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Anafilaksija i anafilaktički šok u djece : diplomski rad
No full textO anafilaksiji postoje podaci koji datiraju još 2000 godine prije Krista, njezine simptome primijetili su stari Grci, a opisani su i u drevnoj Kineskoj medicinskog literaturi. Naziv anafilaksija skovao je Charles Richet koji je primijetio da protutijela nemaju isključivo zaštitničku ulogu te mogu uzrokovati bolest. Prema podacima Europskog registra za anafilaksiju, 24% upisanih pripada pedijatrijskoj populaciji, dok globalna prevalencija iznosi od 0.04-1.8%. Najveći mortalitet je u periodu adolescencije, iznosi 0.65-2%. Najčešći pokretači anafilaksije u djece jesu prehrambeni proizvodi (mlijeko i mliječni proizvodi, kikiriki, lješnjak i drugi), lijekovi (beta laktamski antibiotici, NSAR-i) te ubodi insekata. Anafilaksija je najteži tip preosjetljivosti tipa I, posredovana alergenima koji uzrokuju degranulaciju mastocita i bazofila, oslobađajući velike količine histamina i drugih medijatora s bronhokonstrikcijim, vazodilatacijskim i transudacijskim učinkom, zahvaljujući kojima nastaju karakteristični simptomi anafilaksije. U slučaju pretjerane i neliječene vazodilatacije dolazi do razvoja jednog od oblika distribucijskog šoka; anafilaktički šok sa svojom mogućom kompenziranom, dekompenziranom i ireverzibilnom fazom. Klinička slika ovisi o putu unosa alergena, dozi i stupnju senzibilizacije. Najteža klinička slika nastaje nakon intravenskog unosa alergena. Anafilaksija je isključivo klinička dijagnoza, a zbrinjavanje se vrši ABCDE metodom. Glavni i nezaobilazni lijek je adrenalin apliciran intramuskularno koji se ponavlja svakih 5-10 minuta ovisno o odgovoru. Refraktorna anafilaksija ili šok zahtjeva liječenje u jedinicama intenzivnog liječenja uz kontinuirano monitoriranje vitalnih funkcija, davanje intravenskog adrenalina i bolusa tekućina. Učinci šoka manifestiraju se disfunkcijom, potom i zatajenjem svih organskih sustava ukoliko se navedeno ne uspije terapijski zaustaviti. Prije otpusta potrebno je educirati bolesnika i njegovu obitelj o korištenju samoinjektora adrenalina i napraviti detaljan alergološki plan kako bi se smanjio rizik hospitalizacije.Historical records of anaphylaxis date back as early as 2000 BC. The ancient Greeks were among the first to recognize its symptoms, and references to anaphylactic-like reactions can also be found in classical Chinese medical literature. The term “anaphylaxis” was coined by Charles Richet, who discovered that antibodies are not solely protective but can also induce severe pathological reactions. According to the European Anaphylaxis Registry, approximately 24% of cases occur within the pediatric population. The global prevalence of anaphylaxis ranges from 0.04% to 1.8%, with the highest mortality rates observed during adolescence, estimated at 0.65% to 2%. In children, the most common triggers for anaphylaxis include food products (such as milk and dairy, peanuts, hazelnuts, and others), medications (particularly beta-lactam antibiotics and non-steroidal anti-inflammatory drugs), and insect stings. Anaphylaxis represents the most severe form of type I hypersensitivity reaction. It is mediated by allergens that trigger the degranulation of mast cells and basophils, releasing significant amounts of histamine and other inflammatory mediators. These substances lead to bronchoconstriction, vasodilation, and transudation, resulting in the characteristic clinical symptoms of anaphylaxis. If vasodilation is excessive and left untreated, it can lead to a distributive form of shock known as anaphylactic shock. This condition progresses through compensatory, decompensated, and eventually irreversible phases. The clinical presentation of anaphylaxis depends on the route of allergen exposure, the dose, and the individual’s