Chromosomal radiosensitivity in oncological and non-oncological patients with rheumatoid arthritis and connective tissue diseases.

BACKGROUND: The risk of developing late radiotoxicity after radiotherapy in patients with high chromosomal radiosensitivity after radiotherapy could potentially be higher compared to the risk in patients with average radiosensitivity. In case of extremely high radiosensitivity, dose reduction may be appropriate. Some rheumatic diseases (RhD), including connective tissue diseases (CTDs) appear to be associated with higher radiosensitivity. The question arises as to whether patients with rheumatoid arthritis (RA) also generally have a higher radiosensitivity and whether certain parameters could indicate clues to high radiosensitivity in RA patients which would then need to be further assessed before radiotherapy. METHODS: Radiosensitivity was determined in 136 oncological patients with RhD, 44 of whom were RA patients, and additionally in 34 non-oncological RA patients by three-colour fluorescence in situ hybridization (FiSH), in which lymphocyte chromosomes isolated from peripheral blood are analysed for their chromosomal aberrations of an unirradiated and an with 2 Gy irradiated blood sample. The chromosomal radiosensitivity was determined by the average number of breaks per metaphase. In addition, correlations between certain RA- or RhD-relevant disease parameters or clinical features such as the disease activity score 28 and radiosensitivity were assessed. RESULTS: Some oncological patients with RhD, especially those with connective tissue diseases have significantly higher radiosensitivity compared with oncology patients without RhD. In contrast, the mean radiosensitivity of the oncological patients with RA and other RhD and the non-oncological RA did not differ. 14 of the 44 examined oncological RA-patients (31.8%) had a high radiosensitivity which is defined as ≥ 0.5 breaks per metaphase. No correlation of laboratory parameters with radiosensitivity could be established. CONCLUSIONS: It would be recommended to perform radiosensitivity testing in patients with connective tissue diseases in general. We did not find a higher radiosensitivity in RA patients. In the group of RA patients with an oncological disease, a higher percentage of patients showed higher radiosensitivity, although the average radiosensitivity was not high.

Happiness Behind the Scenes: Associations between Heuristic Happiness and Related Dimensions in Skin Diseases.

Positive health approaches, such as happiness, are largely unexplored in medicine, including dermatology. Taking into consideration the various happiness measures, the aims of this cross-sectional study were to assess this concept using a 1-item heuristic happiness question and its related dimensions (Satisfaction with Life, Positive and Negative Affect, Quality of Life, and Compound Psychological Capital) in outpatients with different skin diseases between December 2019 and June 2020, and to examine the link between these dimensions. Overall, 414 dermatological patients were included: 67 with psoriasis, 84 atopic eczema, 10 mastocytosis, 19 nummular eczema, 84 malignant melanoma and 150 keratinocyte carcinoma. Comparing the skin diseases, differences were observed for heuristic happiness, Positive Affect, and some domains of Quality of Life and Compound Psychological Capital. Analysing the relationship between heuristic happiness and other happiness measures, the data revealed moderate to strong correlations (r = 0.30-0.46, p< 0.001) and variations in the understanding of happiness between the skin diseases. Overall, the most important facet of happiness was Hope as a domain of Compound Psychological Capital. This study emphasizes the individual definition of heuristic happiness in patients with skin diseases. A 1-item heuristic approach may be a simple and practical method to assess the complexity and individuality of happiness.

Kinase inhibitors increase individual radiation sensitivity in normal cells of cancer patients.

