Veterinary medicine - Repository of PHD, master's thesis
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Nakladnička djelatnost Škole narodnog zdravlja „Andrija Štampar“ od 1947. do 2023. godine
No full textVažnost objave inovativnih kirurških tehnika u znanstvenim časopisima – primjer iz Kliničkog bolničkog centra Zagreb
No full textThe use of deep brain stimulation in the treatment of refractory epilepsy
No full textDuboka mozgovna stimulacija važna je neurokirurška metoda za mnoge bolesti. Najučinkovitija se pokazala u liječenju poremećaja kretanja, ali ima i ulogu u liječenju refrakterne epilepsije. Epilepsija je jedna od najčešćih neuroloških bolesti koja se manifestira nenormalnom sinkroniziranom neuronskom aktivnošću u mozgu. Etiološki se epilepsije dijele na strukturalne, genske, infektivne, metaboličke, imunosne i nepoznate. Antiepileptičkim lijekovima uspješno se može liječiti većina, ali trećina pacijenata s epilepsijom nema odgovarajući odgovor na medikamentozno liječenje, što ih čini potencijalnim kandidatima za neurokirurško liječenje. Duboka mozgovna stimulacija za refrakternu epilepsiju za sada je sekundarna metoda jer ne postiže potpunu slobodu od epileptičkih napadaja kao što se to očekuje od kirurške struke. Najčešće se kao meta stimulacije koristi rostralna jezgra talamusa koja ima najviše dokaza o sigurnosti i učinkovitosti u smanjenju frekvencije epileptičkih napadaja. Istražuju se i druge jezgre talamusa od kojih je najzanimljivija centromedijana jezgra te područja poput hipokampusa, piriformnog korteksa, medijalnog septuma i subtalamičke jezgre. Važno je napomenuti da epilepsija može značajno narušiti kvalitetu života pacijenata te da su potrebna daljnja istraživanja za optimizaciju terapije i smanjenje nuspojava. Sa stalnim razvojem dijagnostike i novih tehnologija, očekuje se napredak u uspješnosti ovih postupaka.Deep brain stimulation is an important neurosurgical method for treating various diseases. It has proven to be most effective in treating movement disorders, but it also plays a role in managing refractory epilepsy. Epilepsy is one of the most common neurological disorders, characterized by abnormal synchronized neuronal activity in the brain. Epilepsy can be classified etiologically into structural, genetic, infectious, metabolic, immune-related, and unknown causes. While the majority of epilepsy cases can be successfully treated with antiepileptic drugs, about one-third of patients do not respond adequately to medication, making them potential candidates for neurosurgical treatment. Deep brain stimulation for refractory epilepsy is currently a secondary method, as it does not achieve complete seizure freedom as expected in surgical practice. The most commonly targeted area for stimulation is the anterior thalamic nucleus, which has the most evidence supporting its safety and effectiveness in reducing seizure frequency. Other thalamic nuclei, such as the centromedian nucleus, as well as regions like the hippocampus, piriform cortex, medial septum and subthalamic nucleus, are also being investigated. It is important to note that epilepsy can significantly impair the quality of life for patients and further research is needed to optimize therapy and reduce side effects. With the continuous advancement of diagnostics and new technologies, improvements in the success of these procedures are expected
The influence of prior statin therapy on the course and outcome of pneumonia
No full textLijekovi iz skupine statina putem inhibicije enzima HMG-CoA-reduktaze smanjuju razinu kolesterola u krvi. Kroz godine njihove široke primjene otkriveni su dodatni pleiotropni učinci statina. Pokazalo se da statini posjeduju i antiupalna, antioksidativna, antiagregacijska i antiproliferacijska svojstva. Glavni cilj ovog istraživanja bio je utvrditi utjecaj navedenih svojstava na ishod i tijek pneumonije.
