To assess the prevalence of refractive errors (REs) in school children aged 6–18 years in urban and rural settings in Dalian, Northeast of China.This is a school-based cross-sectional survey using multi-stage randomization technique. Six- to eighteen-year-old school children from elementary schools, junior and senior high schools from a rural area and an urban area in Dalian were included in December 2018. All subjects underwent a comprehensive questionnaire and eye examination.P < 0.001; OR = 1.29, 95 % CI = 1.00–1.67, P = 0.049), respectively. The hyperopia was less common in urban students than in rural ones . However, there was no significant difference in prevalence of astigmatism between urban (46.07%) and rural (44.69%) participants . The differences on prevalence of REs were attributed to different social-demographic and physiologic factors.A total of 4,522 school children with 6–18 years of age were investigated. The age, gender-adjusted prevalence of myopia, and anisometropia were 82.71 and 7.27% among the urban students as compared to 71.76% and 5.41% among the rural ones (OR = 1.80, 95 % CI = 1.53 - 2.11, The students from urban settings are more likely to have myopia and anisometropia but less likely to have hyperopia than their rural counterparts. Although considerable attention had been paid to controlling REs, it is necessary to further consider the urban-rural differences in REs. The refractive errors (REs), especially myopia, have become the primary cause of vision impairment (VI) and preventable blindness in children. Myopia suggests a significant increase in prevalence globally in the past 50 years and become a significant public health problem across the globe, especially in East Asian countries like Singapore and China , 2. In SVarious factors, including genetic and environmental factors play a role in the etiology of myopia. Genetically, the prevalence of myopia in children is greater if their parents are myopic , 12. RapAt present, the prevalence and risk factors of REs in urban and rural school children in Northeast China are still unclear. Whether there are differences in the associated factors of REs in different regions needs further research. In order to understand the prevalence of REs and the risk factors disparity among school children (6–18 years old) between urban and rural settings, we performed this school-based survey in the urban and rural areas of Dalian, Northeast China.This school-based study was initially performed in December 2018. Multi-stage random cluster approach was conducted for sampling. In the first step, one district from each of the rural (Wafangdian County) and urban (Xigang District) regions of Dalian was randomly selected. In the second step, one primary school, one junior high school, and one senior high school were randomly selected from each of the two selected districts. In the third step, two classes of each grade were of randomly selected from each of the including schools. In the final step, all students of the selected classes with age of 6–18 years were sampled. The exclusion criteria were the followings: (1) Participants who reported eye conditions within the last month ; (2) Participants whose parents refused to sign the informed consents.The study was approved by the respective ethics committees of The Third People‘s Hospital of Dalian and the Health commission of Dalian. This study followed the Declaration of Helsinki. Written consent was obtained from the parents of all children and teenagers.In current study, all participants and their parents completed a detailed questionnaire form. The quality of the questionnaire was controlled by head teacher in each class. The questionnaires are conducted at home.The questionnaire included two parts (participants' information section and parents' information section). Basic socio-demographic data, such as age, gender, ethnic origin, habitation in urban or rural areas, degree of class and grade, and medical history was included in the first part of the questionnaire. Moreover, this questionnaire section additionally included questions on near-work activities such as the amount of time spent on studying or watching television, mobile phone and on computer activities per day. The first part of the questionnaire also includes questions about outdoor activities such as how long the children spent in outdoor activities per day. The first part of the questionnaire was filled in by the children and assisted by their parents. For very young children who could not read or understand the questionnaire very well , help was sought from their parents.In the second part, information of parents' education level, refractive error history  were obtained using questionnaire from participants‘ parents.After the interview, comprehensive ophthalmological examinations were conducted on the school premises by two trained optometrists. Refractive error measurements, uncorrected visual acuity as well as best corrected visual acuity (BCVA) were tested using non-cycloplegic auto-refractometry  by a senior experienced optometrist. Moreover, intraocular pressure (IOP) was measured by non-contact tonometry . Axial length was tested by IOL Master . The mean of three readings were taken.The definitions of refractive error vary across the selected prevalence studies, we choose the definition that is common in clinical use , 20. Thet-test for the continuous variables and the Pearson's χ2 test for the categorical variables. Logistic regression analysis was performed to determine risk factors using odds ratio (OR) estimates with 95% confidence intervals (CI). A multivariate regression analysis was performed with P-value < 0.05 being required for entering the model. All P-values were 2-sided and considered statistically significant when <0.05.The data were analyzed using a commercially available statistical program SAS 9.3  and SPSS 20.0 . Only the data for eye with high severity of refraction is presented. Participants included in the final analysis were divided into three age groups  which were consistent with the distribution of education level for including participants. The age- and gender-specific prevalence rates of REs and subtypes were assessed. The difference of the variables  with REs was assessed using the Student's P < 0.001), annual household income exceeds Renminbi (RMB) 200,000 Yuan  (P < 0.001), higher parental education level (P < 0.001), daily hours of outdoor activities ≤ 2 h (P < 0.001), and have higher level of height, weight as well as BMI (P < 0.001) but lower refractive status (P < 0.001) than those rural students. Further, there is no significant difference in gender (P = 0.062), and daily hours of near-work (P = 0.981) distribution between urban and rural students.In our study, the seven schools had a total student of 4,583 individuals 6–18 years old, and all of participants were given offers to accept the body and eye examination. In total, 4,522 students  participated in the all examination, corresponding to an overall response rate of 98.7% . Socio-demographic characteristics were compared between urban students and rural students . The rurvs. 5.41%, P = 0.013). However, the age, gender-adjusted prevalence of hyperopia in the rural students was higher than that in the urban students . Additionally, no difference was found in astigmatism between the rural and urban students .Crude and adjusted-prevalence of REs distributed by region is shown in P < 0.05). However, students‘ age, region of habitation, average parental refractive error, annual household income and daily hours of near-work were associated with hyperopia . Further, students‘ age, gender, region of habitation, average parental refractive error, parental education level and daily hours of near-work were associated with astigmatism . In addition, there was a significant correlation between age, region of habitation, annual household income and anisometropia .Bivariate analysis showed factors associated with REs among all subjects . CurrentP < 0.001), 0.53 , 1.07 , and 1.37 , respectively. However, there is no significant difference on presence of astigmatism between students in rural and urban settings . In model 2 adjusting with age, gender and any variables analyzed significantly in the bivariate analysis (P < 0.001) times more likely to be myopic, 1.29  times more likely to be anisometropia, but 0.54  times less likely to be hyperopia. Further, there was no significant association between the student's area of residence and astigmatism .Stepwise multiple logistic models were used to analyze the correlation between region and REs . In modeanalysis , studentP < 0.001). Increasing age, daily hours of near-work and lower annual household income were independent risk factors for hyperopia in the urban participants while increasing age, daily hours of near-work and average parental refractive error were independent risk factors for hyperopia in the rural participants . Female gender was found to be reduced risk for astigmatism in the urban population (P < 0.001). Further, increasing age (P < 0.001) and average parental refractive error (P < 0.05) were independent risk factors for astigmatism in the urban participants. However, increasing age, higher level of annual household income, parental education level and with average parental refractive error were independent risk factors for astigmatism in the rural participants .Bivariate and multivariate analyses identified the risk factors for the presence of any REs in the urban  and ruraP < 0.05).For anisometropia, we found that only increasing age was a risk factor for urban students but both increasing age and higher level of annual household income were risk factor anisometropia in the rural students (all Currently, our study provides the population-based cross-sectional data on the region-specific prevalence of REs and its associated risk factors among the urban and rural school children and adolescents across several gradients of age groups which have different socio-cultural factors in Northeast China. First, our findings revealed that the students living in urban setting have higher prevalence rates and risk for myopia and anisometropia than students living in rural, while the prevalence and risk of hyperopia in the urban students was lower than that in the rural students. Moreover, there is no difference on the prevalence and risk of astigmatism between the urban and rural students. Secondly, the prevalence disparities of REs may be due to the various factors between rural and urban areas. Thirdly, there appeared to be significant difference in factors of REs between study participants residing in urban and rural settings.Consistent with our findings, a previous meta-analysis reported that children from urban environments have 2.6 times the odds of myopia compared with those from rural environments . SimilarTo date, there are few studies investigating the different associated factors for REs between rural and urban participants. The current study performed in Dalian reports the effect and possible factors on REs in a wide age range among the Chinese urban and rural students. For both rural and urban students, we found that increasing age and longer daily hours of near-work were independently associated with myopia, which was consistent with previous