PURPOSE: Kinase inhibitors (KI) are known to increase radiosensitivity, which can lead to increased risk of side effects. Data about interactions of commonly used KI with ionizing radiation on healthy tissue are rare. PATIENTS AND METHODS: Freshly drawn blood samples were analyzed using three-color FISH (fluorescence in situ hybridization) to measure individual radiosensitivity via chromosomal aberrations after irradiation (2 Gy). Thresholds of 0.5 and 0.6 breaks/metaphase (B/M) indicate moderate or clearly increased radiosensitivity. RESULTS: The cohorts consisted of healthy individuals (NEG, n = 219), radiosensitive patients (POS, n = 24), cancer patients (n = 452) and cancer patients during KI therapy (n = 49). In healthy individuals radiosensitivity (≥ 0.6 B/M) was clearly increased in 5% of all cases, while in the radiosensitive cohort 79% were elevated. KI therapy increased the rate of sensitive patients (≥ 0.6 B/M) to 35% significantly compared to 19% in cancer patients without KI (p = 0.014). Increased radiosensitivity of peripheral blood mononuclear cells (PBMCs) among patients occurred in six of seven KI subgroups. The mean B/M values significantly increased during KI therapy (0.47 ± 0.20 B/M without compared to 0.50 ± 0.19 B/M with KI, p = 0.047). CONCLUSIONS: Kinase inhibitors can intensify individual radiosensitivity of PBMCs distinctly in 85% of tested drugs.

Kenntnisse bayerischer Schüler zu sexuell übertragbaren Infektionen: eine Querschnittsstudie.

HINTERGRUND UND ZIELE: Trotz zahlreicher Informationsquellen und Kampagnen zu sexuell übertragbaren Infektionen (STI) haben diese Krankheiten in Deutschland in den letzten Jahren zugenommen. Ziel war es, das Bewusstsein und den Wissensstand junger Schüler in Bayern zu sexuell übertragbaren Krankheiten (STI) mit Schwerpunkt auf humane Papillomaviren (HPV) zu bewerten. METHODEN: In einer vollständig irreversibel anonymisierten Querschnittsstudie wurden insgesamt 4100 bayerische Schüler im Alter zwischen 12 und 17 Jahren anhand eines Multiple-Choice-Fragebogens hierzu befragt. ERGEBNISSE: Insgesamt wurden 3834 Fragebögen in die Datenanalyse einbezogen. Interessanterweise ist der Bekanntheitsgrad von HPV im Vergleich zu anderen STI bemerkenswert geringer. Mädchen und Jugendliche, die bereits vorbeugende Jugendgesundheitsuntersuchungen absolviert hatten, zeigten im Durchschnitt ein größeres Wissen über STI. Darüber hinaus konnten wir zeigen, dass Jugendliche mit geringerem Bildungsniveau, wie Realschüler, über die geringsten Kenntnisse verfügten. SCHLUSSFOLGERUNGEN: Die Querschnittsstudie zeigt, dass viele junge Menschen noch unzureichend über STI informiert sind. Die Informationslücken unterstreichen die Notwendigkeit einer intensiven und langfristigen Aufklärungsarbeit.

Evaluation of the knowledge of students concerning sexually transmitted infections in Bavaria/Germany (a cross-sectional study).

BACKGROUND AND OBJECTIVES: Despite numerous information sources and campaigns on sexually transmitted infections (STIs), there has been an increase in STIs in Germany in recent years. The aim was to evaluate the awareness and knowledge level among young students in Bavaria/Germany for STIs with a focus on human papilloma viruses (HPV). METHODS: In a cross-sectional survey rendered completely and irreversibly anonymous, a total of 4,100 students from Bavaria between the ages of 12 and 17 were interviewed using a multiple choice questionnaire about their knowledge and awareness of STI, on the basis of gender, school education and preventive youth health examinations that had taken place. RESULTS: A total of 3,834 questionnaires were included in the data analysis. Interestingly, the awareness level for HPV is remarkably lower compared to other STIs. Girls and adolescents who had already taken preventive youth health examinations showed a higher knowledge of STIs on average. Additionally, we could show that adolescents of lower educational levels, such as secondary school students, had the least knowledge. CONCLUSIONS: The cross-sectional study shows that many young people are still insufficiently informed about STIs. The gaps in information and lack of knowledge underline the necessity of intensive and long-term educational work.

Molecular diagnostics in dermatology: An online survey to study usage, obstacles and requirements in Germany.