U provedenoj studiji retrospektivno je promatrano 149 pacijenata koji su u razdoblju od 1. siječnja 2023. do 1. siječnja 2024. obrađeni na OHBP-u Kliničkog bolničkog centra Zagreb radi pneumonije. Za pacijente sa statinima i pacijente bez statina u terapiji, definirani su pokazatelji težine bolesti (hipoksemija, tahikardija, febrilitet, hipotenzija, ARI, dezorjentiranost pri pregledu, hiperglikemija, hiponatremija, PSI, CURB-65, potreba za hospitalizacijom, trajanje hospitalizacije, povratak u hitnu zbog povezanog razloga te ishode).
Pronađena je korelacija između terapije statinima i navedenih pokazatelja težine bolesti. PSI ljestvica, prisutnost tahikardije, hipotenzije, ARI, potreba za oksigenoterapijom i postotak hospitaliziranih pacijenata ukazivali su na blaži tijek bolesti u pacijenata na terapiji statinima, dok je prisutstvo dezorijentiranosti i ishod bolesti bio podjednak u obje skupine pacijenata.
Rezultati su u skladu s rezultatima drugih studija koje su proučavale učinak statina na druge upalne bolesti.
Buduće prospektivne studije s većim brojem pacijenata i jasno definiranim ishodima bolesti upotpuniti će rezultate ovog istraživanja i jasnije definirati potencijalnu praktičnu primjenu dokazanog.Medications from the statin group lower blood cholesterol levels by inhibiting the enzyme HMG-CoA reductase. Over years of widespread use, additional pleiotropic effects of statins have been discovered. Statins have been shown to possess anti-inflammatory, antioxidant, anti-aggregatory, and antiproliferative properties. The main aim of this research was to determine the impact of these properties on the course and outcome of pneumonia.
In this retrospective study, 149 patients who were treated at the Emergency Department of the Clinical Hospital Center Zagreb for pneumonia between January 1, 2023, and January 1, 2024, were observed. Indicators of disease severity (hypoxemia, tachycardia, fever, hypotension, ARI, disorientation during examination, hyperglycemia, hyponatremia, PSI, CURB-65, need for hospitalization, length of hospital stay, return to the emergency department for a related reason, and outcomes) were defined for patients on statin therapy and those without statins in their treatment.
A correlation was found between statin therapy and the aforementioned indicators of disease severity. The PSI scale, presence of tachycardia, hypotension, ARI, need for oxygen therapy, and the percentage of hospitalized patients indicated a milder course of disease in patients on statin therapy, while the presence of disorientation and the outcome of the disease were similar in both patient groups.
The results are consistent with those of other studies that have examined the effects of statins on other inflammatory diseases.
Future prospective studies with a larger number of patients and clearly defined disease outcomes will complement the results of this research and more clearly define the potential practical application of the findings
Endovascular treatment of intracranial arteriovenous fistulas
No full textIntrakranijske duralne arteriovenske fistule (DAVF) patološki su spojevi između duralnih arterija i duralnih venskih sinusa, kortikalnih vena ili meningealnih vena. DAVF čine 10 do 15% svih intrakranijskih vaskularnih malformacija. Najčešće se radi o stečenim lezijama nepoznate etiologije čija je pojava povezana s trombozom intrakranijskih venskih sinusa koja vodi u razvoj venske hipertenzije. DAVF se kategoriziraju pomoću Cognardove i Bordenove klasifikacije, koje u obzir uzimaju lokalizaciju lezija i lokalizaciju venske drenaže, angiostrukturu, prisutnost/odsutnost kortikalne venske drenaže i smjer protoka krvi. Korištenjem postojećih klasifikacija, određuje se tip lezije na temelju čega se odabire vrsta terapijskog liječenja. Klinička prezentacija varira ovisno o lokaciji lezija i tipu venske drenaže, što obuhvaća raspon od asimptomatskih lezija sve do potencijalno smrtonosnih lezija uslijed rupture i cerebralnog krvarenja. Digitalna suptrakcijska angiografija predstavlja zlatni standard dijagnostike DAVF. Terapijske mogućnosti uključuju konzervativno liječenje, radiokirurško liječenje, endovaskularne intervencije i operativno liječenje, pri čemu se odluka temelji na čimbenicima poput