level of sensitization. The most severe reactions occur with intravenous exposure to allergens. Anaphylaxis is a clinical diagnosis, meaning it relies on the recognition of symptoms rather than laboratory confirmation. Emergency management follows the ABCDE (Airway, Breathing, Circulation, Disability, Exposure) approach. The cornerstone of treatment is intramuscular adrenaline, which should be administered promptly and repeated every 5–10 minutes depending on the patient’s response. Refractory anaphylaxis or anaphylactic shock requires intensive care treatment, including intravenous adrenaline administration, fluid boluses, and continuous monitoring of vital signs. In such cases, shock can lead to multi-organ dysfunction and eventually failure. Before discharge, it is essential to educate patients and caregivers on the proper use of adrenaline auto-injectors. A detailed allergology action plan should also be provided to reduce the risk of future hospitalizations
The impact of iglF gene of Francisella tularensis LVS strain on the expression of pro-inflammatory cytokines : graduation thesis
No full textFrancisella tularensis subsp. holarctica is a very infectious gram-negative bacterium and the causative pathogen of tularemia, a zoonotic disease with diverse clinical manifestations. Its virulence largely depends on the Francisella Pathogenicity Island (FPI), which encodes components of the Type VI Secretion System (T6SS), essential for intracellular survival and immune evasion. This study investigates the role of the iglF gene, a putative effector protein within the FPI, and its impact on the expression of inflammatory cytokines after infection.
Using immortalized murine bone marrow-derived macrophages infected with F. tularensis subsp. holarctica LVS, ΔiglF mutant and LPS, the mRNA expression levels of TNF, IL-1β, and IL-10 were quantified at 6- and 24-hours post-infection via RT-PCR.
Results showed a statistically significant reduction in the expression of TNF and IL-10 in ΔiglF-infected cells compared to LVS at 6 hours post-infection. At 24 hours, TNF and IL-1β expression remained significantly lower in ΔiglF infected cells. These findings imply that iglF plays a crucial role in cytokine production during infection, likely contributing to F. tularensis virulence and its ability to influence host immunity.
The study highlights the importance of iglF in immune modulation, although its exact mechanism and role in phagosomal escape, intracellular replication, and host cell death require further in vivo investigation. Understanding the function of iglF could inform therapeutic strategies and vaccine development against F. tularensis
Autoimmune thyroiditis: pathogenesis, diagnosis and treatment
No full textAutoimuni tireoiditis najčešća je autoimuna bolest u ljudi, a uključuje dva glavna klinička entiteta – Hashimotov tireoiditis (HT) i Gravesovu bolest (GD). Riječ je o organski specifičnim poremećajima koje karakterizira limfocitna infiltracija i prisutnost autoantitijela usmjerenih na specifične komponente tireocita. Dok HT vodi do hipotireoze uslijed destrukcije žljezdanog parenhima, GD izaziva hipertireozu potaknutu stimulirajućim protutijelima na TSH receptor. Dijagnoza se temelji na laboratorijskim testovima, ultrazvuku i scintigrafiji štitnjače.
Patogeneza autoimunog tireoiditisa uključuje kompleksnu interakciju genetskih predispozicija (HLA, CTLA-4), okolišnih čimbenika (pušenje, unos joda) i disfunkcije imunološkog nadzora, osobito T limfocita i prirodnih stanica ubojica (NK). U kliničkoj slici dominiraju nespecifični simptomi – anksioznost, umor, promjene tjelesne mase – što otežava pravovremenu dijagnozu. Terapijski pristupi uključuju farmakološko liječenje (antitireoidni lijekovi, levotiroksin), radiojodnu terapiju i tireoidektomiju, ovisno o fenotipu bolesti.
