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Survivin Expression in Placentas with Intrauterine Growth Restriction
No full textBackground/Objectives: Intrauterine growth restriction (IUGR) is a pathological condition defined by a reduced fetal ability to achieve the genetically expected growth potential during gestation. It affects 5–10% of all pregnancies and it is a leading cause of perinatal morbidity and mortality. During the initial phases of placentation, complex interlinked processes including cell proliferation, differentiation, apoptosis and the invasion of trophoblasts occur. Alterations in the regulation of these processes lead to placental dysfunction. Survivin, a member of the inhibitor of apoptosis (IAP) family, plays an important role in cell proliferation balance and apoptosis, thus leading to proper placental development. This study aimed to evaluate survivin expression in placentas from IUGR and healthy pregnancies to explore its potential as a biomarker for the early diagnosis, prevention, and treatment of IUGR. Methods: Survivin presence was determined in 153 archival formalin-fixed and paraffin-embedded placental tissues from IUGR (N = 122) and uncomplicated (N = 31) term pregnancies. Tissue microarrays (TMAs) were constructed, and survivin expression was assessed using immunohistochemistry (IHC). Survivin levels were quantified using positive cell proportion (PCP) scores and immunoreactive scores (IRS), with statistical significance determined using mean values, standard deviation (SD), standard error, and Student’s t test in instances of normal distribution, and when this was not the case, the Mann–Whitney test. Chi-square tests, Fisher exact tests, and t-tests (p < 0.05) were used to compare categorical variables. Results: Our results suggested the significantly higher expression of survivin validated with PCP (p < 0.001) and IRS (p < 0.002) in placentas with IUGR compared to placentas from non-complicated term pregnancies. Conclusions: Increased survivin expression in IUGR placentas points to its potential role as a key indicator of placental dysfunction. By signaling early pathological changes, survivin may offer a valuable tool for the early detection of IUGR, potentially allowing for timely clinical interventions that could reduce the risk of serious outcomes, including stillbirth. To fully establish survivin’s clinical value, further research is needed to validate its diagnostic accuracy and to explore its involvement in molecular pathways that may be targeted for therapeutic benefit
Concordance of HER2-low scoring in breast carcinomas among pathologists
No full textBreast cancers represent a diverse array of tumors characterizide by significant differences in morphology,
molecular profiles, clinical presentations, biological behaviours, and therapeutic responses1. Treatment decisions
primarily rely on the clinical stage of the disease and the outcomes of conventional biomarker analysss, which
include assessment of estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2),
and proliferative marker Ki67
Femicide in 21st century : graduation thesis
No full textThis thesis explores femicide as a serious and growing form of gender-based violence in the 21st century. It examines the historical background, definitions and types of femicide, including intimate partner femicide, honour killings and those linked to organized crime, cultural beliefs and discrimination. The paper highlights the key causes of femicide, such as gender inequality, control and social norms and emphasizes how cultural, religious and economic factors play a significant role in its occurrence. A major part of the thesis focuses on forensic medicine and how it is used to investigate femicide cases. It explains different types of trauma, signs of death, autopsy techniques and how experts distinguish between homicide, suicide and accidental deaths. The thesis also presents global and European statistics on femicide and shows that many cases are preventable, often involving prior abuse or warning signs that were ignored.The discussion also covers the impact of the COVID-19 pandemic, which increased domestic violence and femicide rates due to isolation, economic stress and limited access to support. Finally, the paper stresses the importance of early intervention, legal protection and cultural change to prevent femicide and save lives
Clinical evaluation and treatment of patients with papillary renal cell carcinoma