reports in Beijing urban students , 40. HowA noteworthy finding is that the prevalence of REs including myopia was not significant with daily hours of outdoor activities in both urban and rural children and adolescents. In contrast, outdoor activities are negatively associated with myopia after adjustment for potential factors in both urban regions such as Hubei  and QingThe major strength of this study included a comprehensive population-based sample from a large city, urban and rural areas; reasonable response rates; and reliable demographic data. This data are extremely useful for healthcare providers to develop long-term strategies to combat avoidable visual impairments due to REs. It is heartening to see a declining prevalence of REs as compared to epidemiological studies done in past worldwide. The study also found socio-demographic and health-related factors for REs between rural and urban students. It is possible that modulating this variable may control the occurrence of RE, however, this warrants longitudinal studies. A limitation of the study is the inability to validate the causal relationship between the significant risk factors and presence of REs. Cohort studies are recommended for the future. In addition, we excluded those participants with optical correction using othokeratology which may lower-evaluating the prevalence of myopia.Our study investigated the overall prevalence of REs including myopia, hyperopia, astigmatism and anisometropia in rural and urban areas in Dalian China in children and adolescents aged 6–18 years. The students with urban habitation had a higher prevalence of myopia and anisometropia but a lower risk of hyperopia than those with rural habitation. With multivariate logistic regression, the factors regarding REs between rural and urban participants were different. Herein, the implementation and findings from this screen will guide the efficient prevention strategy of refractive error and eye care services in urban and rural school children and adolescents.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of Dalian Third People's Hospital. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.LZhan, LL, XM, JW, and WL contributed to the conception of the study. YW, ZL, YQ, JW, YL, WL, YX, NZ, LJ, LW, JS, JY, and LZhao performed the experiment. YW, LL, XR, and LZhan contributed significantly to analysis and manuscript preparation. YW, LL, and XR performed the data analyses and wrote the manuscript. LZhan, LL, and XM helped perform the analysis with constructive discussions. All authors contributed to the article and approved the submitted version.This study was supported by Dalian Health Commission Department; Ministry of Education of Dalian. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


We aimed to evaluate and compare the impact of COVID-19 lockdown on lifestyle changes and other common related effects of the lockdown in Saudi adults with diabetes mellitus (DM), both type 1 (T1D) and type 2 diabetes (T2D).265 T1D and 285 T2D individuals were included in this cross-sectional survey during lockdown using an online questionnaire and compared with 297 participants without DM. Variables included demographics, treatment changes, use of supplements, change in sleeping habits and physical activity, dietary changes, social and mental health, and education and awareness during COVID-19 lockdown.p = 0.003). More participants with T1D and T2D than the control group reported that they felt symptoms of depression during lockdown  and that lockdown affected them psychologically . More participants with T1D than controls reported that their physical activity decreased during lockdown . Furthermore, significantly lesser participants in both DM groups than controls agreed that the health education regarding COVID-19 covered everything . Regarding dietary habits, the DM groups reported more changes in either the number of daily meals, meal content, or mealtimes than the control group.The COVID-19 lockdown was associated with more treatment doses in people with T1D but not in those with T2D (COVID-19 lockdown-associated lifestyle changes were more prevalent in individuals with T1D and T2D compared to control. Findings may assist public health authorities in outlining their responses in pandemics and promote healthy lifestyle adaptations in this high-risk cohort to limit adverse effects in future lockdowns. In December 2019, Wuhan became the first city in China to record some unidentified pneumonia cases, which was later declared a global pandemic, referred to as the COVID-19 pandemic, by the World Health Organization (WHO) . CoronavBy and large, the global population has had an unprecedented experience of the measures taken by the governments and the local authorities to mitigate the health impact of this pandemic . In the Consequently, poorly controlled DM is a risk factor for several infectious diseases . FurtherThe research related to COVID-19 infection and the effects of resulting lockdowns is a rapidly evolving field at a global level. Several studies have reported the impact of COVID-19 on DM patients, implying that COVID-19 may increase the complications of the disease among those with DM , 27. COVIt is reasonable to assume that COVID-19 lockdown and associated restrictions may have altered dietary habits, physical activity levels, mental wellbeing, treatment plans, ease of getting medicines and medical advice on time, and sleeping patterns in patients with DM , 33, howIn KSA, an online electronic survey during the COVID-19 pandemic lockdown was conducted between March 23 and June 20, 2020. This survey was done in collaboration with the Saudi Charitable Association of Diabetes (SCAD), which provides healthcare services to the diabetes population in KSA. The population chosen for our study was the subscribers of SCAD from different regions  in KSA. Participants voluntarily joined in this survey, and individuals with diabetes all vary in the disease's progression and treatments. The inclusion criteria included adult Saudis who were in KSA during the lockdown and had access to the internet. In addition, those with previously diagnosed diabetes were categorized as T1D or T2D groups, and the rest of the respondents with no history of diabetes were categorized as the control group. There were no additional exclusion criteria other than failure to complete the questionnaire.Ethical approval for this study was obtained from the Ethics Committee for Scientific Research and Post Graduate Studies at the College of Science, King Saud University (KSU), Riyadh, KSA. The online electronic survey also included the informed consent form, which had to be agreed upon by the respondents before participating in the survey.A standardized questionnaire was adapted from earlier studies , 34–36, This section included questions for getting demographic and anthropometric data, where information on participants' gender, age, weight, height, and the region was asked , and an average value of scores for all the items in each section was presented as mean ± standard deviation.Sample size calculation was done using Raosoft online. The sample size needed was calculated using an error margin of 2.5%, and the prevalence of T1D and T2D was 0.03 and 18.3%, respectively. To get a confidence level of 95%, a minimum of 500 sample size was set to achieve the study's objectives. All calculations and data analysis was done using SPSS version 16.5. The data in three study groups were compared using chi-square test for categorical variables and the independent student's p < 0.05.Logistic regression analysis (univariate and multivariate) was run separately with T1D/T2D versus control as dependent variable and close-ended questions as independent variables. In the multivariate model, adjustment was made with age, gender, BMI, and demographic variables. A 95% confidence interval (95% CI) for the odds ratio (OR) was checked to evaluate significant independent categorical variables. Statistical significance was set at p < 0.001). Majority of all participants (about 50%) were from the central region. The control group also had the highest prevalence of employed participants (be it working remotely or in-person) than DM groups with a higher prevalence of “retired from work” participants.via yes/no questions. As expected, most DM groups took medications with higher proportions of insulin and oral hypoglycemic pills in the T1D and T2D groups, respectively (p < 0.001 for both). Dietary and weight loss management were overwhelmingly from the control group. The use of dietary supplements such as vitamins D, C, and zinc was highest in the control group . There was no difference in the use of supplements between the DM groups. When asked whether sleeping hours increased during the lockdown, less than half in all groups  said “yes,” and a small number indicated that they were on sleeping pills. Participants whose exercise decreased during lockdown were highest in the T2D group (47.0%). Those with <10 min/per day of exercise were higher in T2D than T1D participants (p = 0.009). When asked if they were infected with COVID-19, around 15% of study groups answered “yes.” There was no difference in the prevalence of opting for different COVID-19 symptoms experienced.p < 0.001 for all). No difference was observed between groups related to changes in social and mental health issues during the lockdown. Lastly, the majority (>55%) agreed that health awareness campaigns by SCAD for COVID-19 were carried out previously. A lower proportion in both diabetes groups than control agreed that awareness campaigns covered all aspects of COVID-19-related information and that they maximized the information given (p < 0.01 in both).p-values, has been provided as Multinomial logistic regression was done to examine differences between DM and control groups in the responses. Only significant independent variables were plotted as a forest plot in The consequences of COVID-19 lockdown on the lifestyle of the general population and high-risk groups have been the area of interest because of this pandemic's massive impact on humankind. However, less has been investigated primarily in this population, where there is a huge prevalence of diabetes. Therefore, the present study aimed to evaluate and compare lifestyle changes due to COVID-19 lockdown in a population of adult Saudis with T1D and T2D. The study suggests lifestyle changes in terms of dietary, physical activity, sleeping hours, etc., were more prevalent in diabetes groups compared to the control. Also, the DM groups reported higher prevalence of insufficient health education and awareness related to COVID-19. Besides, the self-assessed changes in the psychological status of the respondents, like insomnia and depression, were also reported by a sizable proportion in all groups.Diabetes, a chronic disease, is highly prevalent in this part of the world  , and it A large proportion of participants indicated that they had insomnia (>35%) and irregular sleep (>55%) during the lockdown. Besides, fewer subjects in the T2D group reported that the sleeping hours increased during lockdown compared to the T1D group. These results align with multiple studies that reported an increase in insomnia during COVID-19 lockdown –44. The Physical activity and exercise rates