Poseban naglasak stavljen je na važnost ranog prepoznavanja bolesti, individualizirani pristup liječenju i interdisciplinarnu suradnju. Istraživanja ukazuju i na povezanost autoimunog tireoiditisa s drugim autoimunim i onkološkim poremećajima, što zahtijeva kontinuirano praćenje bolesnika. Unatoč znatnom napretku, brojna pitanja o patogenezi i razvoju bolesti još uvijek ostaju otvorena.Autoimmune thyroiditis is the most common autoimmune disease in humans and includes two main clinical entities – Hashimoto’s thyroiditis (HT) and Graves’ disease (GD). These are organ-specific disorders characterized by lymphocytic infiltration and the presence of autoantibodies directed against specific components of thyrocytes. While HT leads to hypothyroidism due to the destruction of glandular parenchyma, GD causes hyperthyroidism triggered by stimulating antibodies to the TSH receptor. Diagnosis is based on laboratory tests, ultrasound, and thyroid scintigraphy. The pathogenesis of autoimmune thyroiditis involves a complex interaction of genetic predispositions (HLA, CTLA-4), environmental factors (smoking, iodine intake), and dysfunction of immune surveillance, especially T lymphocytes and natural killer (NK) cells. The clinical presentation is dominated by nonspecific symptoms – anxiety, fatigue, changes in body weight – which complicates timely diagnosis. Therapeutic approaches include pharmacological treatment (antithyroid drugs, levothyroxine), radioiodine therapy, and thyroidectomy, depending on the disease phenotype. Special emphasis is placed on the importance of early disease recognition, individualized treatment approaches, and interdisciplinary cooperation. Research also indicates an association between autoimmune thyroiditis and other autoimmune and oncological disorders, which requires continuous patient monitoring. Despite significant progress, many questions regarding the pathogenesis and development of the disease still remain unanswered
The impact of treatment burden with intravitreal injections on treatment outcomes
No full textIntravitrealna terapija anti-VEGF lijekovima predstavlja temeljni pristup u liječenju bolesti stražnjeg segmenta oka, osobito neovaskularne senilne makularne degeneracije (nAMD), dijabetičkog makularnog edema (DME) i okluzije retinalne vene (RVO). Iako klinička ispitivanja potvrđuju visoku učinkovitost ove terapije u očuvanju i poboljšanju vidne oštrine, stvarni ishodi u svakodnevnoj praksi često su slabiji zbog prisutnosti terapijskog preopterećenja. Terapijsko preopterećenje obuhvaća fizičke, psihološke i organizacijske čimbenike koji utječu na adherenciju pacijenata i dostupnost liječenja. Česti dolasci u bolnicu, invazivnost zahvata, emocionalni stres, kao i ograničeni kapaciteti zdravstvenog sustava, mogu dovesti do propuštanja termina i smanjenja učinkovitosti terapije. Rizik od trajnog gubitka vida povećava se kod pacijenata koji primaju manje od preporučenog broja injekcija godišnje. U svrhu ublažavanja ovih izazova, razvijaju se nove terapijske strategije, uključujući dugodjelujuće lijekove, sustave za produljeno otpuštanje, kombiniranu inhibiciju VEGF-A i Ang-2 te individualizirane protokole liječenja poput „treat-and-extend“ modela. Uz to, važno je poboljšati organizaciju zdravstvenih usluga kroz telemedicinu i ostale tehnološke inovacije, edukaciju pacijenata te osnivanje specijaliziranih zdravstvenih jedinica za primjenu terapije. Cilj ovog rada je analizirati utjecaj terapijskog preopterećenja na ishod liječenja intravitrealnim injekcijama te prikazati suvremene pristupe koji omogućuju održavanje terapijske učinkovitosti uz smanjenje opterećenja za pacijente i zdravstveni sustav.Intravitreal anti-VEGF therapy represents a fundamental approach in the treatment of posterior segment eye diseases, particularly neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Although clinical trials confirm the high efficacy of this therapy in preserving and improving visual acuity, real-world outcomes are often inferior due to the presence of treatment burden. Treatment burden encompasses physical, psychological, and organizational factors that affect patient adherence and access to care. Frequent hospital visits, the invasive nature of the procedure, emotional stress, as