Circulating levels of IL-6 and TGF-ß1 in patients with prostate cancer undergoing radiotherapy: associations with acute radiotoxicity and fatigue symptoms.

BACKGROUND: The goal of research was to investigate the possible relations between serum concentrations of IL-6 and TGF-ß1, individual and clinical characteristics, and adverse effects of radiotherapy in patients with prostate cancer: acute and late genitourinary and gastrointestinal toxicity, and fatigue. METHODS: Thirty-nine patients with localized or locally advanced prostate cancer who were treated with radiotherapy were enrolled in this study. The acute radiotoxicity grades and fatigue levels were assessed during the radiotherapy and 1 month after the radiotherapy. Estimation of the late radiotoxicity was performed every three months in the first year, every four months in the second year, and then every six months. Serum levels of IL-6 and TGF-ß1 were determined before radiotherapy and after the 25th radiotherapy fraction by ELISA. RESULTS: The significant positive association between diabetes mellitus and changes in acute genitourinary toxicity grades during the radiotherapy was observed in prostate cancer patients. In addition, patients who were smokers had significantly higher maximum fatigue levels in comparison with patients who were non-smokers. The circulating IL-6 levels were significantly higher after the 25th radiotherapy fraction in comparison with levels determined before radiotherapy. The significant positive correlations between pretreatment TGF-ß1 levels and maximum genitourinary toxicity grades and between TGF-ß1 levels after the 25th fraction and genitourinary toxicity grades after the 25th fraction, were found. The pretreatment IL-6 concentrations and TGF-ß1 concentrations after the 25th fraction were positively correlated with maximum genitourinary toxicity grades. The IL-6 levels after the 25th fraction were positively associated with genitourinary toxicity grades after this fraction. The pretreatment IL-6 concentrations were significantly positively correlated with maximum fatigue scores. The significant positive correlation between IL-6 concentrations and fatigue scores after the 25th fraction was determined. The positive correlations between IL-6 and TGF-ß1 concentrations measured after the 25th fraction and maximum fatigue scores were observed. CONCLUSIONS: Our results suggest that serum levels of IL-6 and TGF-ß1 might influence the severity of acute genitourinary radiotoxicity and fatigue in patients with prostate cancer. Combining clinical parameters and circulating cytokine levels might be useful for the prediction of adverse reactions to radiotherapy.

Severe hematologic temozolomide-related toxicity and lifethreatening infections.

Glioblastoma is the most frequent primary malignant brain tumor in adults. With the number of symptoms and signs, it belongs to diseases where a lot of treatment modalities are often applied. A standard treatment for patients with glioblastoma includes surgical resection followed by radiotherapy with concomitant and adjuvant temozolomide. Each type of treatment has its own toxicity. Temozolomide is an oral alkylating cytotoxic drug and like any other alkylating agent can induce side effects. Although temozolomide is generally a well tolerated drug, with rare severe toxic effects, sometimes certain toxicities can overcome the life risk of the underlying malignancy. By reviewing the literature, we have selected the cases with severe clinical presentation where some of them had a lethal outcome and we have chosen to present them in this article. In some patients with noticeable hematological toxic effects, as well as those with serious infections, attention must be paid to their treatment, as toxic effects can deepen and develop new toxicity, which all lead to a vicious circle without a favorable outcome. Preventive use of antiviral drugs should be considered before the treatment with temozolomide in patients with a positive history of viral infections such as Hepatitis B infection. In order to prevent rare but possible opportunistic infections, it is necessary to familiarize the patients with the treatment, toxicity and rare opportunistic infections. These infections can be triggered by various factors from the nearest environment, including both domestic and wild animals and pets.

What did COVID-19 pandemics teach us about single-fraction radiotherapy for painful bone metastases-State of the art or undertreatment?