tipa lezije, lokacije lezije i pacijentove osobne anamneze i trenutnog stanja. Prva linija liječenja fistula je endovaskularna intervencija, transarterijskim ili transvenskim putem, s ciljem kompletnog zatvaranja fistule kako bi se uklonili simptomi i prevenirale potencijalne komplikacije.Intracranial dural arteriovenous fistulas (DAVF) are pathological connections between dural arteries and dural venous sinuses, cortical veins, or meningeal veins. DAVFs constitute 10 to 15% of all intracranial vascular malformations. They are most commonly acquired lesions of unknown etiology, whose occurrence is associated with intracranial venous sinus thrombosis leading to the development of venous hypertension. They are classified using the Cognard and Borden classifications, which take into account the localization of lesions and venous drainage, angioarchitecture, presence/absence of cortical venous drainage, and direction of blood flow. The type of the lesion is determined using available classifications, which helps decide which therapeutic option to use. The clinical presentation varies depending on the location of the lesions and the type of venous drainage, ranging from asymptomatic lesions to potentially fatal lesions due to rupture and cerebral hemorrhage. Digital subtraction angiography is the gold standard for diagnosing DAVFs. Therapeutic options include conservative treatment, radiation therapy, endovascular interventions, and surgical treatment, with the decision based on factors such as the type and location of the lesion, and the patient's personal history and current condition. The first-line treatment for fistulas is endovascular intervention, either transarterial or transvenous, aiming for complete fistula closure to cure the symptoms and prevent potential complications
Physical activity during pregnancy
No full textTrudnoća je posebno razdoblje u životu svake žene ispunjeno radošću, iščekivanjem i promjenom kako u fiziološkom tako i u psihološkom smislu. Često, zbog osjećaja zabrinutosti i straha, žene prestaju ili uvelike smanjuju fizičku aktivnost za vrijeme trudnoće. Ovaj diplomski rad napisan je kako bi ohrabrio trudnice na nastavak ili započinjanje fizičke aktivnosti u trudnoći te potaknuo interes medicinskih djelatnika za ovu temu. Uz pregled trenutnih preporuka nadležnih ginekoloških i opstetričkih društava te kratkog osvrta na prošlost, u radu se ističu anatomske, kardiovaskularne, respiratorne te mnoge druge promjene i povezuju se s važnošću i utjecajem fizičke aktivnosti u trudnoći. Nadalje, pomnije su obrađene posebne vrste treninga te aktivnosti koje bi trudna sportašica trebala izbjegavati pri čemu se naglašavaju patofiziološki mehanizmi i procesi u podlozi. Naposljetku, kao najvažniji dio ovog rada identificiraju se dobrobiti i rizici aktivnog načina života u ,,drugom stanju’’.
S obzirom na rastuću prevalenciju žena sportašica, rasprava o fizičkoj aktivnosti u trudnoći sve je češća i zahtijeva multidisciplinarni pristup liječnika, fizioterapeuta i kineziologa koji jedino zajedničkim snagama, istraživanjima i znanjem mogu pružiti individualizirani pristup svakoj ženi te joj, ako uvjeti to dozvoljvaju, omogućiti aktivnu i sigurnu trudnoću.Pregnancy is a special period in every woman's life, filled with joy, anticipation, and change, both physiologically and psychologically. Often, due to feelings of concern and fear, women stop or significantly reduce physical activity during pregnancy. This thesis is written to encourage pregnant women to continue or start physical activity during pregnancy and to stimulate the interest of medical professionals in this topic. Along with a review of current recommendations from relevant gynecological and obstetric societies and a brief overview of the past, the paper highlights anatomical, cardiovascular, respiratory, and many other changes and links them to the importance and impact of physical activity during pregnancy. Furthermore, specific types of training and activities that a pregnant athlete should avoid are examined more closely, with an emphasis on the underlying pathophysiological mechanisms and processes. Finally, the most important part of this paper identifies the benefits and risks of an active lifestyle during pregnancy.