well as limited healthcare system capacities, can lead to missed appointments and reduced treatment effectiveness. The risk of permanent vision loss increases in patients receiving fewer than the recommended number of injections per year. To mitigate these challenges, new therapeutic strategies are being developed, including long-acting drugs, sustained-release delivery systems, combined inhibition of VEGF-A and Ang-2 and individualized treatment protocols such as the “treat-and-extend” model. Additionally, improving healthcare service organization through telemedicine, patient education, and specialized clinics is crucial. The aim of this paper is to analyze the impact of treatment burden on the outcomes of intravitreal injection therapy and to present contemporary approaches that enable maintaining therapeutic efficacy while reducing the burden on patients and the healthcare system
The Relationship Between the Modulation of Intestinal Microbiota and the Response to Immunotherapy in Patients with Cancer
No full textThe intestinal microbiota is an important part of the human body, and its composition can affect the effectiveness of immunotherapy. In the last few years, the modulation of intestinal microbiota in order to improve the effectiveness of immunotherapy has become a current topic in the scientific community, but there is a lack of research in this area. In this review, the goal was to analyze the current relevant literature related to the modulation of intestinal microbiota and the effectiveness of immunotherapy in the treatment of cancer. The effects of antibiotics, probiotics, diet, and fecal microbial transplantation were analyzed separately. It was concluded that the use of antibiotics, especially broad-spectrum types or larger quantities, causes dysbiosis of the intestinal microbiota, which can reduce the effectiveness of immunotherapy. While dysbiosis could be repaired by probiotics and thus improve the effectiveness of immunotherapy, the use of commercial probiotics without evidence of intestinal dysbiosis has not yet been sufficiently tested to confirm its safety for cancer for immunotherapy-treated cancer patients. A diet consisting of sufficient amounts of fiber, as well as a diet with higher salt content positively correlates with the success of immunotherapy. Fecal transplantation is a safe and realistic adjuvant option for the treatment of cancer patients with immunotherapy, but more clinical trials are necessary. Modulating the microbiota composition indeed changes the effectiveness of immunotherapy, but in the future, more human studies should be organized to precisely determine the types and procedures of microbiota modulation
Tehnologija i kontrola kakvoće hrane životinjskog podrijetla : priručnik za vježbe
No full textTehnologija i kontrola kakvoće hrane životinjskog podrijetla obvezni je predmet na prvoj
godini Sveučilišnog diplomskog studija sanitarnog inženjerstva, a ovaj je priručnik dio
obvezne ispitne literature za taj predmet.
Cilj predmeta je da student usvoji znanja i vještine potrebne za stručnu komunikaciju o
pitanjima dobre proizvodne i dobre higijenske prakse sa strukama izravno uključenim u
poslovanje s hranom životinjskog podrijetla.
Priručnikom je obuhvaćeno 30 sati organizirane vježbovne nastave, od čega 58 % čini
laboratorijski rad (senzorske i fizikalno-kemijske analize), a ostalo su pogonske vježbe
(terenska nastava) i vježbe iz analize sadržaja deklaracije proizvoda. Hrana životinjskog
podrijetla predstavljena je s nekoliko odabranih primjera proizvoda i njihovih analitičkih
parametara.
Svaka od 10 vježbi u svom uvodnom dijelu sadrži teorijske postavke kojima se studenta
upućuje na karakter analitičkog postupka, značenje informacija koje iz njega proizlaze te
primjenu u praksi. Navođenjem ishoda učenja studenta se usmjerava na ono što treba imati
u fokusu tijekom pripremanja i provođenja vježbe te tijekom pripreme za provjeru usvojenih
znanja i vještina. U tom su kontekstu osmišljeni i zadatci za samostalno vježbanje i
samoprovjeru znanja koji se nalaze na kraju svake vježbe. Rješenja ovih zadataka nisu
navedena u priručniku zbog namjere da student ispravnost svojih odgovora i načina
rješavanja zadataka provjeri u izravnim konzultacijama s nastavnicima.
