Veterinary medicine - Repository of PHD, master's thesis
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Osteoarthritis of the knee
No full textOsteoartritis koljena (KOA) predstavlja najčešći oblik osteoartritisa i jedan od vodećih uzroka kronične boli, invaliditeta i smanjenja kvalitete života kod odraslih osoba. Prevalencija KOA raste s dobi, pretilošću i pojavom traume ili ponavljanih mikrotrauma zgloba, a zahvaća sve strukture koljena — hijalinsku hrskavicu, subhondralnu kost, sinoviju, kapsulu, ligamente i periartikularne mišiće. Patogeneza bolesti je multifaktorialna: mehaničko preopterećenje i promjene u izvanstaničnoj matrici hrskavice (povećana ekspresija MMP i ADAMTS enzima, gubitak proteoglikana i kolagena tipa II) odvode u hondromalaciju i progresivni gubitak hrskavice, dok upalne citokine (IL-1, TNF-α, IL-6 i dr.) pojačavaju degradaciju i sinovitis. Klinička slika KOA uključuje bol pri opterećenju, jutarnju ukočenost (do 30 minuta), ograničenje fleksije i/ili ekstenzije, krepitacije te slabost kvadricepsa. Fizikalni pregled i anamneza usmjereni su na procjenu lokalizacije boli, mehaničkih simptoma i funkcionalnog statusa. Standardne antero-posteriorne radiografije u opterećenju dovoljno su pouzdane za dijagnosticiranje suženja zglobnog prostora, osteofita i subhondralne skleroze, dok MRI i ultrazvuk doprinose ranom otkrivanju promjena na hrskavici i sinovijalnoj membrani.
Terapija KOA temelji se na kombinaciji nefarmakoloških i farmakoloških mjera, uz individualizirani plan liječenja. Temelji konzervativne terapije su edukacija o bolesti, gubitak težine, program vježbi (aerobne, vježbe snage, neuromuskularne) i ortopedska pomagala, koje smanjuju opterećenje i poboljšavaju mišićnu potporu zgloba. Farmakološki pristup obuhvaća analgetike (paracetamol), NSAID-e (oralno i topikalno), te intraartikularne injekcije kortikosteroida ili hijaluronske kiseline. Regenerativne metode (PRP, matične stanice) pokazuju obećavajuće rezultate, ali zahtijevaju dodatna istraživanja. Kod uznapredovalih slučajeva indicirani su kirurški zahvati: osteotomije za preraspodjelu opterećenja i djelomične ili totalne artroplastike koljena. Unikondilarna i patelofemoralna artroplastika prikladne su za ograničene zahvaćene dijelove, dok totalna artroplastika ostaje zlatni standard u difuznom KOA. Nadalje, artroskopija je rezervirana za specifične indikacije (traumatske meniskalne lezije, mehanička blokada, septični artritis).
S obzirom na epidemiološki rast i značajan socioekonomski teret, ključne su prevencija (rani zahvati na modifikatornim čimbenicima), rana dijagnostika i multidisciplinarni pristup. Daljnja istraživanja usmjerena su na razumijevanje molekularnih mehanizama i razvoj novih terapijskih modaliteta koji bi, u kombinaciji s postojećim standardima, omogućili bolje ishode liječenja i očuvanje funkcije koljena.Knee osteoarthritis (KOA) is the most common form of osteoarthritis and one of the leading causes of chronic pain, disability, and reduced quality of life in the adult population. The prevalence of KOA increases with age, obesity, and joint trauma or repetitive microtrauma. The disease affects all knee structures—hyaline cartilage, subchondral bone, synovium, capsule, ligaments, and periarticular muscles. The pathogenesis is multifactorial: mechanical overload and alterations in the extracellular matrix of the cartilage (increased expression of MMP and ADAMTS enzymes, loss of proteoglycans and type II collagen) lead to chondromalacia and progressive cartilage loss, while inflammatory cytokines (IL-1, TNF-α, IL-6, etc.) amplify degradation and contribute to synovitis. Clinically, KOA presents with load-induced pain, morning stiffness (lasting up to 30 minutes), reduced range of motion, crepitus, and quadriceps weakness. Physical examination and medical history focus on pain localization, mechanical symptoms, and functional status. Standard anteroposterior weight-bearing radiographs are sufficient for diagnosing joint space narrowing, osteophytes, and subchondral sclerosis. MRI and ultrasound provide greater sensitivity in detecting early cartilage and synovial changes.