Given the growing prevalence of female athletes, the discussion about physical activity during pregnancy is becoming more frequent and requires a multidisciplinary approach involving doctors, physiotherapists, and kinesiologists who, through joint efforts, research, and knowledge, can provide an individualized approach to each woman and, if conditions allow, enable an active and safe pregnancy
Magnetic resonance imaging in postoperative follow up of patients with breast cancer
No full textCilj ovog rada bio je utvrditi dijagnostičke performanse magnetske rezonancije (MR) dojki u tijeku petogodišnjeg postoperativnog praćenja bolesnica s karcinomom dojke u detekciji malignih lezija u dojkama. U retrospektivno istraživanje je uključeno 77 bolesnica kojima je učinjen preoperativni MR dojki, kirurški zahvat i koje imaju dostupan barem jedan MR pregled dojki učinjen u sklopu petogodišnjeg postoperativnog praćenja interpretiran prema BI-RADS klasifikaciji. Mjere dijagnostičke točnosti postoperativne MR dojke za detekciju maligne lezije u dojci izračunate su korištenjem različitih kombinacija BI-RADS kategorija. Retrospektivnom analizom 236 MR pregleda dojki detektirano je ukupno 6 malignih lezija u dojkama. Bolesnice s lobularnim karcinomom dojke imaju 6,3 puta veću šansu razviti malignu leziju u dojci u petogodišnjem postoperativnom razdoblju od bolesnica s karcinomom dojke nespecificiranog tipa. Ispitivanjem dijagnostičkih performansi različitih kombinacija BI-RADS kategorija za detekciju maligne lezije u dojci, utvrđeno je da se u slučaju kombinacije BI-RADS kategorija 3, 4, 5 postiže osjetljivost od 100% i specifičnost od 86%. Za razliku od toga, kombinacija samo BI-RADS kategorija 4 i 5 poboljšala je specifičnost na 94%, ali je rezultirala manjom osjetljivosti (63%) čime je previđen jedan karcinom dojke. Također, prilikom MR pregleda dojki u dvije bolesnice su detektirane i ekstramamarne promjene koje su pokazale udaljenu diseminaciju karcinoma dojke. Kao zaključak, za bolju detekciju malignih lezija u dojkama važno je uključiti kombinaciju BI-RADS kategorija 3, 4 i 5. To rezultira nešto nižom specifičnosti i dovodi do daljnje dijagnostičke obrade kod dijela bolesnica, no jedino tako postižemo osjetljivost od 100% što je nužno u toj skupini bolesnika jer su upravo one pod većim rizikom razvoja maligne lezije u dojci.The aim of this study was to determine diagnostic performance of magnetic resonance imaging (MRI) in detection of malignant lesions in the breast during five year postoperative follow-up of patients with breast cancer. This retrospective study included 77 patients who had at least one preoperative MRI between January 1st, 2015 and December 31st, 2016. Diagnostic accuracy of MRI in detection of malignant lesions was calculated for different combinations of BI-RADS categories. During retrospective evaluation of 236 MRI images, 6 malignant lesions were detected in breasts. Patients with invasive lobular carcinoma have a 6,3 times greater chance of disease recurrence in five year postoperative follow-up compared to patients with no special type breast cancer. While determining performance of breast MRI for different combinations of BI-RADS categories in detection of malignant lesions in the breast, results showed that in case of BI-RADS categories 3, 4 and 5 sensitivity is 100% and specificity is 86%. In contrast, in the case of combination of BI-RADS categories only 4, 5 specificity (94%) was improved, but sensitivity was 63%, which resulted in missing one malignant lesion. Additionally, in two patients extramammary lesions, later confirmed as distant metastases, were found. In conclusion, for better detection of malignant lesions, it is important to include BIRADS categories 3, 4, 5. That results with lower specificity and leads to further diagnostic in a certain number of patients, but it is the only method of achieving sensitivity of 100%, which is necessary in this patient group since they are under higher risk of malignant lesions in the breast