Olivera Koprivnja
Targeted Therapy for the Treatment of Metastatic Non-Small-Cell Lung Cancer with ALK Gene Rearrangement
No full textKarcinomi pluća nemalih stanica obuhvaćaju oko 85 % od ukupnog broja karcinoma pluća. Napretkom dijagnostike dokazane su određene mutacije na temelju kojih se razvija individualiziran pristup liječenju karcinoma pluća. Jedna od tih mutacija, zastupljena u 3-7 % pacijenata, mutacija je kinaze anaplastičnog limfoma (ALK). U liječenju uznapredovanog ALK pozitivnog karcinoma pluća nemalih stanica koriste se tri generacije lijekova. Prvoj generaciji pripada krizotinib, drugoj generaciji alektinib, ceritinib i brigatinib, dok trećoj generaciji pripada lorlatinib. Svi su superiorni u odnosu na dosadašnje tradicionalno liječenje kemoterapijom. Najsuperiorniji od svih je lorlatinib koji pripada skupini treće generacije jer je još uvijek osjetljiv na rezistentne mutacije te najbolje prodire kroz krvno-moždanu barijeru. Cilj je ovog preglednog članka usporediti učinkovitost, sigurnost i mehanizme djelovanja te nuspojave navedenih lijekova. Ne može se porgiješiti odabirom bilo kojeg inhibitora kinaze anaplastičnog limfoma s obzirom na dobru učinkovitost i sigurnost primjene.Non-small cell lung cancer is represented in 85% of the total number of lung cancers. With the progress of diagnostics, certain mutations have been proven, since an individualized approach to the treatment of lung cancer is being developed. One of these mutations, present in 3-7% of patients, is the anaplastic lymphoma kinase (ALK) mutation. Three generations of drugs are used in the treatment of advanced ALK positive non-small cell lung cancer. Crizotinib belongs to the first generation, alectinib, ceritinib and brigatinib to the second generation, and lorlatinib belongs to the third generation. All of them are superior to traditional chemotherapy treatment. The most superior of all is lorlatinib, which belongs to the third-generation group, because it is still sensitive to resistant mutations and best penetrates the blood-brain barrier. The aim of this review article is to compare the effectiveness, safety, mechanisms of action and side effects of the mentioned drugs
Robot-Assisted Nephrectomy in a Living Kidney Donor – a Case Report
No full textCilj: Uvođenje minimalno invazivnih metoda u donorsku kirurgiju dovelo je do povećanja broja živih darivatelja bubrega. U današnje se vrijeme laparoskopska donorska nefrektomija smatra zlatnim standardom, no broj se robotski asistiranih donorskih nefrektomija (RADN) povećava. Prikazat ćemo bolesnika u kojega je učinjen RADN i posljedična uspješna transplantacija bubrega. Prikaz slučaja: U 77-godišnjeg bolesnika s adultnom policističnom bolešću bubrega došlo je do progresije u terminalni stadij bubrežnog zatajenja te je u prosincu 2022. započeo s dijalitičkim liječenjem. Nakon opsežne obrade njegova 61-godišnja sestra prihvaćena je kao donor. U rujnu 2023. učinjen je RADN, a odstranjen joj je lijevi bubreg. Slijedila je uspješna transplantacija bubrega, a hladna ishemija trajala je četiri sata i 30 minuta. Poslijeoperacijski tijek bio je uredan u darivatelja i primatelja. Tri mjeseca nakon operacije bubrežna funkcija bila je stabilna u oboje bolesnika. Zaključak: RADN je sigurna i efikasna metoda s podjednakim rezultatima kao i kod laparoskopske donorske nefrektomije, a provodi se u centrima gdje se radi robotska kirurgija.Aim: The use of minimal-invasive surgical methods in kidney donation surgery led to an increased number of living kidney donors. The laparoscopic donor nephrectomy has become the gold standard for living kidney donation but nowadays the robot-assisted nephrectomy for living kidney donation (RADN) has been performed in expert centres. We present a case of RADN followed by a successful kidney transplantation. Case report: The 77-year-old man with adult polycystic kidney disease gradually progressed to end-stage renal disease and started with dialysis in December 2022. After extensive assessment, his 61-year-old sister was prepared to be a donor. In September 2023, a successful RADN was performed. The left kidney was procured. The kidney was successfully transplanted to the recipient with a cold ischemia time of 4 hours and 30 minutes. The postoperative course was uneventful for both donor and recipient. Three months after surgery the renal function is stable in both patients. Conclusion: The RADN is a safe and effective method with comparable results to laparoscopic donor nephrectomy used in centres with robotic surgery
