Renal cell carcinoma: molecular pathways and targeted therapy

Renal cell carcinoma (RCC) is not a single disease. A number of different types of cancer occur in the kidney and each is caused by different genes with different histology and clinical course. Studies of hereditary kidney cancer sydromes have led to identification of the main kidney cancer genes: VHL, MET, FH, SDH, FLCN, TSC1 and TSC2. Mutations in each of these genes lead to dysregulation of at least one metabolic pathway that is mediated by oxygen, iron, energy and nutrient sensing suggesting that renal cell cancer is a disease of dysregulated cellular metabolism. A more improved understanding of molecular pathways has led to development of targeted therapies. Targeted agents against VEGF, VEGFR and mTOR continue to play a crucial role in the management of metastatic RCC. However, complete response is extremely rare, resistance in tumor cells develops frequently and adverse effects of therapy are not unusual finding. For that reason further genetic and epigenetic changes, metabolic aberrations as well as immune response are beeing investigated in numerous studies to find new targets for more personalized therapy

THE FIRST WAVE OF THE COVID-19 PANDEMIC AND ITS IMPACT ON THE LEVEL OF DISTRESS IN PATIENTS WITH BREAST CANCER, A MULTICENTRIC STUDY

Background: Information on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), later termed coronavirus disease (COVID-19), first emerged by the end of 2019. As the pandemic spread, cancer patients were immediately recognized as a high-risk population with regard to COVID-19 infection. Moreover, epidemiological measures, like social distancing and lockdowns, additionally burdened patients with cancer. Even outside pandemic breast cancer patients are prone to psychological distress with prevalence ranging approximately 20-40%. This multicentric study aimed to examine the impact of COVID-19 pandemic on the level of distress among breast cancer patients in Croatia while the first wave of COVID-19 pandemic. Subjects and methods: Fife hundred forty-five breast cancer patients were offered to participate in the study. A total of two hundred and one patient, with disease stages ranging I-IV, completed the questionnaire. The questionnaire consisted of disease and socio-demographic characteristics followed by the Distress Thermometer and a problem list. The cut off value of 4 was used to define the high level of distress within Distress Thermometer. Results: High distress level was reported in 54.2% of patients. The most significant problems reported by the participants of our study affected emotions, causing worry, sadness, depression, fear, and nervousness. Additionally, specific practical problems emerged (e.g., child care, housing, and work/school), most probably partly due to the lockdowns and social distancing. Interestingly enough, none of the socio-demographic or disease characteristics were linked to the level of distress. Conclusions: During first wave of COVID-19 pandemic more than half of breast cancer patients, undergoing active oncologic treatment, experienced a high level of distress. Therefore, distress driven by the COVID-19 pandemic should be promptly addressed and additional psychological and social support, targeting specific practical and emotional problems, should be provided for those patients. All the more so as global COVID-19 pandemic far exceeded the duration of the first wave

THE FIRST WAVE OF THE COVID-19 PANDEMIC AND ITS IMPACT ON THE LEVEL OF DISTRESS IN PATIENTS WITH BREAST CANCER, A MULTICENTRIC STUDY

Background: Information on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), later termed coronavirus disease (COVID-19), first emerged by the end of 2019. As the pandemic spread, cancer patients were immediately recognized as a high-risk population with regard to COVID-19 infection. Moreover, epidemiological measures, like social distancing and lockdowns, additionally burdened patients with cancer. Even outside pandemic breast cancer patients are prone to psychological distress with prevalence ranging approximately 20-40%. This multicentric study aimed to examine the impact of COVID-19 pandemic on the level of distress among breast cancer patients in Croatia while the first wave of COVID-19 pandemic. Subjects and methods: Fife hundred forty-five breast cancer patients were offered to participate in the study. A total of two hundred and one patient, with disease stages ranging I-IV, completed the questionnaire. The questionnaire consisted of disease and socio-demographic characteristics followed by the Distress Thermometer and a problem list. The cut off value of 4 was used to define the high level of distress within Distress Thermometer. Results: High distress level was reported in 54.2% of patients. The most significant problems reported by the participants of our study affected emotions, causing worry, sadness, depression, fear, and nervousness. Additionally, specific practical problems emerged (e.g., child care, housing, and work/school), most probably partly due to the lockdowns and social distancing. Interestingly enough, none of the socio-demographic or disease characteristics were linked to the level of distress. Conclusions: During first wave of COVID-19 pandemic more than half of breast cancer patients, undergoing active oncologic treatment, experienced a high level of distress. Therefore, distress driven by the COVID-19 pandemic should be promptly addressed and additional psychological and social support, targeting specific practical and emotional problems, should be provided for those patients. All the more so as global COVID-19 pandemic far exceeded the duration of the first wave

