LEPTIN: FROM APPETITE SUPPRESSION TO AUTOIMMUNITY

The hormone leptin is released by adipocytes accordingly to current energy stores to suppress appetite. Apart from this, leptin acts as a proinflammatory cytokine and strongly stimulates inflammation. Immune-modulating properties are partly achieved by affecting T-cell maturation, polarization, and viability. Leptin rises inflammatory cells count, increases proinflammatory cytokine secretion, and impairs regulatory T-lymphocytes differentiation. Leptin secretion and signalization disturbances have recently started to be observed in the context of autoimmunity. In this review, we discuss signaling pathways affected by the satiety hormone, its effect on T-lymphocyte maturation, differentiation and polarization, and relation to other immune-modulating agents. In the end, we highlight the rising evidence connecting hyperleptinemia state which is almost always related to obesity, with autoimmune disorders and take a brief overview of possible mechanisms behind leptin’s potency to induce self-reactivity.

LATE LIVER METASTASIS 20 YEARS AFTER THE INITIAL DIAGNOSIS: A CASE REPORT OF METACHRONOUS HORMONE DEPENDENT TUMORS OF BREAST AND ENDOMETRIUM

Breast cancer is the most common cancer and a significant cause of morbidity and mortality in female population worldwide. The liver is the third most common metastatic site for invasive breast malignancy besides bones, lungs and brain. Breast cancer has been linked with metachronous bone, endometrial, colon/rectal, connective tissue (sarcoma), leukemia, lung, ovary or thyroid cancer. Studies have shown an increased risk of secondary malignancies in women treated for breast malignancy in connection to adjuvant treatment in certain cases. We present a case of a 71 year old woman who was diagnosed with breast cancer 20 years ago. The primary diagnosis was invasive lobular breast cancer localized in left lower lateral quadrant. Micromorphological, histochemical and immunohistochemical analyses rendered diagnosis inconclusive due to lack of tissue so after 4 months rebiopsy was performed. Clinico-pathological correlation of the second biopsy was in favor of liver metastasis of partially hormone dependent breast cancer. Immunohistochemistry was vital for the diagnosis on the liver biopsy, in particular GATA3 positivity and vimentin negative staining which helped us exclude endometrial cancer metastasis which was diagnosed before the initial liver biopsy. GATA 3(+)/vimentin(-) panel proved to be superior to GCDFP-15 and mammaglobin in proving the breast origin of the secondary tumor deposit.Liver metastasis from primary breast cancer can in certain cases occur many years after the initial diagnosis which shows the importance and necessity for long term follow-up of these patients, while considering the possibility of metachronous tumors as well.

EPIDEMIOLOGY AND PROGNOSTIC FACTORS IN PATIENTS WITH SUBDURAL HEMATOMA

SDH was first described in 1658 and in 1914 trauma was recognized as one of the causes. Acute SDH is more common in younger population while chronic is common in the elderly with the peak of incidence of 7.35/100000 per year in the age group 70-79 years. Trauma is one of the main causes of SDH although in 30-50% of patients direct trauma to the head can be omitted. Other predisposing factors include: anticoagulant therapy, epilepsy, and hypertension. The aim of the study was to determine risk factors and prognostic factors for the occurrence of SDH, also to show what age group is most at risk for developing chronic and acute SDH. Identify the diagnostic steps in proving SDH and the best method of treatment. The study includes 267 patients treated in the period from 1.1.2019 to 31.12.2019 at the Clinic for Neurosurgery CCS. SDH was diagnosed by neurological examination and brain CT in all patients and all were treated conservatively or surgically. The analytical statistics were used parametric and non-parametric tests of difference. The study included 185 men and 82 women of middle age 68 ± 17.19 years. Most patients were between 6-8 decades. Multiple changes in CT were observed in 63.3% of patients. Chronic SDH had 50.5% of patients and 45.6% had acute SDH. The most common symptoms were headache, psycho-organic syndrome, and hemiparesis. Patients with a GCS score of more than 8 had a better prognosis and outcome. Surgical treatment was the main course of treatment in our study. CT with / without contrast is the gold standard in detecting SDH. Men are at higher risk for the occurrence of SDH. Symptoms can occur later in the clinical presentation so we need to take caution when performing neurological examination. Factors that can lead us to suspect possible SDH are: age, gender, type of injury, clinical presentation, and time of occurrence.