decreased during the lockdown in all groups. Apart from the glycemia-controlling medicines, exercise training programs especially aerobic exercises, have emerged as a useful tool in managing diabetes . In lineThe dietary guidelines announced by the World Health Organization to boost immunity during the COVID-19 outbreak included taking a balanced diet with the recommended amount of macro and micronutrients; however, the literature suggests that the lockdown resulted in less consumption of fresh produce and more consumption of comfort foods . This maThe results of this study could help health authorities and diabetes organizations like SCAD, which provide health care services to people with diabetes in Saudi Arabia, better handle these services in the event of a pandemic. According to the American Diabetes Association, conventional diabetes care for patients involves glucose management and monitoring, timely advice on food and physical exercise, availability, and distribution of medicines, and efforts to prevent infection in high-risk populations. This lockdown taught us a lot about how to better handle a future pandemic by showing us what not to do when it comes to access and availability of glycemic monitoring supplies like glucose strips, glucometers, and needles, among other things. In the event of future pandemics, findings of this study on dietary supplements may assist DM management organizations in emphasizing the need to focus on logistics to ensure that there are enough dietary supplements available and that these supplements are disseminated to patients. Participants in both DM groups believed that COVID-19 information was insufficient, which might assist the authorities in creating better lifestyle interventions for diabetics and other high-risk persons in future pandemics. The Findings on depression and the psychological effects of lockdown in diabetics may also help these organizations develop solutions for mental health, anxiety levels, the significance of enough sleep, and so on in high-risk individuals.The strengths of the study included a relatively large number of respondents and the subjects recruited from different geographical regions of KSA. To the best of the authors' knowledge, this study is the first report of lifestyle changes during COVID-19 lockdown in both T1D and T2D Saudi subjects. At the same time, the authors would like to acknowledge some limitations which should be considered in interpreting the study findings. Firstly, this study was cross-sectional, which might introduce a potential risk of recall bias. However, our study intended to be a comparison analysis between the study groups. Secondly, participants in this study self-reported lifestyle changes during lockdown with no specific personality assessment like ones for psychological statuses like insomnia and depression, and they might have underestimated these changes. Thirdly, members of SCAD were recruited as participants for the study, which might have had some bias in the socio-economic class of overall Saudi subjects. Nevertheless, the study revealed some important findings about lifestyle changes in DM individuals during pandemic. The findings may help the concerned authorities and organizations prioritize interventions to handle DM management in future lockdowns.Our results show that the lockdowns imposed as restrictive measures against COVID-19 negatively affected the lifestyle and daily habits of Saudi individuals with DM. The present findings should help public health authorities and stakeholders involved in diabetes care to plan for future pandemics and promote healthy lifestyle changes in high-risk populations during lockdowns.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Ethics Committee of the Post-Graduate Studies, College of Science, King Saud University. The patients/participants provided their written informed consent to participate in this study.NA-D, AA, and SS designed the study. DA and GA worked on the methodology. MK did the statistical analysis. AA, HA, AA-H, and DA helped in the data curation. AA and KW wrote the first draft. NA-D, HA, and SS revised the manuscript. NA-D, NA, and HA did the study supervision. All authors contributed and approved the final version of the paper.This research was funded by the Deanship of Scientific Research, King Saud University for funding through Vice Deanship of Scientific Research Chairs, Chair for Biomarkers of Chronic Diseases.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Multiple sclerosis (MS) has two pathophysiological processes, one inflammatory and the other degenerative. We investigated the relationship between active lesions on magnetic resonance imaging showing the inflammatory phase in MS patients and serum parameters that can be used as inflammatory biomarkers. Thus, we aim to detect the inflammatory period in clinical and radiological follow-up and to reveal the period in which disease-modifying treatments are effective with serum parameters.One hundred eighty-six MS patients presented to our hospital between January 2016 and November 2021 and 94 age- and sex-matched healthy volunteers were recruited for our study. While 99 patients had active lesions on magnetic resonance imaging, 87 patients did not have any active lesions. Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and monocyte/lymphocyte ratio (MLR) were determined. The SII (systemic immune inflammatory index) value was calculated according to the platelet X neutrophil/lymphocyte ratio formula.NLR, MLR, PLR and SII values were found to be statistically significantly higher in MS patients than in the control group. The NLR, MLR, PLR and SII were higher in the active group with gadolonium than in the group without active lesions. In addition, the cutoff values that we can use to determine the presence of active lesions were 1.53, 0.18, 117.15, and 434.45 for NLR, MLR PLR and SII, respectively.We found that all parameters correlated with radiological activity. In addition, we showed that we can detect the inflammatory period with high sensitivity and specificity with the cutoff value used for SII and PLR. Among these easily accessible and inexpensive evaluations, we concluded that SII, including the values in the PLR formula, can come to the fore. Multiple sclerosis (MS), a chronic inflammatory demyelinating disease, is a disorder of the central nervous system (CNS) that most commonly causes disability in young adults after trauma , 2. GeneCNS inflammation and neurodegeneration, which occur with activation of innate and acquired immune cells triggered by autoimmunity, play a role in the pathogenesis of MS , 6. ThesThe differential count of white blood cells is a widely used biomarker to indicate systemic inflammation. Many ratios, such as neutrophil/lymphocyte (NLR), platelet/lymphocyte (PLR), and monocyte/lymphocyte (MLR) ratios, obtained by dividing the cell counts by each other, which are thought to be superior to the use of white blood cell subtypes alone in demonstrating inflammation, are currently in practice . For exaThe systemic immune-inflammatory index (SII), which is calculated according to the peripheral platelet count X neutrophil count/lymphocyte count formula, has been used to determine the prognosis in many cancer types, especially hepatocellular cancer and other diseases that progress with changes in inflammatory backgrounds , 17. HowIn this study, NLR, PLR, MLR and SII levels were planned to be evaluated in both patient groups with active contrast-enhancing lesions and without contrast enhancing lesions groups on MRI and in healthy controls. In this way, we investigated whether the inflammatory process in which DMT drugs are effective (with the idea that gadolonium involvement in MRI reflects inflammation) can be detected in the blood through NLR, PLR, MLR and SII values as well as whether it can be used as a biomarker in terms of prognosis and disability.There have been some concerns about the use of gadolonium recently. In particular, the accumulation of this substance in the brain and its neurodegenerative consequences have been discussed . In addiIn our study, patient records from January 2016 to November 2021 were reviewed retrospectively. One hundred eighty-six patients who presented to our hospital and who were diagnosed with relapsing remitting MS by two neurologists and 94 age- and sex-matched volunteers who gave blood for other reasons were recruited for our study. Evaluation of the data was performed in 2021. The 2010 McDonald's criteria were used to diagnose MS. The McDonald Criteria 2010 was revised at the end of 2017 , but sinPatients with contrast-enhancing lesions after gadolinium injection (Gd+) were included in the patient group with active lesions. Patients who did not have any Gd+ lesions were included in the patient group without active lesions. While the number of patients with active lesions in the patient group was 99, the number of patients without active lesions was 87. The EDSS value  was used to evaluate the disability of the patients. Disease duration was calculated on the basis of the time of initial diagnosis of the patient, and the treatments received by the patients were those they were receiving at the time of blood collection. Disease-modifying therapies act with different mechanisms of action. For example, while interferons may cause lymphopenia, lymphocytosis may occur with natalizumab, which controls lymphocyte passage to the central nervous system , 21.Therefore, we included patients at the time of initial diagnosis, patients who did not receive treatment, patients who took medication not affecting lymphocyte, neutrophil, monocyte and platelet counts and those with no history of immunosuppressant treatment.The rights of all participants were protected according to the Declaration of Helsinki. Patients under 18 years of age, patients with active infection, diabetes mellitus, hypertension, acute/chronic liver or kidney failure, active or chronic inflammatory disease , other autoimmune disease, pregnant patients, patients with existing malignancy, and patients with a history of surgical intervention, acute myocardial infarction or trauma over the last 3 months were not included in our study.The control group was randomly generated from 94 age- and gender-matched people who applied to our outpatient clinic between 2016 and 2021, did not have any complaints or systemic diseases and were asked to document that they were healthy.Ethics committee approval of our study was obtained from Sivas Cumhuriyet University Non-Interventional Ethics Committee on 21.10.2020 under number 2020-10/23.Dry tubes were used for biochemical analysis, and EDTA tubes were used for hematological tests. Complete blood count analysis of blood samples taken from the left antecubital vein of the subjects at rest was performed using Diagon kits on the Mindray BC-6800 device, and kits from the same company were used with the fully automatic nephelometric method on the Beckman Coulter AU5800  device for biochemical analyses. In our clinic, if any imaging containing gadolonium is to be performed, we have a practice in which kidney function tests are requested on the same day. In addition to this test in MS patients, complete blood count, sedimentation, CRP, Vitamin D, folic acid, Vitamin B12, and thyroid