Update on lacrimal apparatus dysfunction associated with differentiated thyroid cancer after I-131 therapy.

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.

Oxidative and Nitrous Stress Underlies Vascular Malfunction Induced by Ionizing Radiation and Diabetes.

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, BKCa, 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.

Application of two-dimensional speckle-tracking echocardiography in radiotherapy-related cardiac systolic dysfunction and analysis of its risk factors: a prospective cohort study.

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.

Effects of Radiation on Olfactory Function in Head and Neck Malignancy.

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 (T0), at 2 weeks of RT(T1), end of RT (T2), 1 month follow-up (T3), and 3-month follow-up (T4). The near maximum dose to the nasal cavity (D2%) and mean dose to the nasal cavity (Dmean) 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.

Electromyography findings in radiation-induced unilateral tongue immobility.

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.

Effects of low dose ionizing radiation on the brain- a functional, cellular, and molecular perspective.

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.

CLINICAL-METABOLIC AND HORMONAL RELATIONSHIPS BETWEEN PARATHYROID DISEASE AND OTHER NON-CANCEROUS ENDOCRINE DISORDERS IN THE CHORNOBYL NPP ACCIDENT SURVIVORS. / KLINIKO-METABOLIChNI TA GORMONAL'NI VZAIeMOZV'IaZKY MIZh PATOLOGIIeIu PRYShchYTOPODIBNYKh ZALOZ TA INShYMY NEZLOIaKISNYMY ENDOKRYNNYMY ZAKhVORIuVANNIaMY U POSTRAZhDALYKh VNASLIDOK AVARIÏ NA ChAES.

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 «iodine¼ 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 «iodine¼ 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.

SKIN AND SUBCUTANEOUS ADIPOSE TISSUE DAMAGE AFTER RADIATION THERAPY IN BREAST CANCER PATIENTS. / POShKODZhENNIa ShKIRY I PIDShKIRNOÏ ZhYROVOÏ KLITKOVYNY PISLIa PROMENEVOÏ TERAPIÏ U KhVORYKh NA RAK MOLOChNOÏ ZALOZY.

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.

LONG/TERM GENETIC AND EPIGENETIC DISORDERS IN PERSONS EXPOSED TO IONIZING RADIATION AND THEIR DESCENDANTS (review). / VIDDALENI GENETYChNI TA EPIGENETYChNI PORUShENNIa U OPROMINENYKh OSIB TA ÏKhNIKh NAShchADKIV (ogliad).

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.

THE BRONCHOPULMONARY SYSTEM DAMAGE UNDER THE INFLUENCE OF IONIZING RADIATION EXPOSURE AND RADIONUCLIDES INHALATION IN THE CONDITIONS OF THE CHORNOBYL CATASTROPHE (SUMMARIZING OF 35 YEARS RESEARCH EXPERIENCE). / URAZhENNIa BRONKhOLEGENEVOÏ SYSTEMY VNASLIDOK VPLYVU IONIZUIuChOGO OPROMINENNIa TA INGALIaTsIINOGO NADKhODZhENNIa RADIONUKLIDIV V UMOVAKh ChORNOBYL'S'KOÏ KATASTROFY (UZAGAL'NENNIa DOSVIDU 35 ROKIV DOSLIDZhEN').

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 «targets¼-tissues, of realization of stochastic and nonstochastic effects.

BRAIN AND EYE AS POTENTIAL TARGETS FOR IONIZING RADIATION IMPACT: PART II - RADIATION CEREBRO/OPHTALMIC EFFECTS IN CHILDREN, PERSONS EXPOSED IN UTERO, ASTRONAUTS AND INTERVENTIONAL RADIOLOGISTS. / GOLOVNYI MOZOK TA ORGAN ZORU IaK POTENTsIINI MIShENI DLIa VPLYVU IONIZUIuChOGO VYPROMINIuVANNIa: ChASTYNA II ­ RADIATsIINI TsEREBROOFTAL'MOLOGIChNI EFEKTY U DITEI, OSIB, EKSPONOVANYKh VNUTRIShN'O/UTROBNO, ASTRONAVTIV TA INTERVENTsIINYKh RADIOLOGIV.

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 axis¼. 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.

ASSESSMENT OF QUALITATIVE CHANGES IN PERIPHERAL BLOOD CELLS IN CHILDREN - RESIDENTS OF RADIOLOGICALLY CONTAMINATED TERRITORIES IN THE LATE PERIOD AFTER THE ChNPP ACCIDENT. / OTsINKA IaKISNYKh ZMIN V ELEMENTAKh PERYFERYChNOÏ KROVI U DITEI ­ MEShKANTsIV RADIOAKTYVNO ZABRUDNENYKh TERYTORII U VIDDALENYI PERIOD PISLIa AVARIÏ NA ChAES.

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.

COMORBID INTERNAL DISEASES IN MILITARY SERVANTS WHO HAVE SENSED THE EXPOSURE OF EXTREME FACTORS OF MILITARY SERVICE. / KOMORBIDNI VNUTRIShNI ZAKhVORIuVANNIa U VIIS'KOVOSLUZhBOVTsIV, IaKI ZAZNALY VPLYVU EKSTREMAL'NYKh FAKTORIV VIIS'KOVOÏ SLUZhBY.

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 Hospital¼ NMMCC «MMCH¼ 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.

CYTOGENETIC INDICATORS OF ACUTE RADIATION SICKNESS (THE CHORNOBYL EXPERIENCE). / TsYTOGENETYChNI POKAZNYKY GOSTROÏ PROMENEVOÏ KhVOROBY (ChORNOBYL'S'KYI DOSVID).

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 («liquidators¼) 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.

SUBCLINICAL INFLAMMATION IN NON/ALCOHOLIC FATTY LIVER DISEASE AT THE REMOTE PERIOD AFTER THE CHORNOBYL ACCIDENT. / SUBKLINIChNE ZAPALENNIa PRY NEALKOGOL'NII ZhYROVII KhVOROBI PEChINKY U VIDDALENOMU PERIODI PISLIa ChORNOBYL'S'KOÏ AVARIÏ.

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.

Cardio-Oncology Preclinical Models: A Comprehensive Review.

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.

Randomized Phase III Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for Small-Cell Lung Cancer (PREMER): A GICOR-GOECP-SEOR Study.

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.

Chronic Nutrition Impact Symptoms Are Associated with Decreased Functional Status, Quality of Life, and Diet Quality in a Pilot Study of Long-Term Post-Radiation Head and Neck Cancer Survivors.

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.