Association between atopic phenotype and clinical-endoscopic features of pediatric eosinophilic esophagitis
No full textEozinofilni ezofagitis (EoE) kronična je bolest posredovana imuno/antigenim patofiziološkim mehanizmima, karakterizirana predominantno eozinofilnom upalom sluznice jednjaka. Ekspozicija određenim nutritivnim i/ili inhalacijskim alergenima, kao najčešći okidač EoE, potiče citokinsku aktivaciju eozinofila. Privlačenjem drugih upalnih stanica u sluznicu jednjaka, narušava se barijera što je vidljivo u endoskopskim i histološkim nalazima. Klinički se manifestira spektrom simptoma, u djece najčešće kao bol u trbuhu, zatim disfagija, impakcija bolusa hrane i odinofagija. Svjedočimo porastu incidencije i prevalencije EoE zadnjih desetak godina, stoga je evidencija 15-godišnjeg iskustva jednog centra značajna za nastavak praćenja ove poligenske bolesti čije pravodobno liječenje prevenira kronično remodeliranje sluznice i nastanak ezofagealne fibroze. Cilj ovog rada bio je ispitati pojavnost, klinički fenotip i endoskopska obilježja u skupini djece s EoE liječene na Klinici za pedijatriju KBC Sestre milosrdnice, u periodu od 1. siječnja 2009. do 1. siječnja 2024. godine. Podaci su prikupljeni iz digitalne arhive službene bolničke dokumentacije.
U istraživanje je uključeno 36 ispitanika životne dobi 5-17 godina (prosječno 12,78 godina). EoE se klinički najčešće manifestirao bolovima u trbuhu, ukupno 19 (53%) ispitanika. Disfagija (30%), odinofagija (8%) i impakcija bolusa hrane (25%) zabilježeni su isključivo kod dječaka. Od pridruženih atopijskih obilježja, najčešće se javljao alergijski rinitis (30%), zatim astma (25%) i atopijski dermatitis (17%). Kod 72% ispitanika utvrđena je nutritivna, kod 44% inhalacijska senzitizacija. Prilikom postavljanja dijagnoze, važan je histološki nalaz koji opisuje broj eozinofila u uzorku bioptata sluznice jednjaka (upalna infiltracija) te je najveći broj ispitanika (33%) bilježio mikroskopski evaluirano 20-30 eozinofila u VVP (velikom vidnom polju). Prema endoskopskom bodovniku za EoE, EREFS (engl. ‘Endoscopic Reference Score’), najčešće validirane bile su EREFS 2 promjene sluznice jednjaka (33%), zatim podjednako zastupljene EREFS 1 i 3 (22%), a EREFS 4 u manje od 3% bolesnika. Ključan dio istraživanja bio je podijeliti ispitanike u dvije skupine, prema prisutnosti atopije, i usporediti težinu bolesti ovisno o pripadnosti ispitanika pojedinoj skupini. Opisan je teži stupanj promjena prema EREFS bodovniku u ispitanika s prisutnom atopijom te je veća zastupljenost disfagičnih tegoba u toj skupini ispitanika. Ovi rezultati naglašavaju činjenicu da je kod bolesnika s atopijom koji javljaju simptome disfunkcije jednjaka važno sumnjati na EoE i očekivati lokalno uznapredovalu upalu.Eosinophilic esophagitis (EoE) is a chronic disease mediated by immune/antigenic pathophysiological mechanisms, characterized predominantly by eosinophilic inflammation of the esophageal mucosa. Exposure to certain nutritional and/or inhaled allergens stimulates cytokine activation of eosinophils. By attracting other inflammatory cells to the esophageal mucosa, the barrier is disrupted, which is evident in endoscopic and histological findings. Clinically, in children it manifests most commonly as abdominal pain, followed by dysphagia, food bolus impaction, and odynophagia. We have witnessed an increase in prevalence of EoE over the past decade, which makes the documentation of 15 years of experience at a single center significant for the ongoing monitoring of this polygenic disease, whose timely treatment prevents chronic mucosal remodeling and the development of esophageal fibrosis. The aim of this study was to examine the occurrence, clinical phenotype, and endoscopic features in a group of children with EoE treated in the Pediatrics Clinic at Sisters of Charity University Hospital from January 1, 2009, to January 1, 2024. Data were collected from the digital archive of official hospital documentation.