No full textZbog slučajnih otkrića malih bubrežnih tvorbi tijekom abdominalnih pregleda, učestalost raka bubrega danas je u porastu. Papilarni karcinom bubrežnih stanica (pRCC) je drugi najčešći tip karcinoma bubrega. U početnim fazama mnogi pacijenti nemaju simptome, no kasnije mogu imati bolove u lumbalnoj regiji, hematuriju, gubitak težine, noćno znojenje i druge simptome. Rizični čimbenici uključuju pušenje, hipertenziju, pretilost i obiteljsku povijest raka te različite stadije bubrežne disfunkcije. Morfološka klasifikacija pRCC-a je izazovna zbog postojanja mješovitih tumora tipa 1 i 2. PRCC1 povezan je s prekomjernom ekspresijom MET gena i obično ima indolentan tijek. S druge strane, tip 2 manje je povezan s MET mutacijama i ima lošiju prognozu. S obzirom na češće otkrivanje manjih tumora, preferiraju se nefron-poštedne operacije. Parcijalna nefrektomija je preporučena metoda za lokalizirani pRCC. Kod metastatskog pRCC-a prognoza je lošija. Terapija citokinima pokazala se manje učinkovitom pa je imunoterapija zamijenjena ciljanim lijekovima poput cabozantiniba, koji se sada preporučuje kao terapija prvog izbora. Kombinacija lenvatiniba i pembrolizumaba, te cabozantiniba i nivolumaba, pokazale su visoku učinkovitost, a pembrolizumab je doveo do dugoročnog preživljenja kod određenih pacijenata. EAU smjernice za 2025. godinu preporučuju cabozantinib, dok se imunoterapijske kombinacije mogu razmotriti u specifičnim slučajevima, osobito kod pacijenata s MET-alteracijama i dobrom općom prognozom. U ovome radu su prikazane postojeće spoznaje o pRCC-u te specifičnosti u odnosu na druge podtipove RCC-a.Due to the incidental discovery of small renal masses during abdominal examinations, the incidence of kidney cancer is increasing. Papillary renal cell carcinoma (pRCC) is the second most common type of kidney cancer. In the early stages, many patients are asymptomatic, but later they may present with lower back pain, hematuria, weight loss, night sweats, and other symptoms. Risk factors include smoking, hypertension, obesity, and a family history of cancer, as well as varying degrees of renal dysfunction. Morphological classification of pRCC is challenging due to the existence of mixed types 1 and 2 tumors. PRCC1 is associated with overexpression of the MET gene and usually has an indolent course. On the other hand, type 2 is less associated with MET mutations and has a worse prognosis. Given the more frequent detection of smaller tumors, nephron-sparing surgeries are preferred. Partial nephrectomy is the recommended method for localized pRCC. Metastatic pRCC has a worse prognosis. Cytokine therapy proved less effective, so immunotherapy was replaced by targeted drugs such as cabozantinib, which is now recommended as first-line therapy. The combination of lenvatinib and pembrolizumab, and cabozantinib and nivolumab, have shown high efficacy, with pembrolizumab leading to long-term survival in certain patients. The 2025 EAU guidelines recommend cabozantinib, while immunotherapy combinations may be considered in specific cases, especially in patients with MET-alterations and a good overall prognosis. This paper presents the current knowledge about pRCC and its specificities in relation to other subtypes of RCC
Beta thalassemia syndromes: New insights
No full textBeta thalassemia (β-thalassemia) syndromes are a heterogeneous group of inherited hemoglobinopathies caused by molecular defects in the beta-globin gene that lead to the impaired synthesis of beta-globin chains of the hemoglobin. The hallmarks of the disease include ineffective erythropoiesis, chronic hemolytic anemia, and iron overload. Clinical presentation ranges from asymptomatic carriers to severe anemia requiring lifelong blood transfusions with subsequent devastating complications. The management of patients with severe β-thalassemia represents a global health problem, particularly in low-income countries. Until recently, management strategies were limited to regular transfusions and iron chelation therapy, with allogeneic hematopoietic stem cell transplantation available only for a subset of patients. Better understanding of the underlying pathophysiological mechanisms of β-thalassemia syndromes and associated clinical phenotypes has paved the way for novel therapeutic options, including pharmacologic enhancers of effective erythropoiesis and gene therapy
Extreme Thrombocytosis in Patients with Overt Myelofibrosis and Its Clinical Associations