function tests were added. Therefore, blood samples taken within 24 hours were included in the study without storage and were evaluated within the same day.NLR, PLR and MLR values were obtained by dividing the cell counts in the measured complete blood count by each other. The SII value was calculated according to the platelet X neutrophil/lymphocyte formula.Cranial images obtained by the Department of Radiology of Sivas Cumhuriyet University on Siemens brand Magnetom Aera 2013 Model 1.5 Tesla magnetic resonance imaging device were evaluated with the automation system over the Sectra Uniview system. Demyelinating lesions with contrast enhancement after gadolinium injection (Gd +) in the T1 examination of these MR images in the axial, coronal and sagittal planes were defined as active lesions. The presence of active lesions was evaluated by an independent radiologist and neurologist, and patients were included in the patient group with active lesions accordingly. The other patient group without active lesions consisted of patients who did not have Gd + lesions. Additionally, the patients with active lesions were divided into 3 groups by the number of lesions they had .p<0.05.NCSS  2007  was employed for statistical analyses. The conformity of the quantitative data to the normal distribution was tested with the Shapiro‒Wilk test and graphical examinations. Whether the distribution of continuous data was close to normal was examined with the Kolmogorov‒Smirnov test. When continuous data showed a normal distribution, they were expressed as the mean ± standard deviation (SD); otherwise, they were expressed as the median and minimum-maximum, while categorical data were expressed as frequencies and percentages. During the comparison of quantitative data, Student’s t test was used to compare two groups showing a normal distribution, and the Mann‒Whitney U test was used to compare two groups not showing a normal distribution. One-way analysis of variance and binary evaluations with Bonferroni correction were used to make more than two intergroup comparisons of normally distributed quantitative variables. The Kruskal‒Wallis test and Dunn-Bonferroni test were used for comparisons between groups of more than two nonnormally distributed quantitative variables. Fisher-Freeman-Halton exact test was used to compare qualitative data. Spearman correlation analysis was employed to evaluate the relationships between quantitative variables. Diagnostic screening tests  and ROC curve analysis were used to determine the cutoff. Statistical significance was accepted as The sample size and power analysis of the study were made with the G*Power 3.1 test program. The sample size was determined by reference to the studies of Demirci et al. Assuming ∝=0.05, effect size d=0.65, 87 MS patient groups and 47 control groups were calculated for 0.95 (1-β) power. However, since our study was designed retrospectively, it was conducted with 186 MS patients and 94 control groups. The power of our study was calculated as 0.99 in Post Hoc analysis , 23.n=206) female and 26.4% (n=74) male. The group of patients was divided into two subgroups: patients with and without active lesions. In the group of patients with active lesions (n=99), 73.7% (n=73) were females, while in the group without active lesions (n=87), 78.2% (n=68) were females. This rate was 69.1% (n=65) in the patients in the control group. There was no difference in sex among the three groups (p=0.392). The mean age was 33.85±9.6 years in the patient group with active lesions (n=99) and 32.72±7.4 years in the group without active lesions. The mean age was 33.44±8.0 years in the patients in the control group. There was no difference among the three groups in terms of sex or age (p=0.656). When the number of lesions in the patient group with active lesions was analyzed, the number of lesions was between 1-5 in 54.5% (n=54), between 6-10 in 16.2% (n=16), and between 11 and above in 29.3% (n=29). When the localizations of these lesions were analyzed, it was determined that 77.8% (n=77) were supratentorial, 17.2% (n=17) were infratentorial, and 5.1% (n=5) were spinal. The disease period in this patient group changed between 0 and 22 years, and the mean disease period was 5.05±4.65 years. EDSS measurements changed between 0 and 6 values, and the mean was 1.11±0.49. %54.3 (n=101) of the patient group was under treatment during this study. In terms of laboratory parameters, the patient group had high monocyte, platelet, and neutrophil counts, while the control group had a statistically significantly higher lymphocyte count (p=0.001). When the patient group was divided into 2 groups according to the presence of active lesions, the number of monocytes, platelets and neutrophils in the group with active lesions was found to be statistically significantly higher than that in both the patient group without active lesions and the control group . Additionally, the number of lymphocytes in the group with active lesions was found to be significantly lower than that in both the patient group without active lesions and the control group (p=0.001). There was no statistically significant difference between the patient and control groups in terms of CRP measurements and eosinophil counts . When the MLR, PLR, NLR and SII ratios were examined, all 4 ratios were found to be statistically significantly higher in the patient group versus the control group (p=0.001). Similarly, MLR, NLR, PLR and SII values in patients with active lesions were statistically significantly higher than in patients without active lesions, according to the analysis of the subgroup in the patient group  (Table p=0.042), but there was no difference in terms of the MLR, NLR and SII values between the two groups.The research was conducted between January 2016 and November 2021 in Sivas Cumhuriyet University Hospital, Department of Neurology, with a total of 280 cases, 73.6% , the cutoff value for PLR was 115.59 , the cutoff value for NLR was 1.36 , and the cutoff value for SII was 412.53  . However, there was no statistically significant relationship between EDSS score and MLR, NLR and SII measurements . Additionally, there was a weak positive and statistically significant relationship between disease duration and PLR measurements in the patient group . However, there was no statistically significant relationship between disease duration and MLR, NLR or SII measurements . Similarly, no statistically significant correlation was found between lesion localization or lesion number and MLR, PLR, NLR, and SII measurements in the patient group  .In the patient group, there was a weak positive and statistically significant relationship between EDSS score and PLR measurements . Although the exact cause of MS is unknown, it is thought to have a multifactorial etiology, primarily environmental and genetic factors. While HLA variant HLA-DRB1*15:01, one of genetic factors, is kept responsible, environmental factors such as Epstein bar virus infection, low vitamin D level or smoking are also on the list . There aIt has been shown through EAE models that neutrophils can act on the brain parenchyma by disrupting the BBB and increasing inflammation in MS. Neutrophils, which are short-lived cells, have been found to be highly expressed in MS patients at the onset of disease and relapse. In particular, neutrophils are thought to contribute to the pathological process by affecting the periphery rather than the CNS. In light of this information, myeloid cells such as neutrophils seem to be a target for future treatments, follow-up and monitoring . Recent The radiological and histological indicator of MS disease is demyelinating plaques. Significant activation of microglia is present at the edge of active demyelinating lesions, while macrophages are at the lesion center, and it is unknown whether they are derived from a pool of activated microglia or from hematogenous monocytes. Similarly, a high number of microglia are present in the periplate and even in the distant, normal-appearing white matter . MS plaqPlatelet abnormalities in MS patients were reported decades ago , 41. NewSII, a new indicator calculated by combining the information from all three of the platelet, neutrophil and lymphocyte counts, has been recently shown to be an independent risk factor in determining the severity of the disease and short-/long-term prognosis in acute cerebrovascular events , 46. TheThe NLR, MLR, PLR and SII, which we found to be higher in patients with active lesions, seem to be important in terms of indicating the inflammatory period of MS patients. In addition, according to the results of our study, it can be suggested that the presence of active lesions can be detected without using gadolinium with the cutoff value we determined for MLR, PLR, NLR and SII in patients with active lesions on MRI based on the results of our study. Among these rates, the SII value, including PLR, becomes prominent because it combines information from three blood parameters, unlike other inflammatory indicators obtained by the rate of two blood parameters, and it has high susceptibility and specificity.It has recently been shown that gadolinium, which is the contrast agent for MRI that is frequently used in the monitorization of MS patients, can accumulate in many tissues, especially in the brain, and may have long-term toxic effects . TherefoOur study has several limitations. First, our study was designed retrospectively. Therefore, only the leukocyte count and CRP level were evaluated among the inflammatory markers, and the levels of other inflammatory markers could not be measured. This did not allow us to make further comments on the highly complex pathophysiology of MS. Similarly, only patient sera were used in our study, and inflammatory indicators in CSF could not be evaluated. In addition, only patients with radiological activity in the presence of gadolinium were included in our study, and more sensitive studies could not be performed. While determination of attack frequency and disability is clinically important for follow-up and treatment monitoring in MS patients, radiological evaluation is another vital parameter. The inflammatory process is thought to continue in an exacerbated form in radiologically active patients. The high level of new inflammatory biomarkers in our study in patients with active lesions also lends support to this information. Patients benefit more from treatment in this phase of the disease rather than in the chronic neurodegenerative phase, and the disability rate of patients who receive effective treatment decreases in the following period. SII, an important inflammatory biomarker in MS pathophysiology that combines information from platelet, neutrophil and lymphocyte counts, which was found to be correlated with radiological activity in our study, can be considered an easily accessible option that does not require additional cost in the follow-up of MS patients and treatment monitoring in the inflammatory phase, during which MS medications are more effective. In addition, our results, which are a reflection of radiological activity, may be an alternative option for the use of gadolinium. Further studies in larger patient series and subgroups are required to support this information and make more interpretations.


