Veterinary medicine - Repository of PHD, master's thesis
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Recurrence of hepatocellular carcinoma after liver transplantation
No full textTransplantacija jetre predstavlja kurativnu opciju za hepatocelularni karcinom (HCC), no recidiv bolesti i dalje se javlja u 8–20 % bolesnika, osobito u uvjetima trajne imunosupresije. Glavni rizični čimbenici uključuju mikrovaskularnu i makrovaskularnu invaziju, visoko tumorsko opterećenje, povišeni alfa-fetoprotein, transplantaciju izvan prihvaćenih kriterija i nedovoljan odgovor na prethodnu terapiju. Novija istraživanja ukazuju i na potencijalnu ulogu metaboličkih poremećaja u nastanku recidiva.
U ovom diplomskom radu provedeno je retrospektivno istraživanje na 231 bolesniku transplantiranom zbog HCC-a u KB Merkur (2016.–2024.). Analizirani su klinički, laboratorijski i patohistološki podaci, uključujući primjenu TACE terapije i razine takrolimusa. Recidiv je zabilježen kod 10,39 % bolesnika. Statistički značajna povezanost s recidivom utvrđena je za veći broj tumorskih čvorova, prisutnost mikrovaskularne i limfovaskularne invazije te viši stadij bolesti. Također, zabilježena je veća učestalost hiperlipoproteinemije u skupini s recidivom, što može upućivati na metaboličku komponentu rizika.
Zaključno, broj tumorskih čvorova i mikrovaskularna invazija potvrđeni su kao ključni čimbenici rizika za recidiv HCC-a, dok metabolički poremećaji mogu dodatno doprinijeti procjeni rizika. Potrebna su daljnja prospektivna istraživanja za precizniju stratifikaciju bolesnika nakon transplantacije.Liver transplantation represents a curative treatment option for hepatocellular carcinoma (HCC), but disease recurrence still occurs in 8–20% of patients, particularly in the context of lifelong immunosuppression. Major risk factors include microvascular and macrovascular invasion, high tumor burden, elevated alpha-fetoprotein levels, transplantation beyond accepted criteria, and inadequate response to downstaging therapies. Recent studies also suggest a potential role of metabolic disorders in increasing the risk of recurrence.
This thesis presents a retrospective study of 231 patients who underwent liver transplantation for HCC at Merkur University Hospital between 2016 and 2024. Clinical, laboratory, and histopathological data were analyzed, including the use of TACE therapy and tacrolimus levels. Disease recurrence was observed in 10.39% of patients. Statistically significant associations with recurrence were found for a higher number of tumor nodules, the presence of microvascular and lymphovascular invasion, and more advanced tumor stage. Additionally, hyperlipoproteinemia was more frequent in the recurrence group, indicating a possible metabolic contribution to recurrence risk.
In conclusion, the number of tumor nodules and microvascular invasion were confirmed as key risk factors for HCC recurrence, while metabolic factors such as hyperlipoproteinemia may have additional prognostic value. Further prospective studies are needed to improve risk stratification after liver transplantation
The Impact of Blood Transfusion on Postoperative Inflammatory Marker Elevation and Empirical Antibiotic Therapy Following Aortic Valve Replacement
No full textCilj ovog rada bio je usporediti vrijednosti upalnih parametara i učestalost empirijske primjene antibiotika između skupine transfundiranih i netransfundiranih bolesnika nakon zamjene aortnog zaliska. Provedeno je retrospektivno opservacijsko kohortno istraživanje u kojem je proučavana populacija bolesnika podvrgnutih zamjeni aortnog zaliska u periodu od veljače 2023. do siječnja 2025. godine na Zavodu za kardijalnu i transplantacijsku kirurgiju Kliničke bolnice Dubrava. Istraživanje je obuhvatilo 167 pacijenata od kojih je 102 (61,1%) transfundirano i 65 (38,9%) netransfundirano. Nakon statističke obrade podataka pronađene su značajne razlike u kategorijama dobi, spola, bubrežne i srčane funkcije te hitnosti i trajanja operacije. Skupina koja je primila transfuziju krvi bila je statistički značajno starija (p = 0,001), uočen je veći broj žena (p < 0,001) te su zabilježene niže vrijednosti predoperativnog hemoglobina (p < 0,001), hematokrita (p < 0,001) i eGFR-a (p < 0,001). Transfundirani pacijenti imali su bolju predoperativnu ejekcijsku frakciju (p = 0,044), veći broj elektivnih operacija (p = 0,004), kraće trajanje ekstrakorporalne cirkulacije (p < 0,001) te aortalne kleme (p = 0,001). Rezultati ostalih uspoređivanih varijabli nisu pokazali statistički značajnu razliku. Nije utvrđena statistički značajna razlika vrijednosti upalnih parametara i učestalosti empirijske primjene antibiotika između skupine transfundiranih i netransfundiranih. Razlike u skupinama nije bilo ni u učestalosti postoperativnih infekcija – najčešća infekcija koju su pacijenti razvili bila je urinarna (16,7% vs. 16,4%, p = 0,958), dok su ostali tipovi infekcija bili rijetki i bez statističkog značaja.The aim of this study was to compare the levels of inflammatory markers and the incidence of empirical antibiotic use between transfused and non-transfused patients following aortic valve replacement surgery. A retrospective observational cohort study was conducted, analyzing a population of patients who underwent aortic