BACKGROUND: Choosing the optimal treatment approach for patients with painful bone metastases during the COVID-19 pandemic became challenging. A simple technique, single fraction radiotherapy was recommended for these patients usually referring to bone metastases as a single entity, although it is a very heterogeneous group of patients. AIM: This study aimed to analyze the response to palliative single fraction radiotherapy in relation to age, performance status, primary tumor, histopathology, and bone localization in the group of patients with painful bone metastases. METHODS: A clinical, prospective, non-randomized study was conducted at the Institute for Oncology and Radiology of Serbia, which included 64 patients with noncomplicated, painful bone metastases who underwent palliative, pain-relieving radiation therapy with a single tumor dose of 8Gy in a single hospital visit. Response to treatment was patient reported via telephone interview using visual analog scale. The response assessment was based on the international consensus panel of radiation oncologists. RESULTS: In the entire group of patients, 83% responded to radiotherapy. No statistically significant difference was observed in response to therapy, time to reach the maximum response, degree of pain reduction, nor in response duration depending on the patient's age, performance status, the primary origin of the tumor, histopathology, or location of the metastasis (bone) that was irradiated. CONCLUSION: Regardless of clinical parameters, palliative radiotherapy with a single dose of 8Gy can be considered very effective in quick pain relief in patients with noncomplicated painful bone metastases. Single fraction radiotherapy in a single hospital visit, as well as patient-reported outcome for these patients may be considered favorable beyond Covid pandemics.

Factors associated with preoperative and early and late postoperative seizures in patients with supratentorial meningiomas.

OBJECTIVE: Risk factors for epilepsy in meningioma patients are not yet clearly defined, however, seizure freedom is a significant factor for quality of life after surgery. METHODS: We performed a retrospective study of the 333 adult patients who received surgery for supratentorial meningioma at our center. Various clinical, radiological, and surgical variables were included in the multivariate regression, and the outcomes measured were the occurrence of seizure(s) preoperatively, during the hospitalization, and during the follow-up period. RESULTS: A total of 89 (26.7%) patients experienced preoperative seizures, of whom 62.9% were seizure free after the surgery. Of 244 patients without epilepsy before surgery, 11.9% had at least one seizure postoperatively. In total, 63 of our patients (18.9%) experienced seizures after the surgery, of whom 20 had refractory epilepsy. Multivariate analysis identified the following predictors of preoperative seizures: the absence of headache (OR: 0.23, CI: 2.55-8.50), the presence of significant peritumoral edema (OR: 4.35, CI: 2.57-7.35), and younger age (OR: 0.97 per year increase, CI: 0.95-0.99). Factors associated with early postoperative seizures were: younger age (OR: 0.96 per year increase, CI: 0.93-0.99) and the presence of preoperative seizures (OR: 2.73, CI: 1.13-6.57), while the presence of preoperative seizures (OR: 4.73, CI: 2.05-10.92), tumor progression (OR: 5.38, CI: 2.25-12.89), and neurological worsening (OR: 5.21 CI: 1.72-15.81) were significant for late postoperative seizures. SIGNIFICANCE: Our results from a single-center meningioma cohort confirm, in general, data from some previous studies regarding patients' characteristics for both preoperative and overall postoperative epilepsy. Besides previously described risk factors, younger age was important for preoperative and early postoperative seizures. Epilepsy is common in patients with recurrence of meningioma, but the variables of significance for refractory seizures in these patients require further examination.

Transitioning from face-to-face to distance education. Part 1: A cross-sectional study in the former Yugoslavia during COVID-19.

BACKGROUND: The countries of the former Yugoslavia have health and education systems with the same tradition but these have changed over the years. Little is known about how family medicine teaching transitioned from face-to-face to distance education during the COVID-19 pandemic. OBJECTIVES: to investigate student/teacher experience in transitioning from face-to-face to distance education. METHODS: A cross-sectional, online survey was conducted among 21 medical schools of the former Yugoslavia between December 2021 and March 2022. Under/postgraduate teachers and students who taught/studied family medicine during the academic year 2020/2021 were invited to participate. Of 31 questions for students and 35 for teachers, all but nine open questions were analysed using descriptive statistics. RESULTS: Seventeen of 21 medical schools contributed data involving 117 participants representing all countries of the former Yugoslavia. At the beginning of the pandemic, 30%, 26% and 15% of teachers, students and trainees, respectively, received formal preparation in distance education. Of these, 92% of teachers and 58% of students/trainees felt they were not adequately prepared. Synchronous teaching was the main method used, with a third using hybrid methods. All participants were least confident about online assessment. More than 75% of respondents agreed that lectures could be kept online, not patient consultations or practical skills' classes. CONCLUSION: Teachers used various old and new methods to provide learning opportunities despite COVID-19 constraints. Effective technology-based strategies are essential to ensure assessment integrity and enhance the learning environment.