BACKGROUND AND OBJECTIVES: Molecular diagnostics (MDx) increasingly gains importance in dermatology and its application is a prerequisite for personalized medicine. The goal of this cross-sectional study was to determine how MDx is implemented in dermatologists' offices in the three fields of oncology, inflammation and infectiology and which hurdles office-based dermatologists face in terms of MDx. METHODS: Physician members of the Association of the German Dermatologists (Berufsverband der Deutschen Dermatologen e. V.; BVDD) were surveyed via an online questionnaire on MDx. RESULTS: 39.6 % of the 192 participants reported using MDx. Of these, the vast majority used MDx for diagnosing infectious diseases (86.5 % and 44.3 % of users perform MDx for detection of funghi and sexually transmitted diseases, respectively). Only a small minority applied MDx to answer oncological or immunological questions. The major obstacles for non-users as compared to users were difficulties in implementation, lack of expertise as well as time, personnel, and technical availability. Reimbursement was a main issue in both groups. CONCLUSIONS: Despite availability of specific therapies requiring precision medicine, MDx has not yet been broadly implemented in office-based dermatology. To advance MDx, more needs to be done in terms of continuous education, availability of reliable and valid tests, and reimbursability.

Influence of Gender on Radiosensitivity during Radiochemotherapy of Advanced Rectal Cancer.

Gender is increasingly recognized as an important factor in medicine, although it has long been neglected in medical research in many areas. We have studied the influence of gender in advanced rectal cancer with a special focus on radiosensitivity. For this purpose, we studied a cohort of 495 men (84.1% ≥ T3, 63.6% N1, 17.6%, M1) and 215 women (84.2% ≥ T3, 56.7% N1, 22.8%, M1) who all suffered from advanced rectal cancer and were treated with radiochemotherapy. The energy deposited, DNA double-strand break (dsb) repair, occurrence of chromosomal aberrations, duration of therapy, tumor regression and tumor-infiltrating lymphocytes, laboratory parameters, quality of life and survival were assessed. The residual DNA dsb damage 24 h after irradiation in lymphocytes was identical in both sexes. Furthermore, chromosomal aberrations accurately reflecting radiosensitivity, were similar in both sexes. There were no gender-dependent differences in tumor regression, tumor-infiltrating lymphocytes and outcome indicating no differences in the radiosensitivity of cancer cells. The irradiated tumor volume in women was slightly lower than in men, related to body weight, no difference was observed. However, when the total energy deposited was calculated and related to the body weight, women were exposed to higher amounts of ionizing radiation. During radiochemotherapy, decreases in blood lymphocyte counts and albumin and several quality-of-life parameters such as nausea and vomiting, loss of appetite, and diarrhea were significantly worse in women. There is no difference in radiation sensitivity between men and women in both normal tissue and tumors. During radiochemotherapy, the quality of life deteriorates more in women than in men. However, women also recover quickly and there are no long-term differences in quality of life.

Always Online? Internet Addiction and Social Impairment in Psoriasis across Germany.

With the World Health Organization (WHO) demanding further investigation of the social impairment and psychosocial burden of psoriasis, a first study identified a high prevalence of Internet addiction. The aim of this study was to assess social impairment and estimate the occurrence of Internet addiction along with depression, cigarette smoking, and alcohol dependency in individuals with psoriasis recruited online in a people-centered care approach. A cross-sectional online survey was carried out across Germany between March 2019 and June 2019. The questionnaire contained information on social impairment, smoking habits, as well as validated questionnaires on Internet addiction, depression, and alcohol dependency. Overall, 460 individuals (62.4% female; mean age: 45.9 ± 13.7 years) with psoriasis were included. Of those, 406 (88.3%) stated to be at least rarely socially impaired. The positive screening rate for Internet addiction was 8.5%. Furthermore, 40.0% had positive screenings for depression, 17.1% for alcohol dependency, and 32.6% for daily smoking. Positive screenings for Internet addiction and alcohol dependency were substantially more frequent in individuals with psoriasis than in the German general population. In order to meet the demands of the WHO, Internet addiction could be considered as a potential comorbidity in psoriasis and a focus on people-centered care is advisable for further research.