valve replacement between February 2023 and January 2025 at the Department of Cardiac and Transplant Surgery, Dubrava Clinical Hospital. The study included 167 patients, of whom 102 (61.1%) were transfused and 65 (38.9%) were not. After statistical analysis, significant differences were found in age, sex, renal and cardiac function, as well as in the urgency and duration of the operation. The group that received blood transfusions was significantly older (p = 0.001), had a higher proportion of female patients (p < 0.001), and showed lower preoperative hemoglobin (p < 0.001), hematocrit (p < 0.001), and eGFR values (p < 0.001). Transfused patients had better preoperative ejection fraction (p = 0.044), a higher number of elective surgeries (p = 0.004), and shorter durations of extracorporeal circulation (p < 0.001) and aortic clamping (p = 0.001). The results of other compared variables did not show statistically significant differences. No statistically significant differences were found in the levels of inflammatory markers or the frequency of empirical antibiotic use between the transfused and non-transfused groups. There was also no difference in the incidence of postoperative infections—the most common infection was urinary infection (16.7% vs. 16.4%, p = 0.958), while other types were rare and not statistically significant
Non-alcoholic fatty liver disease after liver transplantation
No full textNealkoholna masna bolest jetre (NAFLD) označava stanje karakterizirano nakupljanjem triglicerida u hepatocitima kod osoba koje ne konzumiraju značajne količine alkohola. Predstavlja spektar jetrenih poremećaja usko povezanih s metaboličkim sindromom, a njezin progresivni oblik nealkoholni steatohepatitis (NASH) dovodi do lipotoksičnosti, upalnog oštećenja hepatocita i, u konačnici,razvoja fibroze i ciroze. Posljednjih godina NASH sve češće postaje uzrok terminalnog zatajenja jetre i indikacija za transplantaciju. Nakon transplantacije jetre, NAFLD se može ponovno javiti u bolesnika kod kojih je primarna bolest bila NASH (rekurencija), ali se može razviti i de novo, osobito u prisutnosti čimbenika rizika poput debljine, inzulinske rezistencije, šećerne bolesti tipa 2 te dugotrajne imunosupresivne terapije. Posttransplantacijski NAFLD često je asimptomatski i otkriva se slučajno, a dijagnostički izazovi uključuju ograničenu pouzdanost neinvazivnih metoda u transplantiranih bolesnika. Iako je biopsija jetre i dalje zlatni standard, u praksi se češće koriste neinvazivne tehnike poput elastografije. Terapijski pristup temelji se na nefarmakološkim mjerama, prije svega na redukciji tjelesne mase i kontroli sastavnica metaboličkog sindroma. Prvi lijek specifično namijenjen liječenju NASH-a odobrila je FDA 2024. godine. S obzirom na sve veću prevalenciju NAFLD-a, kako u općoj populaciji tako i među transplantiranim bolesnicima, rana identifikacija, prevencija i redovito praćenje postaju ključni u očuvanju funkcije presađene jetre i dugoročnom ishodu liječenja.Non-alcoholic fatty liver disease (NAFLD) refers to a condition characterized by the accumulation of triglycerides in hepatocytes in individuals who do not consume significant amounts of alcohol. It represents a range of liver disorders closely associated with metabolic syndrome, and its progressive form, non-alcoholic steatohepatitis (NASH), leads to lipotoxicity, inflammatory hepatocyte injury, and ultimately the development of fibrosis and cirrhosis. In recent years, NASH has become an increasingly common cause of end-stage liver disease and an indication for liver transplantation. Following liver transplantation, NAFLD may reoccur in patients whose primary disease was NASH (recurrence), but it can also develop de novo, especially in the presence of risk factors such as obesity, insulin resistance, type 2 diabetes mellitus, and long-term immunosuppressive therapy. Post-transplant NAFLD is often asymptomatic and discovered incidentally, while diagnostic challenges include the limited reliability of non-invasive methods in transplant recipients. Although liver biopsy remains the gold standard, non-invasive techniques such as elastography are more frequently used in clinical practice. The therapeutic approach is based on non-pharmacological measures, primarily weight reduction and control of metabolic syndrome components. The first drug specifically approved for the treatment of NASH was authorized by the FDA in 2024. Given the increasing prevalence of NAFLD both in the general population and among transplant recipients, early identification, prevention, and regular monitoring are essential for preserving graft function and improving long-term outcomes
Analysis of trends in prevalence and mortality following a ten-year period and prevalence and mortality of esophageal variceal bleeding in patients with liver cirrhosis treated in a tertiary healthcare institution in the Republic of Croatia
No full textAkutno krvarenje iz varikoziteta jednjaka česta je komplikacija u bolesnika s cirozom jetre te predstavlja značajan čimbenik morbiditeta i mortaliteta. Cilj ovog istraživanja je ispitati razlike u prevalenciji, kliničkim značajkama te mortalitetu ovog stanja u bolesnika liječenih u tercijarnoj zdravstvenoj ustanovi u Republici Hrvatskoj u odmaku od deset godina.