Despite our significantly evolved understanding of BHD over the past decades, no bibliometric analyses have been conducted in this field. This study aimed to analyze and visualize the characteristics of publication outputs, the research hotspots, and scientific frontiers about BHD using bibliometric analysis.Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant inherited disorder caused by germline mutations in All relevant literature on BHD was culled from the Web of Science Core Collection (WoSCC) database. Valid data were extracted from the articles and visually analyzed using CiteSpace and VOSviewer.Plos One was the journal with the highest publication outputs, and half of the top 10 journals and co-cited journals belonged to Q1 or Q2. Keyword citation bursts revealed that management, tumor suppressor, flcn gene, spectrum, diagnosis, risk, computed tomography were the emerging research hotspots.A total of 751 qualifying papers were included. Publication outputs concerning BHD increased over time. The dominant position of the United States and Japan in BHD research field was evident. National Cancer Institute (the USA) and Yokohama City University (Japan) were the two most productive organizations. W. Marston Linehan exerted a considerable publication impact and had made the most remarkable contributions in the field of BHD. FLCN-associated pathways involved in the pathogenesis of BHD, specific options for early diagnosis, and molecular-targeting therapies will remain research hotspots in the future.Research on BHD is prosperous. International cooperation between countries and organizations is also expected to deepen and strengthen in the future. Our results indicated that  Birt-Hogg-Dubé syndrome  is an inherited autosomal dominant disorder that may involve multiple organs including the skin, the lung, and the kidney. This syndrome was actually first described in 1975 by Otto P. Hornstein and Monika Knickenberg from Germany. They pointed out that the occurrence of multiple “perifollicularfibromas” represented an autosomal dominant trait indicating extracutaneous cancer proneness . Then, tFLCN gene, encoding the protein folliculin, was identified as the causative gene of BHD  . BHD is e of BHD .The clinical expression of BHD typically includes cutaneous fibrofolliculomas, multiple pulmonary cysts, recurrent spontaneous pneumothorax, and renal tumors of various histological types . Early dBibliometric analysis is the use of mathematical and statistical methods to analyze large amounts of heterogeneous literature . CombiniAll historic achievements were culled from the Web of Science Core Collection database. Editions selected “Science Citation Index Expanded (SCI-EXPANDED)”. The search string was set to TS = (“Birt-Hogg-Dubé Syndrome” OR “BHD” OR “Hornstein–Knickenberg Syndrome”). The publication period was limited from 2001 to 2021. Of various publication types, only articles and review articles written in English were included. Record content chose full record and cited references. Then exported and saved the record as plain text files, and stored in the format of download_txt. The whole process was completed within 1 day .Coherent data were imported into CiteSpace and VOSviewer to perform visual analysis. In the atlas, circles stand for countries/regions, organizations, authors, and keywords; lines between circles represent collaboration or co-citation relationships; a spectrum of colors depicts the temporal order of observations.CiteSpace version 5.8.R3  was used to visualize the intercountry and institutional analysis and the author's cooperation. Developed by Chen, Citespace is an application for progressive knowledge domain visualization . It is eVOSviewer version 1.6.17  was chosen for drawing the maps of the references and journal co-citation analysis, as well as keyword co-occurrence. Unlike the conventional tools for building and viewing bibliometric networks, VOSviewer focuses on the graphic representation of knowledge mappings. It is particularly useful to display sizable bibliometrics in an easy-to-explain way .h-index of all papers was 66. 2021 was the peak year of publication outputs with 61 articles.As shown in n = 250, 33.3%), followed by China , Japan , England  and Italy . The outputs from the two most productive countries were nearly half of the total. Organizations with the highest number of papers were National Cancer Institute (the USA), and Yokohama City University (Japan) ranked second. Countries such as Italy, Canada, France, Spain, the USA, Japan, and China had a high degree of centrality, as indicated by the nodes' purple outer rings in The maps of intercountry  and inteCo-cited authors are two or more authors who are cited together by later publications, and they build a co-citation relationship. Eight authors had a citation frequency of more than 200 times. JR Toro (425) was the most frequently cited author, followed by LS Schmidt (370).446 academic journals were involved in the BHD research field. Plos One contributed the majority of articles , and Proceedings of the National Academy of Sciences of the United States of America (PNAS) had the highest impact factor among the top 10 journals.PNAS had the highest level of co-citations (666), followed by Journal of Medical Genetics (653). As shown in The number of times that an academic journal is co-cited, is one of the indicators to measure whether the journal has notable influence in a domain. Four journals had been co-cited more than 500 times among the top 10 co-cited journals. Cancer Cell by ML Nickerson in 2002 (Co-citation implies that two or more articles are cited simultaneously by more than one later publication. It is a quantification to measure the degree of relationship between references.  in 2002 . The majfolliculin (83), BHD gene (68), tumor (67), cancer (66), fibrofolliculoma (66).Research topic and essences are summarized by keywords. High-frequency keywords generally are the dominant research direction. Keyword co-occurrence analysis offers assistance to find research hotspots and predicts research trends in a certain field . AccordiClustered keywords reflect knowledge structure in a particular topic. We use VOSviewer software for this process. Nodes and labels constitute a unit, and units with different colors make up different clusters. There are red, green, blue, and yellow clusters as shown in folliculin (8.16), acrochordon (7.56). Besides, keywords such as “management”, “tumor suppressor”, “flcn”, “spectrum”, “diagnosis” turned up constantly during the past 5 years  ranked the first, followed by Italy (0.53); National Cancer Institute (the USA) and Yokohama City University (Japan) were the top two organizations of publication outputs, as well as centrality, which reveals they played key parts in BHD research field and bridged in the network of global cooperation. However, from FLCN, the causative genes for BHD in 2002 , followed by Laura S Schmidt 39, 5.2%), Mitsuko Furuya , Masaya Baba , and Berton Zbar . It is noteworthy that W. Marston Linehan had the highest citations , which indicates the most outstanding contributions he had made in the field of BHD during the last 20 years. Dr. Linehan is chief of the Urologic Oncology Branch at the National Cancer Institute, part of the National Institutes of Health in the United States. Since pioneering the research of the genetic basis of kidney cancers, Dr. Linehan and his team have identified six renal cancer genes and five new inherited kidney diseases including BHD. By studying patients and families with kidney cancer , 23, he , 5.2%, M in 2002  and prov02 , which reported FLCN gene was identified as the causative gene of BHD. This pioneering finding considerably changed our concepts of the pathogenesis of BHD.As shown in folliculin (83), BHD gene (68), cancer (66), fibrofolliculoma (66), pulmonary cyst (40), diagnosis (39), management (36), and tumor suppressor gene (33) were keywords with high occurrence frequency. Cluster analysis based on keywords eventually generated four clusters. According to these two analyses, we determine the research hotspots and frontiers in the field of BHD. The four main contents are summarized as follows:Keyword co-occurrence analysis aims at comprehending the distribution and development of research hotspots in a specific field. As demonstrated in FLCN remains the only gene involved in BHD to date. Although the exact function of this tumor suppressor gene remains incompletely resolved, it is believed to be involved in the modulation of cell growth, proliferation, and survival through the mammalian target of rapamycin (mTOR) signaling pathway  showed that lung function at baseline was not affected except for slightly increased residual volume (RV) and reduced carbon monoxide (DLco), and no significant deterioration of lung function during 6-year follow-up .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Despite being usually delivered in oncological patients, radiotherapy can be used as a successful treatment for several non-malignant disorders. Even though this use of radiotherapy has been scarcely investigated since the 1950s, more recent interest has actually shed the light on this approach. Thus, the aim of this narrative review is to analyze the applications of non-oncological radiotherapy in different disorders. Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. This review contains a narrative report and a critical discussion of non-oncological radiotherapy approaches. In conclusion, non-oncological radiotherapy is a safe and efficacious approach to treat several disorders that needs to be further investigated and used in clinical practice. Radiation therapy (RT) represents one of the cornerstones of cancer management, together with surgery and systemic therapy. It is reported that almost half of all cancer patients will receive RT during their treatment .In the last decades, RT has undergone several advances driven by the increase in knowledge of radiobiology, use of advanced imaging, and treatment delivery approaches ,3,4,5. Actually, RT can be delivered with great accuracy, to reach an increasing dose to the targets and at the same time sparing the surrounding organs at risk ,3.Non-oncological radiotherapy can be used to treat several disorders and accounts for 20% of all treated patients in Germany ,7,8.In many other countries, including Italy, the use of RT for non-oncological diseases is not very common among the RT centers and often unknown among the other specialists.The knowledge and the promotion of non-oncological RT, thus, could counterbalance the expected loss of patients or RT fractions foregone in the next future due to the use of hypofractionation.Herein, we will discuss the different non oncological diseases that can be treated by RT. Following a literature search, we will provide a narrative overview of these topics.A literature search was conducted to retrieve potential eligible studies using PubMed and the clinicaltrials.gov electronic database.The literature search was performed in September 2022 (from 1980 to August 2022) using the keywords “Radiotherapy AND non oncological OR non malignant OR benign“.Additionally, we manually searched the reference lists of studies and review papers to identify other relevant studies. No limits were applied to publication type. The results are grouped according to the non-oncological disorders and discussed qualitatively.Cardiac arrhythmias affected 8.8 million people in Europe and is an independent risk factor for stroke, , heart dStereotactic radiotherapy (SBRT) is under investigation as a treatment option for patients with VT who do not respond to antiarrhythmic drugs and/or catheter ablation. The evidence is scarce, but most studies suggest the dose of 25 Gy in a single session.Cuculich et al. combined techniques of electrocardiographic imaging to map arrhythmogenic scar regions in patients with refractory VT and non-invasive delivery of precise ablation with SBRT to perform noninvasive cardiac radioablation. SBRT dose was a single fraction of 25 Gy. Treatment efficacy was measured using the number of VT episodes recorded by ICDs . Of the Wight et al., similarly, treated with the same dose 14 patients with refractory VT. In this trial, the clinical target volume