KIDNEY CANCER IN CROATIA - TRENDS IN INCIDENCE AND MORTALITY IN THE 21ST CENTURY.

Kidney cancer is estimated to be responsible for more than 400 000 new cancer cases and 180 000 cancer deaths a year. Its incidence is increasing in the majority of developed countries, due to an increased prevalence of recognized risk factors such as smoking, alcohol use and obesity, as well as incidental findings on unrelated diagnostic imaging procedures. Mortality is decreasing in the majority of European countries, due to improvements in treatment and stage at diagnosis shift with more tumors being diagnosed at an early stage. In this paper, we present kidney cancer incidence and mortality trends in Croatia using joinpoint regression analysis. The incidence was rising throughout the 2001-2019 period, with an annual percent change (APC) of 2.5%; more so in men (APC of 2.5%) than in women (APC of 2.2%). Mortality increased during the 2001-2014 period (APC of 2.4%), but started to decrease in recent years (APC -2.7%, 2014-2020). Unlike sex differences observed in other European countries, with more favorable mortality trends found in women, our study showed a constant increase in mortality in women (APC of 1.2%) and a recent decrease in mortality in men, starting in 2013 (APC of -2.8%), after a period of increase from 2001 (APC of 3.3%).

AMIODARONE AND THYROID DYSFUNCTION.

Thyroid gland has a key role in maintaining the body homeostasis. Thyroxine is the main hormone secreted from the thyroid gland, its effect being predominantly achieved after the intracellular conversion of thyroxine to triiodothyronine, which exhibits a higher affinity for the receptor complex, thus modifying gene expression of the target cells. Amiodarone is one of the most commonly used antiarrhythmics in the treatment of a broad spectrum of arrhythmias, usually tachyarrhythmias. Amiodarone contains a large proportion of iodine, which is, in addition to the intrinsic effect of the medication, the basis of the impact on thyroid function. It is believed that 15%-20% of patients treated with amiodarone develop some form of thyroid dysfunction. Amiodarone may cause amiodarone-induced hypothyroidism (AIH) or amiodarone-induced thyrotoxicosis (AIT). AIT is usually developed in the areas with too low uptake of iodine, while AIH is developed in the areas where there is a sufficient iodine uptake. Type 1 AIT is more common among patients with an underlying thyroid pathology, such as nodular goiter or Graves' (Basedow's) disease, while type 2 mostly develops in a previously healthy thyroid. AIH is more common in patients with previously diagnosed Hashimoto's thyroiditis. Combined types of the diseases have also been described. Patients treated with amiodarone should be monitored regularly, including laboratory testing and clinical examinations, to early detect any deviations in the functioning of the thyroid gland. Supplementary levothyroxine therapy is the basis of AIH treatment. In such cases, amiodarone therapy quite often need not be discontinued. Type 1 AIT is treated with thyrostatic agents, like any other type of thyrotoxicosis. If possible, the underlying amiodarone therapy should be discontinued. In contrast to type 1 AIT, the basic pathophysiological substrate of which is the increased synthesis and release of thyroid hormones, the basis of type 2 AIT is destructive thyroiditis caused by amiodarone, desethylamiodarone as its main metabolite, and an increased iodine uptake. Glucocorticoid therapy is the basis of treatment for this type of disease.

Anxiety and Depression as Comorbidities of Multiple Sclerosis.

Multiple Sclerosis (MS), a chronic inflammatory neurodegenerative disease, is accompanied by a number of comorbidities. Among the psychiatric ones, depression and anxiety occupy a special place. It is estimated that the prevalence of anxiety in the MS population is 22.1% verus 13% in the general population; whereas the prevalence of anxiety levels, as determined by various questionnaires, reaches even 34.2%. Systematic literature reviews (SPL) show considerable data variations due to differences in study design, sample size, diagnostic criteria and extremely high heterogeneity (I2). Among the more conspicuous factors associated with anxiety disorder in MS are demographic factors (age and gender), nonsomatic depressive symptoms, higher levels of disability, immunotherapy treatments, MS type, and unemployment. Depression is the most common psychiatric commorbidity in MS and the lifetime risk of developing depression in MS patients is >50%. According to some research, the prevalence of depression in MS vary between 4.98% and 58.9%, with an average of 23.7% (I2=97.3%). Brain versus spinal cord lesions, as well as temporal lobe, fasciculus arcuatus, superior frontal and superior parietal lobe lesions in addition to the cerebral atrophy have been shown to be the anatomical predictors of depressive disorder in MS. Hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA) and the consequent dexamethasone-insupressible hypercortisolemia, in addition to cytokine storm (IL-6, TNF-α, TGFß1, IFNγ/IL-4) present the endocrine and inflammatory basis for development of depression. Fatigue, insomnia, cognitive dysfunction, spasticity, neurogenic bladder, pain, and sexual dysfunction have shown to be additional precipitating factors in development of anxiety and depression in MS patients.