Treatment is based on a combination of non-pharmacological and pharmacological approaches, tailored to the individual patient. Core conservative therapies include patient education, weight loss, structured exercise programs (aerobic, strength, neuromuscular), and orthopedic aids to reduce load and enhance joint support. Pharmacological management includes analgesics (paracetamol), NSAIDs (oral and topical), and intra-articular injections of corticosteroids or hyaluronic acid. Regenerative therapies (PRP, stem cells) show promising results but require further research. In advanced stages, surgical interventions are indicated: osteotomies to redistribute load and partial or total knee arthroplasty. Unicompartmental and patellofemoral arthroplasty are suitable for localized joint damage, while total knee replacement remains the gold standard for diffuse KOA. Arthroscopy is reserved for specific indications such as traumatic meniscal tears, mechanical joint block, or septic arthritis.
Given its growing prevalence and significant socioeconomic burden, KOA requires early intervention focused on modifiable risk factors, prompt diagnosis, and a multidisciplinary treatment approach. Future research should aim to further clarify the molecular mechanisms of disease progression and develop innovative therapeutic options that, in combination with current standards, could improve outcomes and preserve joint function
Breaking the Cycle: Enhancing Cardiovascular Health in the Elderly Through Group Exercise
No full textThe global increase in aging populations underscores the urgency of addressing cardio–kidney metabolic health indicators, particularly among sedentary elderly individuals. This study investigates the impact of an 8-month structured group exercise program on cardiovascular health indicators among 320 women aged 60 and older living independently in Rijeka. Participants engaged in biweekly sessions designed to improve mobility, balance, and strength. Key metrics, including blood pressure (BP), body mass index (BMI), waist-to-hip (WHR) and waist-to-height ratio (WHtR), and hand grip strength, were measured before and after the intervention. Results revealed significant reductions in systolic blood pressure (mean −3.4 mmHg) and pulse pressure among hypertensive participants, highlighting improved cardiovascular function. BP control significantly improved (7.2%), and 19% of untreated hypertensive subjects at the start become normotensive at the end of follow-up. Although BMI changes were minimal, WHtR improvements indicated reductions in central obesity and muscle fat redistribution. Hand grip strength increased significantly on both arms, correlating with physical capacity. The results underline the benefits of group training for improving health even in the elderly population through an organized exercise program. While these preliminary results demonstrate promising health improvements, further research with longer follow-up and inclusion of diverse participant groups is recommended to validate these outcomes and refine intervention strategies
Otkrivanje neurorazvojne osnove Downovog sindroma pomoću jedinstvenih organoida ljudskog mozga: plan upravljanja istraživačkim podacima
No full textCan we rely on single use bronchoscopes in central airway obstruction management? A preliminary, open label randomised controlled trial
No full textMolecular diversity among adult hippocampal and entorhinal cells
No full textThe hippocampal system is a critical component in cognition, adult neurogenesis, and selectively sensitive to aging and neurodegenerative processes. To gain insights into neurogenic potential and diversity of cell types in adult humans, we profiled single-nucleus transcriptomes in five hippocampal subregions. Integration of dentate gyrus data with mouse, pig and macaque, showed strong neurogenesis trajectories in these species that was absent in humans. Doublecortin (DCX), the common marker of neurogenesis in the dentate gyrus, showed widespread expression in the human hippocampal system, including some mature