Despite limited preparedness, teachers and students/trainees transitioned to distance education.Students/trainees believed synchronous delivery of lectures and small group work can be conducted online but not practical skills' classes.Online assessments and practical work with patients were considered the most challenging aspects of distance education.

Transitioning from face-to-face to distance education. Part 2: A qualitative study in the former Yugoslavia during COVID-19.

BACKGROUND: Similar to other countries, Departments of Family Medicine in the former Yugoslavia had to transition from face-to-face to distance education during COVID-19. OBJECTIVES: To elucidate obstacles and facilitators of the transition from face-to-face to distance education. METHODS: A cross-sectional, multicentre, qualitative study design was used to analyse nine open-ended questions from an online survey using inductive thematic analysis. The questionnaire was distributed to 21 medical schools, inviting them to involve at least two teachers/students/trainees. Data were collected between December 2021 and March 2022. RESULTS: In 17 medical schools, 23 students, 54 trainees and 40 teachers participated. The following themes were identified: facilitators and barriers of transition, innovations for enhancing distance education, convenience of distance education, classical teaching for better communication, the future of distance education, reaching learning outcomes and experience of online assessment. Innovations referred mainly to new online technologies for interactive education and communication. Distance education allowed for greater flexibility in scheduling and self-directed learning; however, participants felt that classical education allowed better communication and practical learning. Teachers believed knowledge-related learning outcomes could be achieved through distance education but not teaching clinical skills. Participants anticipated a future where a combination of teaching methods is used. CONCLUSION: The transition to distance education was made possible thanks to its flexible scheduling, innovative tools and possibility of self-directed learning. However, face-to-face education was considered preferable for fostering interpersonal relations and teaching clinical skills. Educators should strive to strike a balance between innovative approaches and the preservation of personal experiences.

Participants found that distance education offers many possibilities, mainly self-directed, flexible learning.Participants felt that face-to-face education remains invaluable since it facilitates communication and the development of practical skills.A balance between new technologies and personal encounters was believed to be best.

Association between microRNAs 10b/21/34a and acute toxicity in glioblastoma patients treated with radiotherapy and temozolomide.

A personalized approach to chemoradiation is important in reducing its potential side effects and identifying a group of patients prone to toxicity. MicroRNAs have been shown to have a predictive potential for radiotoxicity. The goal of the study was to test if levels of miRNA in peripheral blood mononuclear cells of glioblastoma patients are associated with toxicity and to identify the peak time point for toxicity. MicroRNA-10b/21/34a levels were measured in 43 patients with and without toxicity, at baseline, at the 15th, and at the 30th fraction by Real-Time quantitative Polymerase Chain Reaction. MicroRNA-10b/21 levels increased with toxicity grade (p = 0.014; p = 0.013); miR-21/34a levels were significantly different between patients with and without toxicity at the 15th fraction (p = 0.030; p = 0.045), while miR-34a levels significantly changed during treatment (p < 0.001). All three miRNAs showed a significantly high positive correlation with one another. MiR-34a might be considered as a predictive factor for toxicity due to its changes during treatment, and differences between the groups with and without toxicity; miR-10b might be used to predict toxicity; miR-10b/21 might be used for predicting the grade of toxicity in GB patients.

Clinical analysis of COVID-19 positive cancer inpatients in National Cancer Center in Serbia.