No full textBackground/Objectives: Overt primary myelofibrosis (PMF), secondary post-polycythemia vera (post-PV), and post-essential thrombocythemia (post-ET) myelofibrosis (SMF) are chronic myeloproliferative neoplasms (MPN) that sometimes present with extreme thrombocytosis (ExTh, platelet count > 1000 × 109/L), a phenomenon of uncertain clinical significance since there are no published data available. Methods: We retrospectively investigated the clinical correlations and associated outcomes of ExTh in a cohort of 172 patients with overt myelofibrosis diagnosed in six Croatian hematology centers. Results: ExTh was present in 5.8% of patients and was associated with post-ET etiology of myelofibrosis, older age, smaller spleen size, and the presence of arterial hypertension (p < 0.05 for all analyses). No significant associations were observed with sex, degree of bone marrow fibrosis, or driver mutation status. Over the follow-up period, patients with ExTh experienced a favorable course regarding survival (p < 0.001) and bleeding risk (p = 0.034), whereas no significant association with thrombotic risk was observed (p = 0.682). Conclusions: In contrast to its context in ET, ExTh in overt fibrotic MPN does not appear to confer higher bleeding or thrombotic risk. Instead, it is associated with more favorable survival outcomes and reduced bleeding risk
Time for Change: A 3-Year Prospective Study on Mediterranean Diet Adherence and Body Composition in Kidney Transplant Recipients
No full textBackground: The aim of this prospective follow-up study was to evaluate changes in body composition parameters and Mediterranean diet (MeDi) adherence among kidney transplant recipients (KTRs) over a three-year period. Additionally, this study sought to investigate the associations between these changes and clinical parameters, including laboratory parameters, new onset of diseases, and death outcome. Methods: A total of 116 KTRs were initially assessed in 2019 and subsequently re-evaluated in 2022. The Mediterranean Diet Serving Score (MDSS) was used to assess dietary adherence to the MeDi at baseline and follow-up assessments. Bioelectrical impedance analysis was used to assess body composition and clinical outcomes were assessed by the data available from medical charts. Results: After three years, MeDi adherence significantly decreased (p = 0.028) from 15 (18.29%) to 5 (6%), with dominantly lower adherence for vegetable, fruit, legume, red meat, olive oil and fish intake. Regarding body composition parameters, the most prominent change was seen in muscle mass, which deteriorated from 41.77% (IQR 6.46) to 39% (IQR 6.14; p = 0.004). However, changes in fat mass level were not significant in the follow-up period. Furthermore, cereal intake, fasting blood glucose (FBG), cholesterol level, level of low-density lipoprotein cholesterol (LDL), triglyceride leve and presence of diabetes mellitus lwere shown to be predictive for the decline of skeletal muscle mass. There were no significant changes in the estimated glomerular filtration rate (eGFR) or albuminuria level during the follow-up period. Associations with the death outcome were found for the MeDi-advised intake of eggs (β = −1.06, HR = 0.35, CI (0.14–0.87), p = 0.023), phase angle (PhA) (β = −2.68, HR = 0.07, CI (0.01–0.43), p = 0.004), cholesterol level (β = 0.95, HR = 2.60, CI (1.40–4.70), p = 0.001) and calcium level (β = −7.21, HR = 0.00, CI (0.00–1.50), p = 0.063). Conclusions: This study highlights a significant decline in MeDi adherence and skeletal muscle mass among KTRs over a three-year follow-up period, with no notable changes in fat mass or kidney function. The predictors of muscle mass loss and associations with mortality underscore the importance of dietary and clinical management in this population
The Effect of Coronary Artery Bypass Surgery on Interleukin-18 Concentration and Biomarkers Related to Vascular Endothelial Glycocalyx Degradation