was delineated according to the individual patient’s characteristics, based on electroanatomic mapping. Two patients died after SBRT, whereas one received a heart transplant, and another patient did not respond. Of the other 10 patients, VT was reduced in 59%, ATP was reduced in 39%, and shocks were reduced in 60% [In the UK multicenter experience, seven patients were treated with the same dose and technique similarly to the previous experience. After 6 months, for the five patients analysed VT burden was reduced by 85%, with no high-grade acute toxicity and three deaths due to heart failure. .The STRA-MI-VT was a phase Ib/II trial that evaluated the feasibility of Cyberknife tracking in treatment planning .Bonaparte et al.  also per4Dphantom . Simulations showed that cardiac motion decreased the target’s D98% dose between 0.1 and 1.3 Gy, with gating providing effective mitigation. So, real-time MRI-guided cardiorespiratory motion management greatly reduces motion-induced dosimetric uncertainty and warrants further research and development for potential future use in STAR aimed at simultaneously compensating cardiac and respiratory motions [A systematic review including 13 studies and 57 patients confirmed efficacy and safety of STAR for refractory VT/ventricular fibrillation (VF). Thirty-one patients (54%) had ischemic cardiomyopathy and fifty patients (88%) had prior catheter ablation (CA) for VT/VF. A single dose of 25 Gy was delivered to a mean PTV of 64.4 cc (range 3.5–238) with a mean safety margin of 3.3 mm (0–5). Electrical storm was shown in 7% after SABR. VT burden was reduced in all patients, but recurrence affected most of the patients (75%), with several adverse events (81%) and no treatment-related deaths. The authors concluded that STAR preliminary experience appears safe and efficacious despite the recurrence rate and deserve to be further investigated . Despite motions .Kautzner et al. have published case series with the first postmortem immunohistochemical analysis of morphologic changes in the myocardium early and late after SBRT. The authors have found apoptosis followed by fibrosis that could explain the timing of the SBRT efficacy on VT .In conclusion, STAR had reasonable VT suppression in patients where conventional treatment had failed.AF affects about 40 million people in the world and increased the risk of stroke and heart failure. Current clinical management include antiarrhythmic therapy and eventually catheter ablation in drug refractory patients. Despite that, a subset of elderly patients are not responsive to systemic therapies and have an high risk of complications following catheter ablation, thus a non-invasive approach as STAR should be investigated. A systematic review collected available evidence  on the feasibility and efficacy of STAR, including photon RT (XRT) and particle beam therapy (PBT), in the treatment of AF. Twenty-one works  published between 2010 and 2021 were included. The main favorable finding consisted in the detection of electrical scar in 4/4 patients undergoing specific evaluation, whereas the minimum dose for efficacy was 25 Gy. No acute complications were observed below this dose and a great heterogeneity was observed among the included studies .Di Monaco et al. performed a phase II trial that reported a preliminary experience of five patients treated for AF. The preliminary results showed no high-grade side effects and a good response in terms of AF control and no further use of antiarrhythmic drugs .Ultimately, STAR represents a safe and effective non-invasive approach in the treatment of drug-refractory arrhythmias, but there is still poor data in the literature regarding long-term efficacy and follow-up. These two aspects, together with the choice of specific patient settings, represent the most important challenge to be investigated with well-defined studies.Non-malignant, proliferative, soft tissue disorders are a very heterogeneous group of diseases, with a tumor-like phenotype, although they do not have malignant characteristics. These pathologies can reach large dimensions and cause serious organs involved deficits. Abnormal growth of fibroblasts or hypertrophic scar tissue (keloids), or inflammatory factors over-expression, such as bFGF, TGF-β, PDGF, EGF, and CTGF in Dupuytren’s disease, can be found at the basis of the onset of these disorders ,24. RT mKeloids are benign skin disorders based on excessive connective tissue proliferation during the normal scarring process. They typically appear after repeated surgeries at the same site, burns, after trauma, and deep dermis injuries. Pathogenetic mechanisms are not fully known, but the fibroblasts present in keloids have different characteristics compared to the fibroblasts present in normal skin . KeloidsDupuytren’s disease is a fibrotic hyperplasia of connective tissue structures at the level of the finger band and palm. It is a rare condition, with a prevalence of about 2% and with a higher incidence in males (3:1 ratio). The pathogenesis is probably due to factors such as repeated trauma, alcohol and nicotine abuse, and hereditary factors. The diagnosis is purely clinical and sees around the 4th decade of life the presence of fibrotic nodules at the level of the hand that result in digito-palmar contracture leading to severe functional limitations. Dupuytren’s disease can be staged by Tubiana classification, which subdivides pathology according to symptomatology. The gold standard treatments for early stages are medical treatment with intralesional applications of xanthine oxidase/dehydrogenase inhibitor, allopurinol, or cytotoxic agents such as vinblastine or colchicine. Surgery is usually reserved for more advanced stages (Stage 3 Tubiana); the role of RT in the treatment of Dupuytren’s disease tends to be rather preventive and prophylactic than curative. Thus, the goal is to avoid future functional impairment and a future need for surgery . The effPeyronie’s disease (PD) is a benign condition leading to plaque formation at the level of the tunica albuginea of the penis, leading to local pain and a change in curvature during erection. It usually affects men between the 4th and 6th decades of life with an incidence of 0.3–3%. The most likely mechanism is penile trauma causing inflammation of the tunica albuginea and eventually scarring with fibrotic plaque formation. The pathology presents with penile pain, plaque formation, deformity during erection, and subsequent erectile dysfunction. Diagnosis is clinical with identification and measurement of the plaque. Medical treatment involves the use of drugs for oral treatment such as vitamin E, tamoxifen, and colchicine and for intralesional injection verapamil and collagenase. If drug therapy fails, surgery remains the best option, especially in the cases of severe curvature or angulation and erectile dysfunction .Radiation therapy is consolidating over the years its role in the treatment of inflammatory or degenerative skeletal disease. Due to the control of pain, the two most frequent indications for radiotherapy in benign diseases are osteoarthritis and periarthritis. Moreover, RT is a non-invasive approach. Irradiation can be provided by LINAC or orthovoltage. A summary of the collected evidence is reported in Epicondylitis is commonly divided into two main branches: lateral, also commonly known as tennis elbow, and medial, the golfer’s elbow. Epicondylitis has a negative impact on patients quality of life with symptoms such as pain, joint mobility restriction, and even sometimes edema, limiting everyday activities and independence .Hautmann et al.  irradiatAlvarez et al.  have treThe effectiveness of RT is to be found in the anti-inflammatory mechanism of low doses (0.5–1.5 Gy/fx), which determine inhibition of the interactions between leukocytes and endothelial cells, a decrease in the production of adhesion molecules to the endothelium, a decrease of mediators of inflammation, and less expression of pro-inflammatory cytokines. Of note, there is no guideline regarding regimen and dose fractionation, but the strategies have been determined empirically and it has been reported that various doses such as 0.5 Gy performed in six fractions had the same effect of a dose of 1 Gy in six fractions. The choice of fractionation is mostly based on in vitro experiments, which have shown that the anti-inflammatory effect of low doses RT was maximum at 48 h after irradiation, and it was lost after 72 h .In the study of the Netherlands, there were reported negative results for RT, this time in the treatment of the knee osteoarthritis . The autMore recently, a prospective trial started in 2020 has been started by Niewald et al. including 236 patients (64 knees and 172 hands) all with a diagnosis of osteoarthritis (OA). The aim of this study was to compare two schemes of treatment (3 Gy vs. 0.3 Gy). The study showed no statistically difference in pain control between the two schemes. Further studies need to be performed because there’s no evidence about the effect of low doses such as 0.3 Gy in the literature . Given the increasing interest in benign osteoarticular pathologies in recent years, Alvarez and colleagues have outlined a CT-based contouring atlas for non-malignant skeletal and soft tissue disorders . The aimOtt et al. in 2015 evaluated the long-term efficacy of two different RT schemes of 1 Gy/0.5 Gy over 3 weeks, twice per week used for 112 patients with diagnosis of achillodynia. The overall early (right at the end of RT), delayed (6 weeks after RT), and long-term (2 years after RT) response rates for all patients were 84 %, 88 %, and 95 %, respectively. This confirmed the positive role of RT for this kind of treatment . In 2021The role of RT on Heterotopic Ossification (HO) was supported by weak evidence. In 2014, a systematic review made by Ploumis et al. on a total of 27 studies of elbow HO showed that in most cases RT was stopped due to safety reasons. This review confirmed the lack of high-quality findings in the literature about RT in HO syndromes . Thanks Radiation therapy has been widely adopted in the treatment of various neurological disorders, for different aims such as pain relief, control of the symptoms, and obliteration of brain arteriovenous malformations. Moreover, RT is a non-invasive approach that can be safely adopted also in elderly patients. A summary of the collected evidence is reported in A total of 0.5% of the world’s population suffers from epilepsy. About 30–40% of the patients do not benefit from pharmacological therapy and are eligible for surgical treatment. In patients where the pharmacological and surgical alternatives have been exhausted, RT is an option. RT, compared to surgery, has the advantage of not being invasive with low risk of neurological damage to the patient. Rauch C. et al.  reportedLiang S et al.  reportedBarbaro et al.  evaluateOn these bases, radiotherapy has the potential to control the frequency and intensity of seizures in patients with pharmacoresistant epilepsy with mild long-term side effects if administered with proper fractionation, dose prescription, and target volume definition.Trigeminal neuralgia (TN) is a neurological disease that cause intense facial pain, usually paroxysmal and excruciating, due to an alteration of the V cranial nerve (predominantly the mandibular and maxillary branches). In patients with medications failure/significant adverse events, radiotherapy  may be an important therapeutic option. For SRS Gamma-Knife, linear accelerators and Cyber-Knife can be used. The three techniques showed no differences in terms of pain control, whereas the time to recurrence ranged from 6 to 48 months .3 was exposed at a dose of 10 Gy, with a maximum point dose (0.035 cm3) of 30% of the prescription dose. The pain relief rates were 87%, 82%, and 76% at 12, 24, and 36 months, respectively.Smith et al.  performeLovo EE et al.  reportedKundu B et al.  recentlyA retrospective study by Fraioli et al. of 45 patients compared SRS to FSRT using a linear accelerator. The authors compared 40 Gy in a single fraction and 72 Gy in six fractions. Patients treated with FSRT showed a higher pain recurrence rate than SRS (27.3% versus 8.3%) .Finally, reirradiation with SRS can still be used in case of