Istraživanjem su prikupljeni podaci o sociodemografskim, endoskopskim i kliničkim karakteristikama za 102 bolesnika primljena u Klinički bolnički centar “Sestre milosrdnice” (KBCSM) u Zagrebu zbog akutnog varikoznog krvarenja uslijed dekompenzacije ciroze tijekom dva trogodišnja razdoblja. Prvo između 1. siječnja 2008. godine i 31. prosinca 2010. godine te drugo između 1. siječnja 2020. godine i 31. prosinca 2022. godine. Određena je prevalencija varicealnog krvarenja te klinički ishod i 30-dnevni mortalitet ispitanika, a potom su isti uspoređeni između dvije skupine s obzirom na razdoblje liječenja.
Prevalencija varikoznih krvarenja u bolesnika s cirozom jetre iznosila je 7,2 slučajeva/100 000 stanovnika za razdoblje 2008.-2010., naspram 3,6 slučajeva/100 000 stanovnika u periodu 2020.-2022. (p < 0,001). U oba razdoblja ispitanici su pretežito bili muškarci mlađi od 65 godina, s dugogodišnjom konzumacijom alkohola kao vodećim uzrokom ciroze. 30-dnevni mortalitet iznosio je 14,7% za pacijente od 2008. do 2010. godine te 17,6% za pacijente od 2020. do 2022. godine (p = 0,700).
Prevalencija akutnog krvarenja iz varikoziteta jednjaka se dvostruko smanjila tijekom razdoblja od deset godina, što potvrđuje značajan napredak u profilaktičkom zbrinjavanju bolesnika s cirozom jetre. Međutim, 30-dnevni mortalitet ostao je nepromijenjen, zadržavajući se na relativno visokom postotku i nakon deset godina, što ukazuje na složenost liječenja ove skupine bolesnika.Acute esophageal variceal bleeding is a common complication in patients suffering liver cirrhosis and represents a significant factor in morbidity and mortality. The aim of this study is to examine the differences in prevalence, clinical features, and mortality of this condition in patients treated in a tertiary healthcare institution in the Republic of Croatia following a ten-year period.
The study collected data on sociodemographic, endoscopic, and clinical characteristics of 102 patients admitted to the Clinical Hospital Center “Sestre milosrdnice” (KBCSM) in Zagreb for acute variceal bleeding due to decompensation of cirrhosis, during two three-year periods. The first between January 1, 2008, and December 31, 2010, and the second between January 1, 2020, and December 31, 2022. The prevalence of variceal bleeding, as well as patient clinical outcome and 30-day mortality, were determined, followed by comparison between the two groups with respect to the treatment period.
The prevalence of variceal bleeding in patients with liver cirrhosis was 7,2 cases/100,000 population for the 2008-2010 period, compared to 3,6 cases/100,000 population for the 2020-2022 period (p < 0.001). In both periods, patients were predominantly men under 65 years of age, with long-term alcohol abuse as the leading cause of cirrhosis. The 30-day mortality was 14,7% in patients treated between 2008 and 2010, and 17,6% in those treated between 2020 and 2022 (p = 0.700).