dentate granule cells, but did not define immature cell populations in humans. We further revealed prominent diversity among excitatory neurons across the hippocampal system that echoed the transition from three-layered archicortex to six-layered neocortex. Our results highlighted the uncharacterized METTL7B associated with Alzheimer’s disease-related proteins and enriched in primates in neuronal subtypes and subregions more resilient to early neuropathological changes in the Alzheimer’s disease. Overall, our findings unveiled cell typespecific molecular characteristics pertinent to hippocampal physiological function.Neuralni krugovi hipokampalne (HIP) i entorinalne moždane kore (EC) ključni su dijelovi široke neuronske mreže odgovorne za pamćenje te reprezentaciju prostora i vremena. U svrhu boljeg uvida u pojedinačne neuronske i ne-neuronske populacije tog sustava, provedeno je RNA sekvencioniranje pojedinačnih staničnih jezgara (snRNA-seq) uzoraka iz pet anatomski definiranih podregija hipokampalnog sustava. Integrirana analiza između vrsta pokazala je transkriptomske i histološke znakove neurogeneze u odraslim miševima, svinjama i makaki majmunima, ali ne i u ljudi. DCX, marker novonastalih zrnatih stanica, pronađen je u različitim neuronskim populacijama odraslog čovjeka, ali nije definirao populacije nezrelih neurona. Također, opisali smo specifične, subregionalno transkriptomski definirane tipove stanica i promjene u prijelazu iz troslojnog arhikorteksa u šestoslojni neokorteks. Naši rezultati istaknuli su da je METTL7B povezan s proteinima povezanim s Alzheimerovom bolešću i obogaćen u primata u podtipovima stanica i podregijama otpornijim na rane neuropatološke promjene u Alzheimerovoj bolesti. Ovo istraživanje je otkrilo molekularne karakteristike određenih vrsta i podtipova stanica koje potencijalno imaju važnu ulogu u fiziološkoj funkciji i/ili patološkim promjenama hipokampalnog sustava
Testicular tissue bank: ten years of testicular tissue cryopreservation in Croatia
No full textThe Testicular Tissue Bank has been operating at the University Hospital Center (UHC) Zagreb since 2013. It aims to cryopreserve testicular tissue from patients with azoospermia. If spermatozoa are found in the collected tissue, a combined procedure known as testicular sperm extraction (TESE)/intracytoplasmic sperm injection (ICSI) is performed. During the last 10 years, our bank has deposited samples from 443 patients collected either by conventional TESE or microsurgical TESE procedure. Among them, 9% were from oncological patients whose samples were stored to preserve fertility. According to pathohistological analysis, 17% of patients were diagnosed with complete spermatogenesis or hypospermatogenesis, 11% with spermatogenic arrest, 48% with mixed atrophy of seminiferous tubules, and 24% with Sertoli cell-only phenotype or tubular fibrosis. Overall, the presence of testicular spermatozoa was found in 58% of patients, which makes them suitable for the ICSI procedure. In 21 out of 59 patients (36%) who underwent a salvage TESE, the outcome was different than that of the first spermatozoa retrieval attempt. Considering that the male factor is one of the leading causes of infertility, the results of Testicular Tissue Bank activity confirm its important role in improving the demographic picture of Croatia
Characterization of immune microenvironment based on PD-L1 expression in molecular subtypes of muscle-invasive bladder cancer
No full textMišićno-invazivni karcinom mokraćnog mjehura (engl. muscle-invasive bladder cancer, MIBC) je agresivna bolest koja zahtijeva multimodalni pristup liječenju. Dobro je poznata morfološka i molekularna heterogenost tumora, a što se očituje u različitosti molekularnog profila i ponašanja. Dva su osnovna molekularna tipa karcinoma mokraćnog mjehura luminalni i bazalni. Pojedini tipovi pokazuju različite odgovore na terapiju, a smatra se i da je odgovor na nove oblike liječenja poput imunoterapije različit. Imunoterapija je novost u liječenju MIBC te aktivira antitumorski imunitet. U ovom radu istražena je izraženost biomarkera PD-L1 u luminalnom i