recurrence, with a pain relief rate of 50% as showed in two retrospective studies ,81. The Brain arteriovenous malformations (AVMs) are the persistence of a direct link between an artery and a vein; the nidus is located where small arteries and veins are connected . Brain A3), lower Spetzler-Martin grade, higher dose, and steeper dose gradient. Embolization performed before SRS provided significantly lower obliteration rates than SRS alone  [3 and/or with high Spetzler-Martin grade [AVMs may be found as an incidental finding. They may be associated with intracranial hemorrhage, seizures, headaches, and/or neurological deficits. CT and MRI angiography are useful for the accurate diagnosis and nidus definition. Treatment approaches for AVMs are neurosurgery, embolization, and intracranial SRS. Stereotactic radiosurgery has a clinical obliteration rate of 60–80% ,70,71,720.00001) ,85. Some0.00001) . Fractio0.00001) . Most re0.00001) . SymptomGraves ophthalmopathy (GO) is the most frequent extrathyroidal manifestation of Graves’ disease. Although GO is severe in only 3–5% of affected individuals, quality of life is severely impaired even in patients with mild GO. RT is a well-established method of treatment for GO. The main rationale is its anti-inflammatory effect and the high radiosensitivity of T lymphocytes and orbital fibroblasts. Although there are several reports about the benefits of RT ,74,75, oOverall, favorable responses have been reported in 60% of cases. The best responses were noted for inflammatory signs and recent onset of extraocular muscle involvement. RT is well tolerated and safe and a careful selection of patients is necessary.All the above-mentioned disease can benefit from RT with interesting and promising results. At the same time, several pitfalls need to be managed before RT can be considered a safe and efficacious technique to manage non-oncological disorders.Specifically, more work is needed in the field of radiobiology to correctly quantify the RT damage to organs at risk, especially in the risk of secondary cancers ,92,93. AAt the same time, the number of prospective trials investigating the field of non-oncological RT is extremely poor and needs to be improved in the next years see .Most of the enrolling trials are investigating the new technique of Heart SBRT for arrhythmia disorders, whereas other diseases that can be managed with RT are not properly investigated. This aspect needs to be properly analyzed to test the role of modern RT in non-oncological fields and to sponsor the results among other specialists that do not know this approach. To this end, especially the scientific societies should undertake to study and spread the use of this type of RT, also involving specialists from other disciplines, following the path of DEGRO German Society.In this context, it is noteworthy that the spread use of hypofractionation RT schedules is involving several cancer diseases and will decrease the number of fractions of patients at the LINACs ,95,96 anScientific improvements of RT delivery, at the same time, needs to be tested in this particular field of disorders, as several other frontiers could be crossed in the next years that no-one can imagine now, such as the use of heart SBRT.To the best of our knowledge, the present paper is one of the most recent overviews on RT for non-malignant diseases. Notwithstanding the narrative nature of the review, our results may strongly support the need for further investigation and represent a starting point for future clinical research, also in the context of RT Scientific Societies.We finally recognize the limits of our review, in that it lacks explicit criteria for article selection and does not evaluate selected articles for validity.By setting up the ambitious goal of addressing all these challenges, non-oncological RT can become a clinical reality in the next years and a higher number of prospective trials can be designed and conducted in the near future, with the endorsement of RT Scientific Societies.


Sociodemographic, health and work-related questions were collected, and the Maslach Burnout Inventory and Resilience at Work Scale 20 instruments were applied. The data were submitted to descriptive analysis and to bivariate and partial correlations . work resilience presented an inverse correlation to emotional exhaustion  and depersonalization  and a direct one to professional achievement . The variable with the greatest influence on the correlation network was the perception of the impact of the pandemic on mental health. resilience interferes in the emotional exhaustion and low professional achievement domains of Burnout. Emotional exhaustion is conducted through minor psychological disorders, with an impact on the workers’ physical and mental health variables. The development of institutional resilience should be encouraged in order to moderate the illness. This can be characterized by difficulties in psychological, psychophysiological and behavioral adaptation which, mainly, affect professionals who perform their functions directly with people exposed to stressful situationsTo cope with adverse situations and experiences at work, the professionals often need to seek individual tools that prevent the high burden of stress and harms to health. Among these, work resilience involves aspects such as creativity and innovation, hope, authenticity, high self-esteem for problem solving, critical thinking, autonomy, ability to interact with the environment, being proactive, dealing with unpredictability, managing stress and the support from the family and friendsIt is noteworthy that there are several concepts of resilience in the literature, but without a universal definition. Its construct involves physics and engineering, psychology, social aspects and health, as well as organizational relationships-Inverse relationships between the Burnout syndrome and resilience have already been reported in the literature--A number of studiesIn view of the above, the following is asked: Which is the relationship between the Burnout dimensions and the work resilience of intensive care Nursing professionals in the COVID-19 pandemic? Therefore, this study aims at analyzing the relationship between the Burnout dimensions and the work resilience of intensive care Nursing professionals in the COVID-19 pandemic at four hospitals from southern Brazil.This is a cross-sectional and multicenter study, guided by the STROBE  guideline, used to report observational studiesSistema Único de Saúde, SUS); hospital H2 is a teaching hospital, a reference in trauma and had a specific wing for COVID-19; hospitals H3 and H4 are general and university hospitals. All hospitals were references in the care of patients with COVID-19, in need for intensive care.The study included four hospitals in the state of Rio Grande do Sul, Brazil, which were described as H1, H2, H3 and H4. Hospital H1 is a public and university institution, mostly providing care via the Unified Health System  and has the same number of non-redundant elements in the partial correlation matrix [(18*17/2)]All professionals were invited to the study. Non-probabilistic sampling was used. Sample calculation took into account the network analysis, which estimates the partial correlation between the variables and the number of variables included in the analysis. The sample size exceeds the number of variables in the model , health , work , minor psychological disorders (MPD)Consolidação das Leis do Trabalho, CLT), with formal registration; temporary, with a contract of defined duration and statutory, referring to public servants.The employment contract variable included employees, who respond to the rules established by the Consolidation of Labor Laws  to 5 (excellent). To assess the perception of the impact of the pandemic on physical health and mental health, a five-point Likert scale was used, varying from 1 (no impact) to 5 (intense impact).,To evaluate the Burnout syndrome, the Maslach Burnout Inventory (MBI), validated in Brazil, was usedhttp://www.workingwithresilience.com.au website.To assess work resilience, the Resilience at Work - RAW Scale Brazil 20 was used, developed in Australia,To track minor psychological disorders, the Self-Reporting Questionnaire (SRQ-20) was used, which contains 20 dichotomous questions about depressive, anxious and psychosomatic symptoms that occurred in the last 30 days from the answer. The score of one (1) indicates presence of symptoms and zero (0), absence. Seven or more affirmative answers are considered to identify minor psychological disordersThe workers were invited through the institutional email service, receiving the research instrument, via Google Forms and the Free and Informed Consent Form (FICF). The form received provided access to the FICF first. Subsequently, it was subdivided into sections: general worker’s data , information about work (labor issues), Maslach Burnout Inventory, Self-Reporting Questionnaire and the Resilience at Work Scale - 20, constituting 93 mandatory questions. Prior evaluation of the questionnaire was performed to identify possible failures and estimate the response time.As a strategy during data collection, visits were made to the units to invite the professionals who had not been granted access to the research instrument and also to remind them about the study.In view of the limitations related to the critical pandemic period, it was not possible to carry out supervision tasks during completion of the forms. However, all professionals were instructed to answer them.® spreadsheets and later transferred to the SPSS® Statistical Package for the Social Sciences, SPSS Inc, Chicago), version 18.0 for Windows, and to the JASP platform - Jeffreys’s Amazing Statistics Program (version 0.14.1)The data were stored in ExcelDistribution of the variables was verified using the Shapiro-Wilk test, considering p≤0.05 to indicate non-adherence to normal distribution. The parametric variables (age and time working in the profession) were described as mean and standard deviation. The other continuous, non-parametric variables were described in medians and interquartile intervals. The data obtained by means of the Likert scale were described in medians and interquartile ranges. The categorical variables were presented through of absolute and relative frequencies.To verify the correlation between the variables, bivariate Spearman correlations were performed, suitable for analyses that include ordinal and continuous variables. To evaluate the difference between two groups and the Burnout syndrome domains , the Mann-Whitney test was used and, for more than two groups, Kruskal-Wallis and Dunn. Therefore, it was verified which independent variables  presented a significant relationship (p<0.05) with at least one of the dependent variables.To investigate the relationship between Burnout and resilience at work, a network analysis was carried out, which comprises two stages: the first consists in estimating the matrix of regularized partial correlations  through of the Graphical Least Absolute Shrinkage and Selection Operator (GLASSO) algorithm and the second stage, in which the partial correlation matrix is represented in a two-dimensional plane in a graphic object(17). The partial correlations are estimated using the inverse matrix (m-1) of the bivariate correlation matrix, which, in the JASP software, are calculated using the “cor_auto” function that considers the measurement and distribution level of each pair of variables .The resulting non-directional network is formed by vertices, representing the variables investigated, and by edges, representing the partial correlations among them. The partial correlations can vary in magnitude (more or less thick lines) and in positive (blue) or negative (red) directionConselho Nacional de Saúde, CNS)The study was approved by the Research Ethics Committee for each institution under study, as well as by the National Research Ethics Commission , under opinion number 4,152,027 and CAAE: 33105820.2.0000.0008. The ethical precepts were respected according to Resolution 466/12 of the National Health Council . The mean age was 38.41 ± 7.42 years old and the median for children was 1 (0-2). Regarding marital status, 75.2% (n=115) were married or had