The prevalence of acute esophageal variceal bleeding decreased by half over a ten-year period, confirming significant progress in the prophylactic management of patients suffering liver cirrhosis. However, the 30-day mortality remained unchanged, persisting at a relatively high rate even after ten years, which highlights the complexity of treating these patients
TIM-3 and LAG-3 ligand expression in the nephroblastoma microenvironment
No full textWilmsov tumor, drugog imena nefroblastom, najčešći je tumor bubrega u djece 0.5-16 godina, a sastoji se od tri komponente: blastemske, epitelne i stromalne. Današnji protokoli liječenja, koji kombiniraju kemoterapiju i operativno uklanjanje tumora (a u slučaju metastatske bolesti i bilateralnog nefroblastoma i radioterapiju), doveli su do znatnijeg povećanja preživljenja koje danas doseže i do 90%. Iako je to tako, nuspojave kemoradioterapije ostavljaju trajne posljedice na pacijente što snizuje njihovu kvalitetu života. Također, pacijenti koji dožive recidive imaju stopu preživljenja koja iznosi oko 50%. Zbog tih se razloga istražuju novi modaliteti dijagnostike i liječenja. Tumorski imunomikrookoliš predstavlja stanice imunološkog sustava te njihove produkte koji svojom inhibicijom komponenata imunološkog sustava domaćina mogu smanjiti anti-tumorski odgovor organizma te promovirati rast, invaziju i metastaziranje tumora. U posljednje vrijeme puno je istraživanja fokusirano na razvijanje lijekova koji djeluju na komponente tumorskog imunomikrookoliša te su u praksu za neke tumore odrasle i dječje dobi uvedeni lijekovi s inhibitornim djelovanjem na njih. Cilj ovog istraživanja bio je odrediti postoji li prisutnost liganada tumorskog imunomikrookoliša TIM-3 i LAG-3 u nefroblastomu. Imunohistokemijska analiza provedena je na 23 uzorka nefroblastoma dijagnosticiranih u periodu 2018.-2023. godine, a odabranih pretraživanjem arhive parafinskih blokova Klinike za patologiju i citologiju “Ljudevit Jurak” KBC Sestre milosrdnice. Rezultati su pokazali da oba navedena liganda, TIM-3 i LAG-3, imaju najveći prosječni postotak pozitivnih stanica te prosječni intenzitet reakcije u stromalnoj komponenti nefroblastoma. Iako je ta ekspresija za oba liganda postigla statističku značajnost (p < 0.001), ekspresija TIM-3 znatno je veća od ekspresije LAG-3. U epitelnoj i blastemskoj komponenti pronađena je manja ekspresija TIM-3 nego u stromalnoj bez statistički značajne razlike među njima (p = 0.383), dok ekspresije LAG-3 u njima nije bilo. Ove rezultate potrebno je potvrditi na većoj kohorti te bi bilo korisno istražiti može li se povećana ekspresija nekog od ovih markera povezati sa višim stadijem ili rizikom bolesti ili s povećanom vjerojatnosti recidiva.Wilms tumor, also called nephroblastoma, is the most common type of renal tumor in children aged 0.5-16 years and it is composed out of three components: blastemal, epithelial and stromal. Present-day therapy protocols, which combine the use of chemotherapy and surgical removal of tumor (in case of metastatic disease and bilateral Wilms tumor radiotherapy is added), resulted in increase of survival rates which reach up to 90%. Even though that is the case, side effects of chemoradiotherapy leave lasting issues lowering patients' life quality. Also, patients who experience recurrence have survival rate of about 50%. Because of mentioned arguments, new diagnostic and treatment modalities are being explored. Tumor microenvironment contains immune cells and their products which can diminish organism's anti-tumor response and promote tumor growth, invasion and metastasis by inhibiting components of host's immune system. Lately there was a lot of research focused on developing therapy that targets tumor microenvironment components which led to introduction of medicines with inhibitory acitivity on said components into therapy regimes for both adult and pediatric tumors. The goal of this study was to determine if tumor microenvironment ligands TIM-3 and LAG-3 are present in nephroblastoma. Immunohistochemical staining was performed on 23 nephroblastoma samples diagnosed from year 2018 to 2023, selected from formalin fixed, paraffin embedded tissue archive in Clinical Department of Pathology and Cytology „Ljudevit Jurak“. Results showed that the stromal component of nephroblastoma expressed TIM-3 and LAG-3 more frequently than the epithelial and blastemal components, with a statistically significant difference (p < 0.001). The frequency of TIM-3 expression was lower in the epithelial and blastemal components, without a statistically significant difference between them (p = 0.383). There was no LAG-3 expression in the epithelial and blastemal components. Our results could be relevant to investigate further on a larger sample cohort and to analyse potential correlations with tumor stage and risk classification or larger possibility of recurrence