In Silico Validation of OncoOrigin: An Integrative AI Tool for Primary Cancer Site Prediction with Graphical User Interface to Facilitate Clinical Application
No full textCancers of unknown primary (CUPs) represent a significant diagnostic and therapeutic challenge in the field of oncology. Due to the limitations of current diagnostic tools in these cases, novel approaches must be brought forward to improve treatment outcomes for these patients. The objective of this study was to develop a machine-learning-based software for primary cancer site prediction (OncoOrigin), based on genetic data acquired from tumor DNA sequencing. By design, this was an in silico diagnostic study, conducted using data from the cBioPortal database (accessed on 21 September 2024) and several data processing and machine learning Python libraries. The study involved over 20,000 tumor samples with information on patient age, sex, and the presence of genetic variants in over 600 genes. The main outcome of interest was machine-learning-based discrimination between cancer site classes. Model quality was assessed by training set cross-validation and evaluation on a segregated test set. Finally, the optimal model was incorporated with a graphical user interface into the OncoOrigin software. Feature importance for class discrimination was also determined on the optimal model. Out of the four tested machine learning estimators, the XGBoostClassifier-based model proved superior in test set evaluation, with a top-2 accuracy of 0.91 and ROC-AUC of 0.97. Unlike other machine learning models published in the literature, OncoOrigin stands out as the only one integrated with a graphical user interface, which is crucial for facilitating its use by oncology specialists in everyday clinical practice, where its application and implementation will have the greatest value in the future
Depth Perception and Intraocular Differences in Visual Acuities Among Older Spectacle Wearers
No full textBackground: Falls impose a heavy financial burden on society, and the incidence is age-related. The correction of refractive errors has been mooted as a valuable procedure to prevent falls. However, depth perception, estimated by stereo acuity tests, is reduced in the older population and has been cited as contributing to the higher incidence of falls in the elderly. Objective: To explore the clinical relationship between age, interocular differences in the corrected distance and near logMAR visual acuities, refractive errors, axial (eyeball) lengths, pupil sizes, and higher-order ocular aberrations (HOAs) on clinical measures of stereoacuity and aniseikonia in asymptomatic presbyopic habitual spectacle wearers. Methods: Total amount of 91 subjects underwent clinical assessment of i) subjective refractive error, ii) stereoacuity at 6m and 40cm (Randot Stereotests), iii) aniseikonia at 6m (Awaya test along vertical and horizontal meridian) iv) higher order aberrations (Hartman-Shack aberrometer) v) eyeball length and pupil size (IOL master 700). The Pythagorean theorem was applied to each pair of aniseikonia values to calculate the resultant aniseikonia (AR). Results: Mean (±sd,95%CI) age of the subjects was 56.2years (±8.10,54.6-57.9). Root mean square (RMS) interocular differences (±sd,95%CI) in spherical refractive errors, axial lengths and pupil sizes were 0.66D(±0.93,0.47-0.85), 0.24mm (±0.33,0.17-0.31), 0.15mm (±0.11,0.12-0.17). The median (mode, interquartile range) values for AR were 2.8(1.0,1.3-4.0). Significant correlations (