Praćenje onkoloških bolesnika – kliničke preporuke Hrvatskog društva za internističku onkologiju HLZ-a 1. Dio: rak dojke, rak tijela maternice, rak vrata maternice, rak jajnika [Cancer patients follow-up – Croatian society of medical oncology clinical guidelines Part I: breast cancer, uterine cancer, cervical cancer, ovarian cancer]

Treatment of oncological patients must be based upon multidisciplinary approach, and takes place in specialized oncological centers. By the end of a specifi c oncological treatment further follow-up is managed mostly by the oncologists, but the role of the general practitioners becomes more important every day and therefore should be precisely defi ned. Nowadays, most of the existing follow-up guidelines are not based on prospective studies, but on the experts opinion of a particular oncological center or specialists. The aim of the Croatian Society of Medical Oncology (CSMO) with these recommendations is to standardise and rationalise the diagnostic procedures algorithm in the follow-up of oncological patients after primary treatment

CANCER PATIENTS FOLLOW-UP – CROATIAN SOCIETY OF MEDICAL ONCOLOGY CLINICAL GUIDELINES Part I: breast cancer, uterine cancer, cervical cancer, ovarian cancer

Liječenje onkoloških bolesnika mora se temeljiti na multidisciplinarnom pristupu, a provodi se u specijaliziranim onkološkim centrima. Nakon završetka specifičnog onkološkog liječenja daljnje praćenje uglavnom provode onkolozi, ali je uloga liječnika primarne zdravstvene zaštite (PZZ) sve važnija i potrebno ju je jasno definirati. Trenutačno se većina preporuka za praćenje ne temelji na prospektivnim studijama, već se zasniva na stručnim mišljenjima pojedinih onkoloških centara ili specijalista. Hrvatsko društvo za internističku onkologiju (HDIO) ovim preporukama želi standardizirati i racionalizirati dijagnostičke postupke u praćenju onkoloških bolesnika nakon završetka primarnog liječenja.Treatment of oncological patients must be based upon multidisciplinary approach, and takes place in specialized oncological centers. By the end of a specific oncological treatment further follow-up is managed mostly by the ­oncologists, but the role of the general practitioners becomes more important every day and therefore should be precisely defined. Nowadays, most of the existing follow-up guidelines are not based on prospective studies, but on the experts ­opinion of a particular oncological center or specialists. The aim of the Croatian Society of Medical Oncology (CSMO) with these recommendations is to standardise and rationalise the diagnostic procedures algorithm in the follow-up of oncological patients after primary treatment

Mjesto i važnost nekliničkih bolničkih centara u liječenju bolesnika sa zloćudnim bolestima u Republici Hrvatskoj

Onkologija predstavlja važan segment sveukupnoga hrvatskoga zdravstvenog sustava. Sama onkologija jedna je od trenutačno najpropulzivnijih medicinskih struka te smo svakodnevno svjedoci ekspanzivnog rasta novih modaliteta onkološkog liječenja. Ove činjenice nameću imperativ stvaranja onkološke mreže koja bi kao zadatak imala standardiziranje onkološkog liječenja i osiguravanje dostupnosti novih modaliteta liječenja za sve oboljele od zloćudnih bolesti, neovisno o njihovom mjestu boravka.¹ Hrvatska već ima prepoznate i definirane regionalne onkološke centre u sklopu kliničkih bolničkih centara u Zagrebu, Rijeci, Osijeku i Splitu. Nasreću, u Hrvatskoj postoji tradicija, stara nekoliko desetljeća, razvoja onkoloških centara u općim i županijskim bolnicama. Poimence, to su neklinički onkološki centri u Županijskoj bolnici Čakovec, Općoj bolnici Dubrovnik, Općoj bolnici Karlovac, Općoj bolnici Koprivnica, Općoj bolnici Pula, Općoj bolnici Slavonski Brod, Općoj bolnici Šibenik, Općoj bolnici Varaždin i Općoj bolnici Zadar. Svrha ovoga istraživanja, provedenog u svim nekliničkim onkološkim centrima Hrvatske te korištenjem podataka Državnog zavoda za statistiku i Hrvatskog zavoda za zdravstveno osiguranje, bila je uvidjeti kako je trenutno organizirana onkološka skrb u Republici Hrvatskoj i koja je uloga nekliničkih onkoloških centara u liječenju bolesnika sa zloćudnim bolestima u Republici Hrvatskoj