The study included 36 participants aged 5 to17 years (average age 12.78 years). EoE clinically manifested as abdominal pain in 19 (53%) patients. Dysphagia (30%), odynophagia (8%), and food bolus impaction (25%) were recorded exclusively in boys. Among associated atopic features, allergic rhinitis was most common (30%), followed by asthma (25%) and atopic dermatitis (17%). Nutritional sensitization was identified in 72% of patients, inhalational in 44%. For diagnosis, the histological finding describing the number of eosinophils in a biopsy sample of the esophageal mucosa (inflammatory infiltration) is crucial, with the highest number of patients (33%) having 20-30 eosinophils per high power field (HPF). According to the EoE endoscopic scoring system, EREFS (Endoscopic Reference Score), the most commonly validated changes in were EREFS 2 (33%), followed by EREFS 1 and 3 (22%), and EREFS 4 in less than 3% of patients. A key part of the study was dividing patients into two groups based on the presence of atopy and comparing the severity of the disease depending on group membership. A more severe degree of changes, according to the EREFS score, was described in patients with atopy, also with a higher prevalence of dysphagic symptoms. These results emphasize the fact that in patients with atopy who report symptoms of esophageal dysfunction, it is important to suspect EoE and expect locally advanced inflammation
Encephalitis in children and adolescents
No full textEncefalitis je upalna bolest moždanog parenhima koja može uzrokovati poremećaje moždanih funkcija. Prema etiologiji, encefalitisi se dijele na infektivne i neinfektivne, pri čemu su virusi najčešći uzročnici infektivnog encefalitisa u djece. Cilj ovog rada je provesti deskriptivnu epidemiološku analizu bolesnika s encefalitisom dječje dobi liječenih u Klinici za infektivne bolesti "Dr. Fran Mihaljević" od 2006. do 2023. godine te usporediti vjerojatnost dokazivanja etiologije u tri različita razdoblja, s obzirom na uvođenje panela za dokazivanje autoimunih encefalitisa i multiplex PCR meningitis/encefalitis panela koji simultano dokazuje prisutnost većeg broja virusnih uzročnika. U istraživanje su uključeni podaci 243 djece i adolescenata hospitaliziranih u Zavodu za infektivne bolesti djece, prosječne dobi od 8 godina. Rezultati su pokazali uspješno dokazivanje etiologije bolesti u 59,7% bolesnika. Najčešći uzročnici infektivnih encefalitisa bili su KME i VZV, dok je najčešći neinfektivni encefalitis bio ADEM. Analiza podataka nije pokazala značajno povećanje vjerojatnosti dokazivanja etiologije uvođenjem novih dijagnostičkih metoda. S toga treba zaključiti da je akutni encefalitis je kompleksna bolest koja zahtijeva multidisciplinarni pristup u dijagnostici i liječenju. Unatoč napretku u dijagnostičkom postupku, veliki broj slučajeva encefalitisa u djece i dalje ostaje etiološki nerazjašnjen.Encephalitis is an inflammatory disease of the brain that can lead to significant disruptions in brain function. It can be classified into infectious and non-infectious, with viruses being the most common pathogen in children. This study aims to provide a descriptive epidemiological analysis of encephalitis cases in children and adolescents treated at the University Hospital for Infectious Diseases "Dr. Fran Mihaljević" between 2006 and 2023. Additionally, it compares the probability of determining the etiology across three different periods, considering the implementation of panels for autoimmune encephalitis diagnostics and multiplex PCR panels for meningitis/encephalitis. The study included data from 243 children and adolescents hospitalized at the Department of Pediatric Infectious Diseases, with an average age of 8 years old. The findings revealed that the etiology was successfully identified in 59.7% of cases. The most common infectious agents were tick-borne encephalitis virus (TBEV) and varicella-zoster virus (VZV), while the most frequent non-infectious encephalitis was acute disseminated encephalomyelitis (ADEM). The analysis indicated that the introduction of new diagnostic methods did not significantly increase the likelihood of identifying the etiology. In conclusion, acute encephalitis is a complex condition requiring a multidisciplinary approach for diagnosis and treatment. Despite advance in diagnostics, a substantial amount of cases remain etiologically unresolved, underscoring the need for ongoing research and improvement in diagnostic strategies
Analysis of HMGB1, RAGE, PCDH1 and Gd-IgA1 in patients with IgA vasculitis
No full textUvod: IgA vaskulitis (IgAV) najčešći je vaskulitis dječje dobi, a obilježava ga sistemska upala u malim krvnim žilama. Obično je povoljnog ishoda, međutim moguće su akutne komplikacije s gastrointestinalnim manifestacijama i nefritis kao kronična, dugoročna komplikacija. Iako su u IgAV-u ispitivani različiti biomarkeri, patogeneza bolesti još uvijek nije poznata niti su poznati biomarkeri koji bi mogli ukazivati na aktivnu bolest i predvidjeti moguća oštećenja.