Pathophysiological role of inhalational anesthetics in cancer biology
No full textInhalacijski anestetici rutinski se koriste za održavanje anestezije u kirurškom liječenju onkoloških pacijenata. Danas su u primjeni hlapljivi, halogenirani anestetici - izofluran, desfluran i najčešće korišteni sevofluran. Osim osnovnog anestetičkog učinka, pokazano je da aktivacijom različitih unutarstaničnih puteva mogu inducirati staničnu prilagodbu na ishemijsko-reperfuzijsku ozljedu, poznatu kao prekondicioniranje anesteticima koje je najviše istraživano na neuronima i kardiomiocitima. Također, inhalacijski anestetici suprimiraju imunološki sustav koji je jedan od ključnih obrambenih mehanizama protiv razvoja i metastaziranja malignih bolesti. U novije vrijeme raste interes za njihovu ulogu u biologiji tumora, s ciljem utvrđivanja mogu li izravno, mehanizmima poput prekondicioniranja ili neizravno, supresijom imunološkog sustava, pogodovati rastu i metastaziranju tumora te lošijim dugoročnim onkološkim ishodima. Pretklinička istraživanja na staničnim linijama i životinjskim modelima pokazuju da inhalacijski anestetici mogu imati i protutumorske i povoljne učinke na tumorske stanice. Rezultati ovise ponajviše o vrsti tumora, ali i o vremenu izlaganja, koncentraciji i vrsti korištenog anestetika. Koncentracija i vrijeme izlaganja ne razlikuju se znatno među istraživanjima te se uglavnom koriste klinički relevantni uvjeti. Ipak, u ekstremno visokim dozama i produljenom djelovanju, anestetici djeluju citotoksično i na tumorske i na zdrave stanice. Kliničke studije uglavnom uspoređuju dugoročne onkološke ishode, poput ukupnog preživljenja i vremena do povrata bolesti, između bolesnika koji su primali inhalacijske anestetike i onih koji su primali propofol, koji u pretkliničkim istraživanjima pokazuje potencijalno povoljniji učinak na imunološki odgovor i protutumorsko djelovanje. Rezultati metaanaliza govore u prilog propofolu kao boljem izboru od inhalacijskih anestetika, no rezultati nisu jednoznačni za sva tumorska sijela. Također, za mnoga sijela nije proveden dovoljan broj istraživanja da bi se mogli donijeti validni zaključci. Drugi nedostatak kliničkih studija je njihov uglavnom retrospektivni dizajn, što pridonosi riziku od pristranosti. Potrebna su daljnja prospektivna, randomizirana kontrolirana klinička istraživanja kako bi se razjasnio učinak inhalacijskih anestetika na biologiju raka i njihov utjecaj na dugoročne ishode onkoloških bolesnika, te kako bi se anesteziološki plan mogao optimalno prilagoditi u onkološkoj kirurgiji.Volatile anesthetics are routinely used to maintain anesthesia during the surgical treatment of oncology patients. Currently, volatile halogenated anesthetics, such as isoflurane, desflurane, and the most commonly used, sevoflurane, are in clinical use. In addition to their primary anesthetic effects, these agents have been shown to activate various intracellular pathways that can induce cellular adaptation to ischemia-reperfusion injury, a phenomenon known as anesthetic preconditioning. This effect has been most extensively studied in neurons and cardiomyocytes. Volatile anesthetics also suppress the immune system, which represents a key defense mechanism against tumor development and metastasis. In recent years, interest has grown in their role in tumor biology, aiming to determine whether they might directly, through mechanisms such as preconditioning, or indirectly, via immunosuppression, promote tumor growth and metastasis, and reduce long-term survival. Preclinical studies using cell lines and animal models have shown that volatile anesthetics can exert both antitumor and tumor-promoting effects, depending primarily on a tumor type, as well as on exposure time, concentration, and the specific anesthetic used. Concentration and exposure time generally do not vary significantly between studies and are mostly within clinically relevant ranges. However, at extremely high doses and with prolonged exposure, anesthetics exert cytotoxic effects on both tumor and healthy cells. Clinical studies have primarily compared long-term oncologic outcomes, such as overall survival and time to recurrence, between patients receiving volatile anesthetics and those receiving propofol, which in preclinical studies appears to have a more favorable impact on immune response and tumor biology. Meta-analyses tend to support propofol as a better choice than volatile anesthetics, but findings are not consistent across all tumor types. Additionally, for many cancer types, an insufficient number of studies have been conducted to draw definitive conclusions. Another major limitation of clinical studies is their mostly retrospective design, which increases the risk of bias. Further prospective, randomized controlled clinical trials are needed to clarify the effects of volatile anesthetics on cancer biology and their influence on long-term oncologic outcomes, in order to enable optimal anesthetic planning in oncologic surgery