INTRODUCTION: The outbreak of COVID-19 has had an impact on global healthcare as well as on radiotherapy practice in many countries. This study aimed to identify clinical characteristics of Coronavirus Disease 2019 (COVID-19) infected cancer inpatients, as well as what impact this infection had on radiation treatment of the patients. METHODOLOGY: In this retrospective study, we included cancer inpatients with laboratory confirmed COVID-19 infection during the radiotherapy or chemoradiation in April 2020 in National Cancer Research Center in Serbia. Data were obtained from the medical records between 1 April and 1 July 2020. RESULTS: A total of 49 COVID-19 infected cancer inpatients were included. The most frequently reported cancers were head and neck cancers, in twenty-three patients (46.8%). Lymphopenia was present in 77.5% of the patients. Red blood cells, haemoglobin and platelets were significantly lower during incubation or diagnosis of COVID-19. Twenty-seven (55.1%) patients did not finish radiotherapy. The age of patients who finished radiotherapy after COVID-19 infection was significantly lower compared to the patients who did not finish radiotherapy (60.5 ± 7.8 vs. 68.6 ± 11.2; p < 0.005). CONCLUSIONS: COVID-19 infected cancer patients in radiotherapy practice show similar symptoms and demographic characteristics as the general population infected with SARS-CoV-2 virus. Patients with head and neck cancers may be susceptible to infection with COVID-19. Old age and male gender may be risk factors for discontinuation of radiotherapy in COVID-19 infected cancer patients.

Long-lasting Thrombocytopenia after Transient Pancytopenia Induced by Short-Term Concomitant Radiotherapy and Temozolomide.

We describe long-lasting and incompletely resolved thrombocytopenia after transient profound pancytopenia in a 62-year-old female patient with glioblastoma after short-term radiotherapy with temozolomide. Pancytopenia was present for more than 4 weeks and thrombocytopenia for more than 6 months, without platelet recovery to normal levels. LEARNING POINTS: Some patients may experience severe haematological manifestations after even short-term radiotherapy with temozolomide.In everyday practice, clinical models precisely predicting the haematological toxicity of concomitant treatment with temozolomide and radiotherapy is necessary, especially in countries where genetic tests are not available.Incomplete recovery of the cells of a particular bloodline over a long period may necessitate permanent discontinuation of chemotherapy or radiotherapy.

Comparative Analysis of Family Medicine Education and Exams at Cathedras of Family Medicine of Universities in Southeastern Europe - "Splitska inicijativa", Sarajevo, 2017.

Education means: learning, teaching or the process of acquiring skills or behavior modification through various exercises. Traditionally, medical education meant the oral, practical and more passive transferring of knowledge and skills from the educators to students and health professionals. Today the importance of focus on educational quality, particularly in the professions operating in the services required by people is agreed by all involved. The higher educational system shoulders some critical responsibilities in the economic, social, cultural and educational development and growth in the communities. In countries that are in transition it is in charge of educating professional human workforce in every field and if the education is optimal in terms of quality, it is capable of carrying out its responsibilities. It is reason why there is the necessity behind discovering some strategies to uplift the quality of education, especially at university level.. By increasing the courses and establishing universities and higher education centers, the countries around the world have generated more opportunities for learning, especially using modern information technologies. Regarding to evaluating different educational services quality, one of the most important measures should be the way to develop programs to promote quality and also due to the shortage of resources, evaluating the services quality enables the management to allocate the limited financial resources for realization whole educational process. Advances in medicine in recent decades are in significant correlation with the advances in the new models and concepts of medical education supported by information technologies. Modern information technologies have enabled faster, more reliable and comprehensive data collection. These technologies have started to create a large number of irrelevant information, which represents a limiting factor and a real growing gap, between the medical knowledge on one hand, and the ability of students and physicians to follow its growth on the other. Furthermore, in our environment, the term technology is generally reserved for its technical component. This terminology essentially means not only the purchase of the computer and related equipment, but also the technological foresight and technological progress, which are defined as specific combination of fundamental scientific, research and development work that gives a concrete result. The quality of the teaching-learning process at the universities in former Yugoslav countries and abroad, depends mainly of infrastructure that includes an optimal teaching space, personnel and equipment, in accordance with existing standards and norms at the cantonal or entity level, which are required to implement adequately the educational curriculum for students from first to sixth year by Bologna studying concept. For all of this it is necessary to ensure adequate funding. Technologies (medical and information, including communications) have a special role and value in ensuring the quality of medical education at universities and their organizational units (faculties). "Splitska inicijativa" project, which started 6 years ago as simple intention to exchange experiences of application new model of education, based on: Bologna studying concept, and other types of under and postgraduate education, was good idea to improve also theory and practice of it within Family medicine as academic and scientific discipline. This year scope of our scientific meeting held in Sarajevo on 24th and 25th March 2017, was quality assessment of theoretical and practical education and, also, evaluation of knowledge by students exams (a-y).