Ciljevi istraživanja: Ispitati koncentraciju Gd-IgA1, HMGB1, RAGE i PCDH1 u serumu i urinu u djece s IgAV-om i u kontrolnih ispitanika te utvrditi postoji li povezanost s kliničkim značajkama, laboratorijskim nalazima, aktivnosti bolesti i predikcijom pojavnosti nefritisa u djece s IgAV-om.
Ispitanici i metode: Prospektivno istraživanje provedeno je u razdoblju od siječnja 2020. do listopada 2023., a uključilo je 86 djece s IgAV-om i 70 djece iz kontrolne skupine. Koncentracije Gd-IgA1, HMGB1, RAGE i PCDH1 u serumu i urinu određene su imunoenzimskom (ELISA) metodom u akutnoj fazi bolesti i nakon šest mjeseci praćenja u djece s IgAV-om te jednokratno u kontrolnoj skupini.
Rezultati: Koncentracija HMGB1, RAGE i PCDH1 u serumu te koncentracija Gd-IgA1, HMGB1, RAGE i PCDH1 u urinu su statistički značajno veće u djece s IgAV-om nego u kontrolnih ispitanika (p<0,001). U djece s IgAV-om uočena je statistički značajna razlika u vrijednostima koncentracija HMGB1 (5573 pg/ml vs. 3477 pg/ml vs. 1088 pg/ml, p<0,001) i RAGE (309 pg/ml vs. 302,4 pg/ml vs. 201,3 pg/ml, p=0,012) u serumu na početku bolesti u usporedbi s koncentracijom izmjerenom nakon šest mjeseci praćenja te između kontrolne skupine. Regresijska analiza nije izdvojila nijedan od ispitivanih biomarkera kao prediktor nefritisa. Koncentracije Gd-IgA1, HMGB1, RAGE i PCDH1 u urinu su pozitivno korelirale s omjerom albumina i kreatinina u urinu na početku bolesti, a HMGB1, RAGE i PCDH1 i u razdoblju praćenja. Serumska koncentracija RAGE značajno je pozitivno korelirala s koštano-mišićnim manifestacijama IgAV-a (τ=0,185, p=0,030), kao i PCDH1 u urinu (τ=0,238, p=0,012). Logistička regresija izdvojila je serumski Gd-IgA1 (CI 0,943-0,982, p=0,028), RAGE (CI 0,983-0,998, p=0,026) i PCDH1 (CI 1,021-1,137, p=0,012) te HMGB1 u urinu (CI 1,000-1,002, p=0,026) kao prediktore pojavnosti artritisa. Koncentracija HMGB1 u urinu PCDH1 u serumu značajno je pozitivno bila povezana s nalazom mezangijske hipercelularnosti (τ=0,450, p=0,042), a negativno s nalazom endokapilarne hipercelularnosti (τ= -0,478, p=0,030) u bioptiranih bolesnika.