SELENIUM LEVELS IN PEDIATRIC PATIENTS WITH ENDOCRINE DISEASES: EVIDENCE FROM A SYSTEMATIC REVIEW

Selenium (Se) is essential micronutrient involved in several physiological processes. In many regions around the world, a suboptimal intake of Se has been reported in several health conditions, also in pediatric age. Studies on association between Se level and diseases in children reported contrasting results. We took an aim to perform a systematic review of literature and provide evidence-based conclusion on the magnitude of Se deficit in endocrine diseases in children. PubMed, ISI WoS, and Scopus databases were searched to identify eligible studies, published until July 25, 2019. Methodological quality was assessed using Newcastle–Ottawa Scale. After careful selection, 13 eligible studies were included. Majority were conducted in Turkey (n=5) and Iran (n=5), and sample size varied from 61 to 628 children, with a mean (±SD) age of cases from 5.1±1.6 months up to 13.8±4.5 years. Eleven studies focused on different thyroid diseases, and two on children with type 1 diabetes mellitus (T1DM). In goitrous patients, Se level ranged from mean (±SD), 25.71±20.68 μg/L to 114.9±34.1 μg/L, while in patients with T1DM was 20.9±12.9 μg/mL and mean (95% CI)=58.4 μg/L (55.0–63.09). We may conclude that goiter and thyroid dysfunction are prominent signs of Se deficiency in children. Although deficiency of iodine and selenium are usually combined in some area, our systematic review showed that Se deficiency is important goitrogenic factor in school children. Further randomized controlled trials are needed to adequately explore the role of Se in endocrine disorders in children, across different populations and regions.

PROLACTIN AND HYPERPROLACTINAEMIA IN FEMALE REPRODUCTIVE ENDOCRINOLOGY – AN UPDATE

Hyperprolactinaemia is one of the most frequent causes of anovulation, resulting in infertility and hypoestrogenic state with consequences on overall women’s health. Recent investigations on biological actions of prolactin, especially prolactin of extrapituitary origin, expand our knowledge on prolactin role in the human organism and open new questions connected with female reproductive function and treatment of female infertility. This article represents the review of current knowledge on prolactin physiology, etiopathogenesis, clinical features, assessment , differential diagnosis ,and teatment of hyperprolactinaemia in the female patient.

THE NEW ADDRESSING PROBLEM IN INTESTINAL CANDIDOSIS

Herein, we discussed a new problem concerning diagnosis, treatment and monitoring of patients with intestinal candidosis. The lack of official attitude about significance of Candida overgrowth on intestinal mucosa as well as the absence of guidelines regarding its treatment and required diet, significantly complicate this problem in medical practice. Possible overgrowth of species Saccharomyces cerevisiae-bulardi from probiotics in intestines is a newly recognized problem in diagnostic procedures.

KNOWLEDGE, BELIEFS AND HABITS OF SERBIAN UNIVERSITY STUDENTS REGARDING USAGE OF ANTIBIOTICS – A CROSS-SECTIONAL STUDY OF BIOMEDICAL AND NON-BIOMEDICAL STUDENTS

Proper usage of antibiotics is an often-overlooked subject, leading to a high level of ignorance among youth towards this important topic. The aim of this study was to examine the knowledge, beliefs, and habits of students at Nis University regarding the usage of antibiotics and discover whether an anticipated difference existed between knowledge and habits of biomedical students and that of non-biomedical students. The data were acquired through an online questionnaire that addressed knowledge, beliefs, and habits regarding antibiotics. The study adhered to the principles of the Helsinki declaration. Data were separated into two groups and tested for statistical significance using the Chi-squared test. The questionnaire showed that the majority of students (76.86%) were able to correctly identify bacteria as the main target of antibiotics. More students from non-biomedical faculties thought viral infections could be treated with antibiotics (37.35% vs. 7.06% of medical, p<0.05), and identified incorrectly Paracetamol as an antibiotic (42.17% vs. 8.15% of medical, p<0.05). However, a similar percentage in both groups (49.14%) claimed they interrupted their regimen before the prescribed time, and as much as 67.39% of biomedical students acquired antibiotics with no prescription. Biomedical students demonstrated much better knowledge and beliefs on antibiotics, however, students from both groups were found to have similar habits regarding the usage. The results are similar to available studies from the developing world. A large percentage of students tampers with antibiotics on their own. Campaigns are necessary to inform students better on the subject.

HEMOSTATIC ABNORMALITIES IN COVID-19: UNDERLYING MECHANISMS AND CLUES TO TREATMENT Do we Really See a “Storm” Never Seen Before?

Despite relatively short time since Covid-19 infection has appeared in the world, enormous amount of literature data (more than 20 000 articles currently (mid-June)) is available on PubMed. Those data, together with our own experience at Karolinska University Hospital point towards hemostatic abnormalities in significant number of severe patients. Majority of those patients experience persistent hypercoagulation with massively increased D-dimer and fibrinogen. As a consequence, clinical thrombotic events, including venous thromboembolism (VTE) are common in Covid-19 patients and it seems that increased anticoagulant prophylaxis may be beneficial for severe (ICU/mechanical ventilation) patients. The lungs are most severely injured by the virus and that the potential underlying mechanism is a crosstalk between inflammation/complement and hemostasis. It is important to emphasize that the importance of hemostatic abnormalities in Covid-19 patients should not be overestimated since thromboembolic phenomena are, to a similar extent, present in other influenza and severely ill patients.