3 monthly ranibizumab (loading doses) followed by as-needed (PRN) injections and TRP. After week 52, all subjects entered a treat-and-extend protocol for ranibizumab. MainOutcomeMeasures: Mean Early Treatment Diabetic Maculopathy Study (ETDRS) BCVA change from baseline., Results: Mean patient age was 57 years (range, 22-80 years), ETDRS BCVA was 56.7 letters (20/74 Snellen equivalent), and central macular thickness (CMT) was 423 μm (range, 183-826 μm). Thirty-seven patients completed the month 12 visit (92.5%), at which time the change in mean BCVA was +4.0 letters, -1.9 letters, and +0.9 letters in the monthly, monthly plus laser, and PRN plus laser cohorts, respectively. There was a significant difference in mean BCVA at 1 year among all 3 cohorts (P < .001), as well as between cohorts in pairwise comparisons, with the most significant gains in the monthly group. A total of 82.5% of the patients retained visual acuity of 20/200 or better, and 20.0% improved 10 or more ETDRS letters., Conclusions: Ranibizumab may improve vision and anatomy in patients with radiation retinopathy-related macular edema and prevent vision loss through 48 weeks of therapy. Monthly injections were more effective than as-needed approach, and the addition of TRP yielded no therapeutic benefits., (Copyright © 2020 Elsevier Inc. All rights reserved.)