Role of CDK4/6 inhibitors in metastatic hormon positive HER2 negative breast cancer treatment

Primjena inhibitora CDK4/6 u liječenju hormonski ovisnoga metastatskog raka dojke negativnog na HER-2 dovela je do bitnog poboljšanja kontrole bolesti, i to ponajprije znatnim produljenjem preživljenja bez progresije bolesti, uz prihvatljiv profil toksičnosti. Osnovno djelovanje inhibitora CDK4/6 jest odgađanje razvoja rezistencije na endokrinu terapiju, odnosno reverziju već nastale rezistencije. Medijani preživljenja bez progresije bolesti kreću se oko 20 i više mjeseci u prvoj liniji liječenja i 10-ak mjeseci i više u drugoj liniji. U prvoj liniji liječenja kombinirani su s aromataznim inhibitorima, a u drugoj s fulvestrantom. Produljenjem vremena bez napredovanja bolesti odgađa se primjena kemoterapije, a bolesnicama se osigurava bolja kvaliteta života. Zbog svega navedenoga ovi lijekovi u kombinaciji s endokrinom terapijom nova su, visokovrijedna terapijska opcija u liječenju metastatskog raka dojke. Međutim, ostaju brojna otvorena pitanja za svakodnevnu kliničku praksu kao što su optimalan odabir bolesnica za prvolinijsko i drugolinijsko liječenje, sekvenciranje drugih lijekova nakon progresije bolesti na inhibitore CDK4/6 te dostupnost i cijena liječenja.Implementation of CDK4/6 inhibitors in metastatic hormone receptor positive, HER2 negative breast cancer treatment significantly improves progression free survival. CDK4/6 inhibitors are characterized by favorable toxicity profile. CDK4/6 inhibitor administration delays and/or overcomes endocrine therapy resistance in metastatic breast cancer. CDK4/6 inhibitors were tested in both first line treatment in combination with aromatase inhibitors, and in second line treatment in combination with fulvestrant. Progression free survival longer than 20 months in the first and longer than 10 months in the second treatment line has been achieved. Progression free survival prolongation may delay chemotherapy administration and consequently enable longer period with maintained quality of life. CDK4/6 inhibitors in combination with endocrine therapy represent a new valuable treatment option for metastatic hormone receptor positive HER2 negative breast cancer. However , many questions such as optimal patient selection as well as positioning of the CDK4/6 inhibitors and other endocrine therapy options during the course of metastatic disease treatment, remain unanswered. Furthermore, availability and cost of CDK4/6 inhibitors are also important issues

MEHANICAL PLANTING OLIVE TREES USING LASER AND GPS METHODS

U radu su prezentirani rezultati strojne sadnje masline pomoću različitih sustava održavanja pravca (laser i GPS) i pogona sadnog aparata (žica i elektro-hidro pogon). Istraživanje usporedbe navedenih strojeva provedeno je tijekom sadnje maslina, sorte Oblica, na području Ninskih stanova (Zadar) 2012. godine. Utvrđene su značajne razlike u učinku sadnje. Kod primjene lasera ostvaren je učinak sadnje od 1,57 ha/h, dok je kod GPS metode učinak sadnje bio 2,32 ha/h. Utvrđeno je da značajnih razlika u kvaliteti sadnje kod obje sadilice nema. Kompjutorskim programima moguće je na temelju uzetih točaka na terenu pomoću GPS-a definirati konfiguraciju terena i nacrtati budući nasad u 3D obliku.The paper presents the results of mechanical planting olive trees using different systems to maintain direction (laser and GPS) and running of plant propagation apparatus (wire and electro-hydro plant). Research comparing these machines was carried out while planting olive trees in the surrounding of the city Zadar (Ninski Stanovi). Planted variety was Oblica and planting was done in the year 2012. Conducted research revealed significant differences in productivity between the planters with laser guidance system and the ones with a GPS system. Planting efficiency was better using GPS (2.32 ha/h) than using laser technique (1.57 ha/h). Significant differences were not found in the quality of planting between planting systems. Computer programs can on the basis of points in the field using GPS, define the configuration of the terrain and draw on orchard in 3D

Epidemiology of Hypothyroidism, Hyperthyroidism and Positive Thyroid Antibodies in the Croatian Population

Thyroid dysfunction appears to be the leading endocrine disorder. We conducted a cross-sectional study on 4402 individuals from three Croatian cohorts. The aim of this study was to analyse the prevalence of diagnosed and undiagnosed hypothyroidism, hyperthyroidism (subclinical and clinical) and positive thyroid antibodies in the Croatian population. The results of the study indicated that 17.6% of participants were euthyroid with positive antibodies. The prevalence of clinical and subclinical hypothyroidism was 3% and 7.4%, respectively, while the prevalence of clinical and subclinical hyperthyroidism was 0.2% and 1.1%, respectively. Among them, 92.6% subclinical hypothyroid, 93.9% clinical hypothyroid, 83% subclinical hyperthyroid and 71.4% clinical hyperthyroid participants were undiagnosed. Finally, the prevalence of undiagnosed subclinical and clinical hypothyroidism in our population was 6.9% and 2.8%, respectively, while the prevalence of undiagnosed subclinical and clinical hyperthyroidism was 0.9% and 0.1%, respectively. Women showed a higher prevalence of thyroid disorders; 1.57 times higher odds of euthyroidism with positive antibodies, 2.1 times higher odds of subclinical hyperthyroidism, 2.37 times higher odds of clinical hypothyroidism and 1.58 times higher odds of subclinical hypothyroidism than men. These results indicate an extremely high proportion of undiagnosed cases, and therefore require investments in a prevention programme