[Effects of an unconventional skin cancer prevention campaign : Impacts on the sun protection behavior of outdoor workers]. / Effekte einer unkonventionellen Hautkrebs-Präventionskampagne : Auswirkungen auf das Sonnenschutzverhalten von Außenberufstätigen.

BACKGROUND: The disease burden of actinic keratoses and keratinocyte carcinoma can be reduced by primary and secondary prevention. However, these measures are often poorly received, especially among the high-risk group of outdoor workers. OBJECTIVES: The aim of this follow-up study was to investigate whether an improvement in sun protection and awareness of skin changes could be observed among the study population, especially outdoor workers, one year after a prevention campaign focusing on this topic. MATERIALS AND METHODS: In 2017, all participants who initially participated in a study at the Bavarian Central Agricultural Festival 2016 and agreed to participate in the follow-up study were contacted by mail and received the same questionnaire and evaluation questions regarding possible behavioral changes. RESULTS: A total of 400 people took part in the follow-up study (response rate 52.8%). Of the 240 outdoor workers, 45.0% said they were more conscious of protecting themselves from the sun and 68.8% said they were more aware of skin changes. About 85.0% of outdoor workers indicated that they would consult a dermatologist earlier and 65.8% desired further prevention campaigns regarding skin cancer and sun protection. CONCLUSION: Overall, the majority of participants reported that they had improved sun protection behavior and awareness of skin changes after the intervention. Based on the participants' self-disclosure, especially outdoor workers tended to use sun protection measure more frequently. These findings underline the importance of target group-oriented awareness and prevention campaigns to reduce the burden of skin cancer.

Is in vivo and ex vivo irradiation equally reliable for individual Radiosensitivity testing by three colour fluorescence in situ hybridization?

BACKGROUND: Individual radiosensitivity is influencing the outcome of radiation therapy. A general ex vivo testing is very work-intensive. It is of interest to see if a significant prediction concerning the sensitivity can be made by in vivo irradiation during radiation treatment. METHODS: Blood samples of 274 patients with rectal cancer and 43 lung cancer patients receiving radiotherapy were examined after 2 Gy ex vivo and in vivo ionizing radiation. Chromosomes # 1, 2 and 4 were stained by the 3-color-fluorescence in situ hybridization. Chromosomal aberrations were analyzed as breaks per metaphase (B/M). The deposited energy per session was calculated for each patient. RESULTS: Weak correlation could be found between the chromosomal aberrations ex and in vivo. Though receiving significantly smaller deposited energy during radiation therapy (RT) the lung cancer cohort displayed B/M values similar to the rectal cancer cohort. Considering the individual deposit energy differences improved slightly the correlation. CONCLUSIONS: As various factors influence the induction of chromosomal aberrations it seems not feasible to estimate individual radiosensitivity via in vivo irradiation. An ex vivo estimation of individual radiosensitivity should be preferred.

Rate of individuals with clearly increased radiosensitivity rise with age both in healthy individuals and in cancer patients.

BACKGROUND: The question of an age dependence of individual radiosensitivity has only marginally been studied so far. Therefore, we analyzed blood samples of healthy individuals and cancer patients of different ages to determine individual radiosensitivity. METHODS: Ex vivo irradiated blood samples of 595 individuals were tested. Chromosomes 1, 2 and 4 were stained by 3-color fluorescence in situ hybridization and aberrations were analyzed. Radiosensitivity was determined by the mean breaks per metaphase (B/M). RESULTS: Healthy individuals (mean age 50.7 years) had an average B/M value of 0.42 ± 0.104 and an increase of 0.0014B/M per year. The patients (mean age 60.4 years) had an average B/M value of 0.44 ± 0.150 and radiosensitivity did not change with age. In previous studies we found that from a value of 0.6B/M on an individual is considered to be distinctly radiosensitive. The portion of radiosensitive individuals (B/M > 0.6) increased in both cohorts with age. CONCLUSION: Individual radiosensitivity rises continuously with age, yet with strong interindividual variation. No age related increase of radiosensitivity can be demonstrated in patients due to the strong interindividual variation. However among old cancer patients there is a higher probability to have patients with clearly increased radiosensitivity than at younger age.