Secretory otitis in children
No full textSekretorni otitis najčešći je uzrok gubitka sluha u pedijatrijskoj populaciji te je jedna od najčešćih pedijatrijskih bolesti uopće. Prema epidemiološkim podacima, do 90 % djece doživi barem jednu epizodu ove bolesti prije polaska u školu, najčešće između šestog mjeseca i četvrte godine života. Razvoju sekretornog otitisa pogoduju brojni rizični faktori, primjerice: ponavljajuće infekcije gornjih dišnih puteva, kraniofacijalne malformacije, hipertrofija adenoidnih vegetacija i druga stanja koja dovode do opstrukcije Eustahijeve cijevi, te alergije. Od okolišnih faktora najvažniji su boravak u kolektivima poput vrtića, jesensko i zimsko razdoblje godine, izloženost duhanskom dimu te loši socioekonomski uvjeti. Točan uzrok nastanka sekretornog otitisa ostaje nepotpuno razjašnjen. Istraživanja ukazuju na multifaktorsku etiologiju, ali najvažniji i središnji čimbenik je disfunkcija Eustahijeve cijevi. Sekretorni otitis može biti akutnog ili kroničnog tijeka. Bolest se definira kao neinfektivna i nesupurativna upala srednjeg uha u kojoj dolazi do nakupljanja tekućine u kavumu i mastoidu. Klinička je slika u velikom broju slučajeva potpuno asimptomatska, što otežava pravovremeno prepoznavanje. Konduktivni gubitak sluha glavni je simptom ovog stanja koje može imati značajan utjecaj na kvalitetu života i na funkcionalno zdravstveno stanje djece i onih koji se o njima brinu. Postavljanje dijagnoze temelji se na anamnezi, kliničkom pregledu te primjeni objektivnih dijagnostičkih metoda, među kojima su najvažnije otoskopski ili otomikroskopski pregled uha, timpanometrija, tonska i bihevioralna audiometrija te druge metode određivanja praga sluha. Djeci bez prethodnih oštećenja slušnih koščica, poremećaja sluha ili drugih bolesti srednjeg uha preporučuje se konzervativni pristup praćenjem bez liječenja tijekom razdoblja do tri mjeseca. U tom periodu bolest se u većini slučajeva spontano povuče. Ako su simptomi dugotrajni i intenzivni ili su prisutne dodatne patologije indicirano je kirurško liječenje koje uključuje ugradnju ventilacijskih cjevčica i adenoidektomiju.Secretory otitis is the most common cause of hearing loss in the pediatric population and is one of the most common pediatric diseases in general. According to epidemiological data, up to 90% of children experience at least one episode of this disease before starting school, most often between the ages of six months and four years. Numerous risk factors contribute to the development of secretory otitis, such as recurrent upper respiratory tract infections, craniofacial malformations, adenoid hypertrophy and other conditions leading to Eustachian tube obstruction, and allergies. The most important environmental factors include attending daycare or preschool, the autumn and winter seasons, exposure to tobacco smoke, and poor socioeconomic conditions. The exact cause of secretory otitis remains incompletely understood. Research indicates a multifactorial etiology, but the most important and central factor is Eustachian tube dysfunction. Secretory otitis can be acute or chronic. The disease is defined as a non-infectious and non-suppurative inflammation of the middle ear characterized by the accumulation of fluid in the tympanic cavity and mastoid. Clinical presentation is often completely asymptomatic, which makes timely recognition difficult. Conductive hearing loss is the main symptom of this condition, and it can significantly impact the quality of life and functional health of children and their caregivers. Diagnosis is based on the patient's medical history, clinical examination, and objective diagnostic methods. The most important of these include otoscopic or otomicroscopic ear examination, tympanometry, pure-tone and behavioral audiometry, and other methods for determining hearing thresholds. For children without pre-existing damage to the ossicles, hearing disorders, or other middle ear diseases, a conservative approach is recommended. This involves „watchful waiting“ for up to three months, as the condition often resolves spontaneously during this period. If symptoms are long-lasting and intense or additional pathologies are present, surgical treatment is indicated, which includes the installation of ventilation tubes and adenoidectomy
Relation between psychic disorders and the immune system