bazalnom tipu MIBC. Temeljem „nasumičnog“ odabira 40 uzorka materijala bolesnika s postavljenom dijagnozom urotelnog karcinoma,najmanje pT2 stadija, dobivenog transuretralnom resekcijom izdvojeni su luminalni i bazalni tip MIBC. Fenotipizacija je učinjena imunohistokemijskom analizom dva temeljna markera ( Citokeratin 5/6 i GATA3). Luminalni tumori pokazali su niži izražaj PD-L1 (prosječna pozitivnost 2%), dok je kod bazalnog tipa ona iznosila 18%. Također je utvrđen porast udjela pozitivnih stromalnih limfocita u tumora s izražajem CK 5/6. Rezultat ovog istraživanja unaprjeđuje razumijevanje imunološkog konteksta MIBC što potencijalno doprinosi lakšoj selekciji podskupine pacijenata koja bi mogla imati korist od imunoterapije.Muscle-invasive bladder cancer (MIBC) is an aggressive disease that requires a multimodal approach to treatment. These tumors are well known for their morphological and molecular heterogeneity, which is reflected in the diversity of the molecular profile and behavior. There are two basic molecular types of bladder cancer, luminal and basal. The types show different responses to therapy, and it is believed that the response to new forms of treatment such as immunotherapy is different. Immunotherapy is a new treatment for MIBC and activates antitumor immunity. This paper investigated the expression of the PD-L1 biomarker in luminal and basal type MIBC. Based on a "random" selection of 40 material samples of patients with a given diagnosis of urothelial carcinoma with the lowest stage of pT2, obtained by transurethral resection were isolated luminal and basal type MIBC. Phenotyping was done by immunohistochemical analysis of twobasic markers (Cytokeratin 5/6 and GATA3). Luminal tumors showed lower expression of PD-L1 (average positivity 2%), while in the basal type it was 18%. An increase was also found in the proportion of positive stromal lymphocytes in tumors with CK 5/6 expression. The result of this research advances the understanding of the immune context of MIBC as potentially contributes to the easier selection of a subgroup of patients who could benefit from immunotherapy
Femoral stem types in total hip arthroplasty
No full textTotalna endoproteza (TEP) kuka je učinkovita metoda za liječenje uznapredovalih bolesti kuka, osobito kada konzervativna terapija više ne daje zadovoljavajuće rezultate. Razvoj ove kirurške tehnike ima bogatu povijest, s ključnim iskorakom sredinom 20. stoljeća, kada je Sir John Charnley izveo prvu cementiranu TEP kuka. Od tada, kontinuirana tehnološka i biomehanička unaprjeđenja dovela su do današnjih sofisticiranih implantata i kirurških metoda. Femoralne komponente TEP kuka dijele se na dvije vrste: cementne i bescementne. Cementne femoralne komponente koriste kombinaciju kosti i polimetilmetakrilatnog cementa za osiguranje stabilnosti implantata. Klasifikacija cementnih femoralnih komponenti temelji se na mehanizmu fiksacije implantata, pri čemu se razlikuju dva osnovna koncepta: fiksacija kompozitnom gredom i konusno klizna fiksacija. Ove metode razlikuju se prema načinu prijenosa opterećenja s endoproteze na kost te prema načinu postizanja primarne stabilnosti implantata. Nasuprot njima, bescementne femoralne komponente oslanjaju se na biološku fiksaciju putem osteointegracije na poroznu i hrapavu površinu implantata. Suvremene klasifikacije dijele bescementne femoralne implantate prema dizajnu, modularnosti i duljini, te s obzirom na biomehaničke aspekte i površinsku obradu. Radiološka analiza ima ključnu ulogu u planiranju zahvata i praćenju poslije operativnog statusa. Cementne femoralne komponente pretežno se primjenjuju kod starijih pacijenata s reduciranom kvalitetom kosti, dok se bescementni implantati preferiraju kod mlađih i aktivnijih bolesnika zbog bolje osteointegracije. Uz pažljiv odabir, bescementne endoproteze mogu se uspješno koristiti i kod starije populacije. Dugoročni ishodi obje metode fiksacije pokazuju visoku učinkovitost, uz izbor tipa implantata koji se prilagođava individualnim karakteristikama pacijenta.Total hip arthroplasty (THA) is an effective treatment