Zaključak: Dobiveni rezultati upućuju na moguću povezanost Gd-IgA1, HMGB1, RAGE i PCDH1 s IgAV-om pri čemu HMGB1 i RAGE pokazuju povišene vrijednosti tijekom praćenja te bi mogli biti pokazatelj aktivnosti bolesti. Ispitivani biomarkeri u ovom istraživanju nisu bili prediktori pojavnosti nefritisa, najvažnije dugoročne komplikacije IgAV-a. Međutim, HMGB1 i PCDH1 mogu imati potencijal u praćenju bolesnika koji su razvili nefritis zbog pozitivne povezanosti s ishodom nefritisa odnosno s nalazom bioptata bubrega.Introduction: IgA vasculitis (IgAV) is the most common childhood vasculitis characterized by systemic inflammation of small blood vessels. It usually has a favorable outcome, however, acute complications with gastrointestinal manifestations and nephritis as chronic, long term complication are possible. Although various biomarkers have been investigated in IgAV, the pathogenesis of the disease is not elucidated yet, nor are known biomarkers that could indicate active disease and predict possible damage.
Objectives: To examine the concentrations of Gd-IgA1, HMGB1, RAGE nad PCDH1 in serum and urine in children with IgAV and in control subjects and to determine whether there is an association with clinical features, laboratory findings, disease activity and prediction of nephritis in children with IgAV.
Subjects and methods: A prospective study was conducted in the period from January 2020 until October 2023, and included 86 children with IgAV and 70 children from the control group. Concentrations of Gd-IgA1, HMGB1, RAGE and PCDH1 in serum and urine were determined by immunoenzymatic (ELISA) method in the acute phase of the disease and after six months follow up interval in children with IgAV and once in the control group.
Results: Concentrations of HMGB1, RAGE and PCDH1 in sera and concentrations of Gd-IgA1, HMGB1, RAGE and PCDH1 in urine were statistically significantly higher in children with IgAV than in the control group (p<0.001). In children with IgAV, a statistically significant difference was observed in concentrations of HMGB1 (5573 pg/mL vs. 3477 pg/mL vs. 1088 pg/mL, p<0.001) and RAGE (309 pg/mL vs. 302.4 pg/mL vs. 201.3 pg/mL, p=0.012) in sera at the onset of the disease compared to the concentration measured after six months follow up and between the control group. Regression analysis didn't reveal any of investigated biomarkers as a predictor of nephritis. Concentrations of Gd-IgA1, HMGB1, RAGE and PCDH1 in urine positively correlated with the urine albumine to creatinine ratio at the onset of the disease, and HMGB1, RAGE and PCDH1 in the follow up interval. Serum RAGE were significantly positively correlated with musculoskeletal manifestations of IgAV (τ=0.185, p=0.030), as well as urinary PCDH1 (τ=0.238, p=0.012). Logistic regression distinguished serum Gd-IgA1 (CI 0.943-0.982, p=0.028), RAGE (CI 0.983-0.998, p=0.026) and PCDH1 (CI 1.021-1.137, p=0.012) and urinary HMGB1 (CI 1.000-1.002, p=0.026) as predictors of the incidence of arthritis. Concentration of HMGB1 in urine was significantly positively correlated with the outcome of nephritis (τ=0.287, p=0.044). Concentration of PCDH1 in the serum was significantly positively correlated with the finding of mesangial hypercellularity (τ=0.450, p=0.042) and negatively with the finding of mesangial hypercellularity (τ= -0.478, p=0.030) in biopsied patients.
Conclusion: Results imply a possible association of Gd-IgA1, HMGB1, RAGE and PCDH1 with IgAV, whereby HMGB1 and RAGE show elevated values during the disease follow up and could be an indicator of disease activity. The investigated biomarkers in this study were not predictors of the occurrence of nephritis, the most important long term complication of IgAV. However, HMGB1 and PCDH1 could have a potential role in the follow up of patients with nephritis due to a positive association with the outcome of nephritis and with the renal biopsy findings