No full textPsihoneuroimunološka istraživanja upućuju na značajnu dvosmjernu povezanost imunološkog i središnjeg živčanog sustava u razvoju i održavanju psihičkih poremećaja. Poremećaji poput depresije, anksioznosti, posttraumatskog stresnog poremećaja, shizofrenije i poremećaja iz spektra autizma povezani su s perzistentnom sistemskom upalom i disregulacijom osovine hipotalamus-hipofiza-nadbubrežna žlijezda (HHN). U serumu i cerebrospinalnom likvoru ovih pacijenata često se pronalaze povišene koncentracije pro-upalnih citokina poput interleukina (IL)-6, faktora tumorske nekroze alfa (TNF-α) i interleukina-1β (IL- 1β). Kronični stres, aktivacijom HHN osi i simpatičkog živčanog sustava, potiče osolobađanje kateholamina i glukokortikoida, što dugoročno može dovesti do glukokortikoidne rezistencije i održavanja upalnog stanja. Istovremeno, promjene u sastavu crijevne mikrobiote i propusnosti crijevne barijere dodatno narušavaju neuroimunološku ravnotežu. Također, narušeni mehanizmi neurogeneze, sinaptičke plastičnosti i ekscitotoksičnosti povezani su s povećanom proizvodnjom neurotoksičkih metabolita u kinureninskom putu metabolizma triptofana. Dokazano je da protuupalni učinci određenih psihofarmaka, uključujući selektivne inhibitore ponovne pohrane serotonina (SIPPS) i selektivne inhibitore ponovne pohrane noradrenalina (SIPPN), djelomično posreduju njihovu učinkovitost, dok terapija probioticima, postbioticima i fekalna transplantacija predstavljaju nove potencijalne metode za koje su potrebna daljnja istraživanja. Identifikacija imunoloških biomarkera mogla bi koristiti u sekundarnoj prevenciji kao i personaliziranom terapijskom pristupu.Psychoneuroimmunological research highlights a significant bidirectional connection between the immune system and the central nervous system in the development and maintenance of psychiatric disorders. Conditions such as depression, anxiety, post-traumatic stress disorder, schizophrenia, and autism spectrum disorders have been associated with persistent systemic inflammation and dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis. Elevated levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β) are frequently detected in the serum and cerebrospinal fluid of affected individuals. Chronic stress, by activating the HPA axis and sympathetic nervous system, promotes the release of catecholamines and glucocorticoids, which over time may lead to glucocorticoid resistance and the perpetuation of inflammatory states. Concurrently, alterations in gut microbiota composition and increased intestinal permeability further disrupt neuroimmune homeostasis. Additionally, impaired mechanisms of neurogenesis, synaptic plasticity, and excitotoxicity have been linked to the increased production of neurotoxic metabolites through the kynurenine pathway of tryptophan metabolism. Anti-inflammatory effects of certain psychotropic medications, including selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs), have been shown to partially mediate their therapeutic efficacy. Meanwhile, emerging treatments such as probiotics, postbiotics and fecal microbiota transplantation represent promising strategies that require further investigation. The identification of immunological biomarkers could prove valuable in secondary prevention and support a more personalized therapeutic approach
Patent foramen ovale in adults
No full textOtvoreni foramen ovale (PFO) predstavlja komunikacijski kanal koji povezuje desni i lijevi atrij, a nastaje kao posljedica nepotpunog zatvaranja normalne fetalne strukture nakon rođenja te se njegova učestalost u odrasle populacije procjenjuje na 15-35%. Najčešće ne uzrokuje simptome, ali njegova prisutnost može imati klinički značaj, osobito kod mladih osoba s kriptogenim moždanim udarom. Mehanizam paradoksalne embolije, kod koje tromb preko PFO-a prolazi iz venske u arterijsku cirkulaciju, glavni je razlog njegove povezanosti s ishemijskim incidentima. PFO se otkriva pomoću ehokardiografije s kontrastom, transezofagealne ehokardiografije i transkranijskog Dopplera. Terapijske mogućnosti uključuju farmakološku prevenciju tromboembolije ili zatvaranje PFO-a. Zatvaranje PFO-a provodi se perkutanim putem pri čemu se koristi posebno oblikovan uređaj za trajnu okluziju otvora. Postupak zatvaranja može imati preventivni učinak kod pacijenata s prethodnim kriptogenim moždanim udarom, a najčešća komplikacija nakon zatvaranja je atrijska fibrilacija. Osim moždanog udara, PFO se povezuje i s migrenom, sindromom platipneje-ortodeoksije, dekompresijskom bolešću kod ronilaca te plućnim edemom na velikim visinama. Iako patofiziološki mehanizmi nisu u potpunosti razjašnjeni, zajednička je mogućnost desno-lijevog šanta koji omogućuje prolaz embolijskih materijala, plinova ili vazoaktivnih tvari u sistemsku cirkulaciju. U kontekstu tih kliničkih stanja, važna je individualizirana dijagnostička obrada i selekcija pacijenata za perkutano zatvaranje PFO-a u cilju smanjenja rizika od komplikacija i poboljšanja ishoda liječenja.Patent foramen ovale (PFO) is a communication channel between the right