What Do Germans Want to Know About Skin Cancer? A Nationwide Google Search Analysis From 2013 to 2017.

BACKGROUND: Experts worldwide agree that skin cancer is a global health issue, but only a few studies have reported on world populations' interest in skin cancer. Internet search data can reflect the interest of a population in different topics and thereby identify what the population wants to know. OBJECTIVE: Our aim was to assess the interest of the German population in nonmelanoma skin cancer and melanoma. METHODS: Google AdWords Keyword Planner was used to identify search terms related to nonmelanoma skin cancer and melanoma in Germany from November 2013 to October 2017. The identified search terms were assessed descriptively using SPSS version 24.0. In addition, the search terms were qualitatively categorized. RESULTS: A total of 646 skin cancer-related search terms were identified with 19,849,230 Google searches in the period under review. The search terms with the highest search volume were "skin cancer" (n=2,388,500, 12.03%), "white skin cancer" (n=2,056,900, 10.36%), "basalioma" (n=907,000, 4.57%), and "melanoma" (n=717,800, 3.62%). The most searched localizations of nonmelanoma skin cancer were "nose" (n=93,370, 38.99%) and "face" (n=53,270, 22.24%), and the most searched of melanoma were "nails" (n=46,270, 70.61%) and "eye" (n=10,480, 15.99%). The skin cancer‒related category with the highest search volume was "forms of skin cancer" (n=10,162,540, 23.28%) followed by "skin alterations" (n=4,962,020, 11.36%). CONCLUSIONS: Our study provides insight into terms and fields of interest related to skin cancer relevant to the German population. Furthermore, temporal trends and courses are shown. This information could aid in the development and implementation of effective and sustainable awareness campaigns by developing information sources targeted to the population's broad interest or by implementing new Internet campaigns.

Idelalisib may have the potential to increase radiotherapy side effects.

INTRODUCTION: Idelalisib is approved for the treatment of relapsed chronic lymphocytic leukemia together with Rituximab and for monotherapy of follicular B-cell non-Hodgkin's lymphoma and small lymphocytic lymphoma. It is a potent and selective phosphatidylinositol 3-kinase-δ (PI3K-δ) inhibitor. PI3K-δ primarily is expressed in B-cells and prevents effectively proliferation in malignant B-cells. METHODS: We provide a detailed report on treatment history and photo documentation of acute adverse effects of radiation therapy with simultaneous Idelalisib medication in one case of B-CLL. Radiosensitivity tests were performed for the index patient under Idelalisib and after the addition of Idelalisib to healthy individuals' blood. Radiosensitivity in human lymphocytes was analyzed with a three color in situ hybridization assay. Primary skin fibroblasts were studied after a treatment with Idelalisib for apoptosis, necrosis and cell cycle using flow cytometry. DNA double-strand break repair was analyzed by γH2AX immunostaining. RESULTS: The index patient presented a strong grade 2 radiodermatitis and grade 3 mucositis after irradiation with 20 Gy and a simultaneous intake of Idelalisib. Irradiations without Idelalisib medication were well tolerated and resulted in not more than grade 1 radiodermatitis. The index patient under Idelalisib had a radiosensitivity of 0.62 B/M which is in the range of clearly radiosensitive patients. A combined treatment of lymphocytes with 2 Gy and 10 nmol/l Idelalisib showed a tendency to an increased radiosensitivity. We found a clear increase of apoptosis as a result of the combined treatment in the Idelalisib dose range of 1 to 100 nmol/l compared to solely irradiated cells or solely Idelalisib treated cells (p = 0.05). CONCLUSION: A combined Idelalisib radiotherapy treatment has an increased risk of side effects. However, combined therapy seems to be feasible when patients are monitored closely.