method for advanced hip diseases, particularly when conservative therapy no longer yields satisfactory results. The development of this surgical technique has a rich history, with a key breakthrough in the middle of the 20th century, when Sir John Charnley performed the first cemented THA. Since then, continuous technological and biomechanical advancements have led to today’s sophisticated implants and surgical methods. Femoral components of THA are divided into two types: cemented and cementless. Cemented femoral components use a combination of bone and polymethylmethacrylate cement to ensure implant stability. Classification of cemented femoral components is based on the mechanism of fixation of the implant, with two basic concepts distinguished: composite beam and taper slip fixation. These methods differ in the way of load transfer from the prosthesis to the bone and in the way of achieving primary stability of the implant. In contrast, cementless femoral components rely on biological fixation through osteointegration on the porous and rough surface of the implant. Modern classifications divide cementless femoral implants according to design, modularity, and length, as well as according to biomechanical aspects and surface treatment. Radiological analysis plays a key role in planning the procedure and monitoring postoperative status. Cemented femoral components are predominantly used in older patients with reduced bone quality, while cementless implants are preferred in younger and more active patients due to better osteointegration. With careful selection, cementless prostheses can also be successfully used in the older population. Long-term outcomes of both fixation methods show high effectiveness, with the choice of implant type adapted to the individual characteristics of the patient
Red blood cell distribution width (RDW) as a predictor of thrombotic events in patients with myelofibrosis
No full textKronične mijeloproliferativne neoplazme (MPN) skupina su bolesti koje nastaju zbog hiperprodukcije i nakupljanja stanica jedne ili više mijeloidnih loza. Među njima se izdvajaju Philadelphia negativne MPN: policitemija vera, esencijalna trombocitemija i primarna mijelofibroza. Glavne mutacije koje nalazimo u bolesnika s Philadelphia negativnim MPN su u JAK2, CALR i MPL genima. U bolesnika s mijelofibrozom dominira rizik smrti uslijed progresije bolesti, međutim u njih postoji i visok trombotski rizik. Bolesnici s mijelofibrozom također karkateristično imaju vrlo visoke vrijednosti širine distribucije eritrocita (RDW), laboratorijskog parametra koji kvantificira anizocitozu i za koji je poznato kako je povezan s povećanim trombotskim rizikom u općoj populaciji. Hipoteza ovog istraživanja bila je kako bolesnici s mijelofibrozom i izraženijom anizocitozom mjereno kroz RDW imaju veću sklonost trombotskim incidentima.
Retrospektivno smo analizirali kohortu od 144 bolesnika s primarnom ili sekundarnom mijelofibrozom koji su dijagnosticirani ili praćeni u Kliničkoj bolnici Dubrava u periodu od 2004. do 2024. godine. Analizirali smo vrijednosti RDW prilikom dijagnoze, povezanost s kliničkim karakteristikama i s trombotskim rizikom u praćenju.
Prilikom dijagnoze bolesnici s mijelofibrozom imali su medijan vrijednosti RDW-a 19.3%. Vrijednosti RDW-a u u prosjeku nisu pokazivale statistički značajnu dinamiku tijekom vremena, te korištenje pojedinih citoreduktivnih lijekova nije značajno utjecalo na promjenu RDW tijekom vremena. Viši RDW bio je statistički značajno povezan sa ženskim spolom, odsustvom mutacija CALR gena, višim stupnjem fibroze koštane srži, anemijom i trombocitopenijom, prisutnošću konstitucijskim simptoma, ovisnošću o transfuziji eritrocita, većom palpatornom većinom slezene, višim DIPSS skorom rizika za smrt i višim Charlsonovim indeksom komorbiditeta.
Više vrijednosti RDW bile su povezane s povećanim trombotskim rizikom za tromboze općenito (18% većim rizikom sa svaki postotni bod porasta vrijednosti RDW) i za pojavu venskih tromboza. Porast RDW-a tijekom 6 mjeseci bio je povezan s povećanim rizikom od arterijske tromboze.