No full textSurgical myocardial revascularization, regardless of the technique used, causes ischemia–reperfusion injury (IRI) in the myocardium mediated by inflammation and degradation of the endothelial glycocalyx (EG). We investigated the difference between on-pump and off-pump techniques in terms of the concentration of proinflammatory interleukin (IL)-18 and the EG degradation products syndecan-1 and hyaluronic acid measured by ELISA in the peripheral and cardiac circulation during open heart surgery and in the early postoperative period. The concentration of IL-18, C-reactive protein (CRP), and cardiac troponin T (cTnT) and the leukocyte count increased statistically significantly in revascularized patients at 24 and 72 h after revascularization compared to the beginning of the procedure and was always statistically significantly higher in on-pump patients. Syndecan-1 and hyaluronic acid only increased in on-pump patients 24 and 72 h after revascularization. IL-18 correlated positively with syndecan-1 and CRP only in the pump setting and with the number of leukocytes in both revascularization regimens 24 and 72 h after the surgery. cTnT and hyaluronic acid did not correlate with IL-18. Our results suggest that IL-18 plays an important role in the early inflammatory response in patients during open heart surgery and in the early postoperative period, leading to additional damage to the EG, while it is probably not responsible for myocardial necrosis. It could serve as a biomarker to identify high-risk patients and as a therapeutic target to reduce inflammation and EG degradation. In addition, measurement of IL-18 could help improve the treatment, recovery, and outcomes of patients after heart surgery
The effect of impaired renal function, increased red cell mass and plasma volume on thrombotic risk in PV patients
No full textMigrenozni moždani udar u djece-mit ili stvarnost : diplomski rad
No full textUvod. Migrena je primarna glavobolja koja se najčešće očituje pulsirajućim bolom lokaliziranim na jednoj strani glave. Tipična je podjela migrene na onu s aurom (MA) i onu bez aure (MO). Migrena je najčešća glavobolja u djece. Napadaj migrene se obično događa u tri faze: premonitorna faza, faza glavobolje i postdromna faza. Kod migrene s aurom se javlja i dodatna faza aure koja se može događati prije ili paralelno s fazom glavobolje. U akutnom liječenju migrene preferiraju se analgetici, dok se za profilaksu najčešće koristi propranolol. Moždani udar kod djece može biti hemoragijski ili ishemični. Migenozni moždani udar jest ishemični moždani udar koji nastaje tijekom tipičnog napadaja migrene s aurom. Svrha rada. Svrha ovog rada je prikazati slučaj migrenoznog moždanog udara u djeteta predpubertetske dobi te raspraviti je li moguća njegova pojava u djece te patogenetske mehanizme koji su doveli do te pojave. Prikaz slučaja. 10-godišnja pacijentica hospitalizira se zbog glavobolje i lijevostrane hemipareze. Nativni CT mozga uredan. Na MR mozga vidi se ishemijska lezija u opskrbnom području srednje moždane arterije. 3D/TOF angiografija intrakranijskih krvnih žila pokazuje okluziju srednje moždane arterije desno u području M1 segmenta. Daljnjom obradom ne nađe se etiološkog uzroka. Na kontrolnoj MRI 3D/TOF angiografiji pred otpust vidi se rekanalizacija zahvaćene arterije. Zaključak. Zbog toga što su ICHD kriteriji uski i mnogo pacijenata ih ne ispunjava, te stoga što su isključeni svi ostali mogući uzroci moždanog udara, smatra se da se pacijentica ipak preboljela migrenozni moždani udar.Introduction. Migraine is a primary headache most commonly manifested as pulsating pain on one side of the head. It can be divided into migraine with aura and migraine without aura. Migraine is the most common headache in children. A migraine attack typically happens in three phases: premonitory phase, headache phase and postdrome phase. In migraine with aura another phase, the aura phase happens before or parallel with headache phase. Analgetics are preferred in acute treatment of migraine, while in prophylaxys propranolol is most commonly used. Stroke in children can be hemorrhagic or ischemic. Migrainous infarction is ischemic stroke happening during a typical attack of migraine with aura. Aim. The aim of this research is to show a case report of a prepuberty child with migrainous infarction and discuss whether its appearance is possible in children. Case report. 10-year old patient is hospitalized due to headache and left side hemiparesis. Native brain CT is normal. Brain MRI shows an ischemic lesion in the supply area of middle cerebral artery. 3D/TOF angiography of intracranial blood vessels shows an occlusion of the middle cerebral artery in the M1 segment area. Further work-up did not find an etiological cause. Control MRI 3D/TOF angiography before discharge shows recanalization of the affected artery. Conclusion. Because the ICHD criteria are narrow and many patients don't meet it, and beacuse all of the other causes of stroke were ruled out, the patient was concludet to have recovered from migrainous infarction