a partner. The workers stated being white- , brown-  and black-skinned . The level of vocational/technical training represented 43.8% (n=67), followed by specialization/residency , master’s/PhD degree  and undergraduate degree . Regarding life habits, 30.1% (n=46) reported an increase in alcohol consumption during the pandemic and 92.2% (n=141) were non-smokers. Physical activity was reported by 26.8% (n=41) of the workers. In addition to that, the perception of sleep quality had a median of 3 (2-4).The work-related characteristics of intensive care Nursing professionals are presented in Regarding the workers’ psychological health, the prevalence of minor psychological disorders was 54.9% (n=84). In relation to Burnout, 11.1% (n=17) of the workers had the syndrome. Regarding the Burnout domains, 28.8% (n=44) presented emotional exhaustion; 39.9% (n=61), depersonalization and 26.1% (n=40), low professional achievement. Emotional exhaustion was low in 21.6% (n=33), moderate in 49.7% (n=76) and high in 28.8% (n=44). Depersonalization was low in 18.3% (n=28), moderate in 41.8% (n=64) and high in 39.9% (n=61). Regarding professional achievement, it was low in 24.2% (n=37), moderate in 49.7% (n=76) and high in 26.1% (n=40).The presence of minor psychological disorders was correlated with emotional exhaustion , depersonalization  and low professional achievement . Resilience at work was inversely correlated with emotional exhaustion  and depersonalization  and directly correlated with professional achievement . There was a negative correlation between resilience at work and minor psychological disorders . The network of correlations between the Burnout dimensions and resilience at work is represented in It is noted that depersonalization is driven by emotional exhaustion. Professional achievement directly interferes with resilience at work. Resilience at work proved to be a protective factor against emotional exhaustion.The socio-occupational variables, with a statistically significant difference with the Burnout dimensions and/or with resilience at work, were included in the network analysis.Emotional exhaustion was, significantly, related to time working in the institution (p=0.005), working time in the sector (p=0.009), perception of the impact of the pandemic on physical (p<0.001) and mental (p<0.001) health, days of work leaves (p=0.024), position (p=0.007), employment contract (p=0.01), perceived risk of exposure to COVID-19 (p<0.001), work shift (p=0.001) and sleep quality (p<0.001).Depersonalization was, significantly, related to the practice of regular physical activity (p=0.01), working time in the institution (p=0.043), the perception of the impact of the pandemic on physical (p=0.001) and mental (p=0.001) health, perceived risk of exposure to COVID-19 (p<0.001), sleep quality (p=0.02) and work shift (p=0.01).Professional achievement was, significantly, related to time working in the institution (p=0.005), the perception of the impact of the pandemic on mental health (p<0.001), days of work leaves (p=0.024), employment contract (p=0.009), need to distance from work (p=0.035) and work shift (p=0.001).Resilience at work was, significantly, related to the perception of the impact of the pandemic on mental health (p<0.001), employment contract (0.024), sleep quality (0.012) and work shift (p=0.001).Analyzing the network of partial correlations , some reResilience proved to be a protective factor against minor psychological disorders and emotional distress. Resilience also presented a strong positive correlation with professional achievement. The morning shift professionals presented an inverse correlation to resilience at work and to the position of nurse. The gender variable did not interfere with the network model. Centrality measures allow us to identify the most relevant variables on the network of regularized partial correlations, with the greatest potential to provide changes. Therefore, according to the centrality table , the varThe findings of this study evidenced resilience at work as a protective factor in the presence of high levels of emotional exhaustion and depersonalization, domains with the highest scores in the Burnout syndrome.-A number of studiesdelirium with a higher incidence should also be considered when measuring the workloadThe work environment of intensive care units is characterized by high technological density and complexity of care, requiring from the professional technical and specific knowledge, quick thinking, constant scientific updating and emotional balance to face adversities. During the COVID-19 pandemic, an Italian studyAll these factors, inherent to work in intensive care, reveal the profound changes and adaptations that have taken place in the services in the face of the pandemic, becoming stressors and potentially aggravating health. The perception of the impact of the pandemic on physical and mental health and the perception of exposure to the disease showed to interfere with mental health, in the presence of minor psychological disorders and high emotional exhaustion. A review study pointed out that the most frequent feeling among health workers during the pandemic was fear and that negative perceptions related to mental health were linked to insomnia, psychological distress, Burnout, anxiety and depressive symptoms. As for physical health, the manifestations were limited to symptoms resulting from COVID-19 infectionA qualitative studyThe perception of the impact of the pandemic on physical health was related to the need to distance from work and to longer periods of time away from work. In addition to leaves due to COVID-19, mental health issues such as somatization can be related to high stress levels, which are often only considered when they interfere with physical health to justify the need for a work leave. A study with the objective of performing a psychological intervention in health professionals evidenced that there is resistance on the part of many workers to accept psychological support. The authors point out that, despite showing excitability, irritability, unwillingness to rest and signs of psychological distress, the nurses refused any psychological help and stated that they had no problems. Among the staff, this refusal of psychological support was linked to a desire for uninterrupted rest, sufficient protective supplies, and the need for training in psychological skills to deal with the patients’ anxiety, panic and other emotional problems, as well as the support provided by the mental health team to these patientsTherefore, when the impact of work on health is not managed, it can lead to physical and psychological harms. In addition, the relationship between the presence of health problems and greater susceptibility to emotional exhaustion was also evidenced in a study carried out with Portuguese nurses during the pandemicIt is noteworthy that our data come from a critical period of the pandemic, at the peak of the number of cases, with overcrowding of intensive care units and in the absence of vaccines, which reflects in high exposure of the professionals. According to the Federal Nursing CouncilSleep quality and performance of physical activities showed a positive impact on physical health and a protective factor for minor psychological disorders. It is known that sleep has a function of physical restoration, conservation, energy and protectionA study carried out in China indicated that working on the front lines in the fight against the pandemic was, significantly, associated with increased anxiety and stress levels, with a negative influence on the professionals’ sleep qualityRegarding the practice of physical activities, a study showed a lower risk of illness for the group that exercised regularlyResilience at work proved to be a protective factor for the mental health variables, such as presence of minor psychological disorders, emotional exhaustion and depersonalization. A study carried out in China, with front-line nurses at the peak of the COVID-19 pandemic, revealed the association between resilience and Burnout in this population. Resilience showed significant negative correlations with burnout, emotional exhaustion, depersonalization and reduced personal achievement. Negative affects such as fear, nervousness, irritability, hostility and shame and positive affects such as enthusiasm, attention, pride, hope and contentment, were mediators in the Burnout domains, whose study proposes to establish resilience strategies for front-line health professionals to reduce burnoutA study conducted with front-line female nurses from Philippines also evidenced that increased levels of personal resilience, organizational support and social support in nurses were associated with reduced anxiety levels related to COVID-19Our findings evidenced a direct relationship between emotional exhaustion and longer time in the profession. In the literature, professional experience tends to improve sound awareness in problem solving, which can increase confidence in the professional actions, inducing less stress and anxiety,-As for work shift, the morning professionals presented an inverse relationship to resilience at work. According to the literature, professionals with low levels of resilience present a higher risk of illness and this is, mainly, related to night shift professionals. The factors related to the risk of illness mainly include sleep disorders, long working hours and agreement with the chronotype, in addition to the practice of physical activity as a protective factorIn relation to the professional position, a review study on resilience in health workers highlighted that Nursing professionals have lower resilience scores when compared to other professions, and that front-line professionals also have lower resilience rates. The authors report that the nurses with higher resilience scores had fewer negative mental health results, including anxiety, depression and post-traumatic stress disorderFurthermore, managers should prioritize building personal resilience among front-line nurses, as greater personal resilience was associated with less anxiety motivated by COVID-19. Positive coping strategies and nurses’ self-efficacy should be encouraged, in addition to providing adequate organizational support, which involves maintaining a safe work environment, availability of quality Personal Protective Equipment in sufficient numbers, supplies to prevent infections, provision of accurate and timely information about the disease and implementation of training sessions relevant to COVID-19As limitations, the cross-sectional design does not allow monitoring the individuals to verify the impacts of the pandemic on mental health, requiring a cohort study. There are also few investigations that assess resilience at work with the instrument used, creating difficulties in corroborating some results. In our study, only healthy workers were included, as well as an important percentage of new workers in the profession and in the institution, with attenuated risk factors for developing Burnout syndrome in the first moment of the pandemic, when data collection took place.This study has important implications about strategies that can be made available to Nursing professionals in coping with COVID-19 and any other possible pandemic. The network analysis allows for a more realistic assessment of the variables that affect workers’ health and that may be associated with resilience at work. In addition to that, the advancement of knowledge about resilience at work is highlighted, as the scale applied to the professionals is still recent and not widespread, with the potential to fill gaps in knowledge.Resilience positively interferes in the emotional exhaustion and low professional achievement domains of Burnout. Emotional exhaustion is conducted through minor psychological disorders, with an impact on the workers’ physical and mental health variables. The level of exposure to COVID-19 influences the perception of the impact of the pandemic on mental health. Strategies that work on the professionals’ resilience can guarantee more positive responses to adversities and should be considered at the institutional level to minimize the occurrence of Burnout among the intensive care Nursing team.