and left atrium, resulting from incomplete closure of a normal fetal structure after birth. It's prevalence in the adult population is estimated at 15-35%. although most individuals remain asymptomatic, PFO may have clinical significance, particulary in younger patients with cryptogenic ischemic stroke. The primary mechanism linking PFO to ischemic events is paradoxical embolism, in which a thrombus passes from the venous to the arterial circulation through the PFO. Diagnosis relies on contrast-enhances transthoracic echocardiography, transesophageal echocardiography and transcranial Doppler ultrasound. Therapeutic options include pharmacological prevention of thromboembolism or percutaneous PFO closure using a specially designed occlusion device. The closure procedure may providepreventive benefit in patients with prior cryptogenic stroke, with atrial fibrillation being the most common post-procedural complication. Beyond stroke, PFO nas been associated with several other clinical conditions, including migraine, platypnea-orthodeoxia syndrome, decompression sickness in divers and high-altitude pulmonary edema. Although the underlying pathophysiological mechanism are not fully elucidated, a common factor is the presence of a right-to-left shunt, which allows the passage of embolic material, gas bubbles or vasoactive substances into the systemic circulation. In such clinical contexts, individualized diagnostic assessement and patient selection for percutaneous PFO closure are essential to reduce the risk of complications and improve treatment outcomes
Unidentified bodies examined at Institute of Forensic Medicine and Criminalistics between 2023 and 2024
No full textUtvrđivanje identiteta pronađenog tijela temelji se na multidisciplinarnoj suradnji i predstavlja izazov u području sudske medicine. U ovom radu analizirani su slučajevi tijela nepoznatog identiteta obrađenih na Zavodu za sudsku medicinu i kriminalistiku tijekom dvogodišnjeg razdoblja. Ukupno je na Zavodu obrađeno 195 takvih tijela, od kojih za njih 15 do pisanja ovog rada identitet nije bio utvrđen. Naglasak je stavljen na opisnu analizu podataka i povezanost između stanja tijela, metode identifikacije i trajanja procesa identifikacije. Podatci su prikupljeni iz sudskomedicinskih zapisnika i forenzičkih nalaza, a statističkom analizom ispitivana je povezanost između različitih varijabli. Rezultati su pokazali da su brže identificirana ona tijela koja su bila boljeg stanja te koja su identificirana metodom daktiloskopije i vizualnog prepoznavanja. Sporije su identificirana tijela lošijeg stanja i ona koja su identificirana analizom DNK. Također, utvrđena je pozitivna korelacija između vremena proteklog od smrti do pronalaska tijela i trajanja identifikacije. Medijan vremena do pronalaska tijela iznosio je 6 dana, a do identifikacije 4 dana uz postojanje nekoliko dosta odstupajućih vrijednosti. Do identifikacije se u 91,6 % slučajeva došlo upotrebom primarnih metoda, najvećim dijelom daktiloskopskim vještačenjem, a manjim dijelom analizom DNK. Dobivena saznanja naglašavaju važnost kvalitetne pribave i razmjene podataka, pravovremene prijave nestanaka i kvalitetne međuinstitucionalne suradnje s pristupom bazama podataka.The determination of identity of a found body is based on multidisciplinary cooperation and represents a challenge in the field of forensic medicine. This paper analyses cases of bodies of unknown identity examined at the Institute of Forensic Medicine and Criminalistics over a two-year period. A total of 195 unidentified bodies were processed at the Institute, 15 of which had not been identified by the time of writing. Emphasis was placed on descriptive data analysis and the relationship between the condition of the body, the identification method and the duration of the identification process. Data were collected from forensic medical records and forensic findings, and statistical analysis examined the relationship between different variables. The results showed that bodies in better condition and those identified by dactyloscopy and visual recognition were identified more quickly. Bodies in worse condition and those identified by DNA analysis were identified more slowly. A positive correlation was also found between the time from death to finding the body and the duration of the identification process. The median time until the body was found was 6 days, and until identification was 4 days, with the existence of several significantly deviating values. In 91,6 % of cases, identification was achieved using primary methods, mostly dactyloscopic expertise, and to a lesser extent through DNA analysis.
The findings emphasize the importance of quality acquisition and exchange of data, timely reporting of disappearances and quality inter-institutional cooperation with access to databases