Ovo istraživanje pokazuje ulogu RDW-a kao široko dostupnog i jeftinog prognostičkog alata za predviđanje trombotskih incidenata u bolesnika s mijelofibrozom, a rezultate je potrebno validirati na većem uzorku i u prospektivnim uvjetima istraživanja.Chronic myeloproliferative neoplasms (MPN) are a group of neoplastic diseases caused by the hyperproduction and accumulation of cells from one or more myeloid lineages. Among these, Philadelphia-negative MPNs include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. The main mutations found in patients with Philadelphia-negative MPNs are in the JAK2, CALR, and MPL genes. In patients with myelofibrosis, the risk of death due to disease progression is dominant, but these patients also have a high thrombotic risk. Patients with myelofibrosis also characteristically have very high values of red cell distribution width (RDW), a laboratory parameter that quantifies anisocytosis and is known to be associated with an increased thrombotic risk in the general population. The hypothesis of this study was that patients with myelofibrosis and more pronounced anisocytosis, as measured by RDW, have a greater tendency toward thrombotic incidents.
We retrospectively analyzed a cohort of 144 patients with primary or secondary myelofibrosis who were diagnosed or followed at University Hospital Dubrava in the period from 2004 to 2024. We analyzed RDW values at diagnosis, their association with clinical characteristics, and with thrombotic risk during follow-up.
At diagnosis, patients with myelofibrosis had a median RDW value of 19.3%. On average, RDW values did not show statistically significant changes over time, and the use of certain cytoreductive drugs did not significantly affect RDW change over time. Higher RDW was statistically significantly associated with female sex, absence of CALR gene mutations, higher degree of bone marrow fibrosis, anemia and thrombocytopenia, presence of constitutional symptoms, dependence on red blood cell transfusions, larger palpable spleen size, higher DIPSS risk score for death, and higher Charlson comorbidity index.
Higher RDW values were associated with an increased thrombotic risk in general (an 18% higher thrombotic risk for each percentage point increase in RDW) and with the occurrence of venous thrombosis. An increase in RDW over six months was associated with an increased risk of arterial thrombosis.
This study demonstrates the role of RDW as a widely available and inexpensive prognostic tool for predicting thrombotic incidents in patients with myelofibrosis, but the results need to be validated in a larger sample and under prospective research conditions
Reconstruction of the lower extremity using free flaps
No full textZahvaljujući razvoju mikrokiruške tehnike slobodni režnjevi postali su zlatni standard u liječenju velikih defekata donjeg ekstremiteta. Defekti koji zahtijevaju takvu vrstu rekonstruktivnih zahvata često su posljedica djelovanja sila visokih energija pri čemu
dolazi do ozljede mekotkivnih struktura i kosti, ali i defekti nastali nakon zračenja, otklanjana tumora te kroničnih rana. Primjena slobodnih režnjeva ima puno bolje funkcionalne i estetske rezultate u odnosu na konvencionalne metode, što je izuzetno
bitno kada je riječ o liječenju trauma donjih ekstremiteta. Ključnu ulogu igra pravilna procjena i klasifikacija ozljede, individualni pristup svakom pacijentu te uigranost multidisciplinarnog tima koje ovakve ozljede nerijetko zahtijevaju. Najčešće
primjenjivani slobodni režnjevi su anterolateralni bedreni i latissimus dorsi režanj. Svaki od njih odlikuje se svojim prednostima i manama, ali njihova kvaliteta nadilazi njihove nedostatke zbog čega često predstavljaju prvi izbor u rekonstruktivnoj kirurgiji.With the advancement of microsurgical techniques, free flaps have become the gold standard reconstructing complex lower extremity defects. Such defects are most commonly caused by high-energy trauma resulting in damage to both soft tissues and bone. Still, they may also arise after radiation therapy, tumor resection, or as a consequence of chronic wounds. Compared to conventional methods, free flaps offer superior functional and aesthetic outcomes - an especially important consideration in the management of lower limb injuries. Successful reconstruction relies heavily on accurate injury assessment, proper classification, an individualized approach tailored to each patient and well coordinated multidisciplinary team. The most frequently used free flaps are the anterolateral thigh flap (ALT) and the latissimus dorsi flap (LD). Each
has distinct advantages and disadvantages; however, their overall reliability and versatility often make them the preferred choice in reconstructive surgery