Development and the initial validation of a new self-administered questionnaire for an early detection of health status changes in smokers at risk for chronic obstructive pulmonary disease (MARKO questionnaire)

Aim To develop and do an initial validation of a new simple tool (self-administered questionnaire) that would be sensitive and specific enough to detect early changes in smokers leading to future development of chronic obstructive pulmonary disease (COPD). Methods 224 consecutive participants (50.9% women), with mean ± standard deviation age of 52.3 ± 6.7 years, 37.5 ± 16.7 pack-years smoking history (85.8% active smokers), and no prior diagnosis of COPD were recruited. The MARKO questionnaire was self-administered twice; at the general practitioner’s office and after 2-4 weeks at the tertiary care hospital. Participants were assessed for COPD by a pulmonologist after filling in a quality of life (QoL) questionnaires, historytaking, physical examination, lung function test, 6-minute walk test, and laboratory tests. They were divided into four subgroups: “healthy” smokers, symptomatic smokers, and smokers with mild and moderately severe COPD. Results Psychometric analyses indicated that the 18-item questionnaire had a very good internal consistency (Cronbach’s alpha = 0.91) and test-retest reliability for a four week period (ρc = 0.89, 95% confidence interval [CI] 0.85-0.92, Lin’s concordance). A significant correlations of MARKO scores were found with two QoL questionnaires; r = 0.69 (P < 0.001) and r = 0.81 (P < 0.001). Receiver operating characteristic curve analysis showed an area under the curve of 0.753 (95% CI 0.691-0.808, P < 0.001), with a sensitivity of 71.83% and specificity of 64.24% to discriminate “healthy” smokers from other subgroups. Conclusion Based on psychometric analyses and high convergent validity correlation with already validated QoL questionnaires, the newly developed MARKO questionnaire was shown to be a reliable self-administered short health status assessment tool

FINANCIRANJE MSP IZ SUBVENCIONIRANIH IZVORA – PRIMJER NA ODABRANOM PODUZEĆU : diplomski rad

Mala i srednja poduzeća može se nazvati kamenjem temeljcem ekonomije. Radi se o ekonomiji općenito, sektoru malog gospodarstva Splitsko - dalmatinske županije, gospodarstvu Republike Hrvatske, sektoru malog gospodarstva na razini Europske Unije, a i svjetskoj ekonomiji u cijelosti. Kao prevalentni oblik organizacije subjekata gospodarstva, koji čini čak 95% do 99% ukupnog broja poduzeća na globalnoj razini, MSP predstavljaju enormne kreatore radnih mjesta, te izvor ekonomskog rasta i fleksibilnosti gospodarstava, promotori su povećane kompetitivnosti na tržištu i predvodnici su uvođenja novih tehnika i novih proizvoda. U svijetu koji viđa promjene brže nego ikada, potiče tržišno natjecanje i globalnu trgovinu, MSP imaju prednost fleksibilnosti i prilagodljivosti, što im otvara prostor za nove ideje i povećanu kreativnost. No, karakteristike koje osiguravaju prednosti za MSP istovremeno predstavljaju prepreke s kojima se velika poduzeća ne moraju susretati. Brojna istraživanja su pokazala da je najveća prepreka u poslovanju MSP upravo pristup financiranju. Ovaj rad se fokusira na prikazivanje pozitivnih utjecaja vanjskih potpora pri financiranju MSP, kao i navođenje svih promjena za rast i razvoj gospodarstva uzrokovanih navedenom pomoći.Small and medium enterprises deserve to be called the cornerstone of economy. Not just any economy, economy in general. Wether it is the small business sector of Split - Dalmatia County, the Croatian economy, the small business sector of the European Union, or the global economy as a whole. As the prevalent type of business structure that makes up from 95% to 99% of all businesses structures globally, SMEs work as enormous creators of new employment, sources of economic growth and flexibility, promotors of market competitiveness and front-runners in developing new techniques and products. In a world that changes faster than ever, a world that encourages market competitiveness and global trade, SMEs have an advantage of being flexible and adaptable, which leaves them space for new ideas and increased creativity. Unfortunately, the same characteristics that are advantageous for SMEs are usually the causes of hurdles they have to cross. The same hurdles that are usually bypassed by large corporations. Many a research has shown that the biggest obstacle in the life of a SME is the access to financial resources. This thesis focuses on showing the positive effects of external financial support of SMEs and all of the resulting changes in the growth and development in the economy