Veterinary medicine - Repository of PHD, master's thesis
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Comparative Targeted Metabolomics of Ischemic Stroke: Thrombi and Serum Profiling for the Identification of Stroke-Related Metabolites
No full textIschemic stroke is one of the leading causes of death and permanent disability in the world. Rapid diagnosis and intervention are crucial for reducing its consequences on individuals and societies. Therefore, identifying reliable biomarkers for early detection, prognostics, and therapy can facilitate the early prediction and prevention of stroke. Metabolomics has been shown as a promising tool for biomarker discovery since many post-ischemic metabolites can be found in the plasma or serum of the patient. In this research, we performed a comparative targeted metabolomic analysis of stroke thrombi, stroke patient serums, and healthy control serums in order to determine the alteration in the patients’ metabolomes, which might serve as biomarkers for early prediction or stroke prevention. The most statistically altered metabolites characterized in the patient serums compared with the control serums were glutamate and serotonin, followed by phospholipids and triacylglycerols. In stroke thrombi compared with the patients’ serums, the most significantly altered metabolites were classified as lipids, with choline-containing phospholipids and sphingomyelins having the highest discriminatory score. The results of this preliminary study could help in understanding the roles of different metabolic changes that occur during thrombosis and cerebral ischemia and possibly suggest new metabolic biomarkers for ischemic stroke
The Impact of Liver Steatosis on Interleukin and Growth Factors Kinetics during Chronic Hepatitis C Treatment
No full textBackground/Objectives: Various biological response modifiers play important roles in the immunopathogenesis of chronic hepatitis C (CHC). While serum levels of cytokines and growth factors change with the disease severity and treatment responses, the impact of concomitant liver steatosis on systemic inflammatory response is largely unknown. The aim of this study was to analyze the characteristics and kinetics of serum profiles of interleukins and growth factors in CHC patients with steatotic liver disease (SLD).
Methods: Serum concentrations of 12 cytokines (IL-5, IL-13, IL-2, IL-6, IL-9, IL-10, IFN-γ, TNF-α, IL-17A, IL-17F, IL-4 and IL-22) and 6 growth factors (Angiopoietin-2, EGF, EPO, HGF, SCF, VEGF) were analyzed in 56 CHC patients at four time points (baseline, week 4, week 8 and SVR12) with bead-based flow cytometry assay.
Results: At baseline, patients with SLD had significantly lower IL-9, IL-10, IL-13 and IL-22 and higher serum concentrations of EGF, VEGF and ANG. In a subgroup of patients with advanced liver fibrosis, SLD was linked with lower serum concentrations of IL-4, IL-5, IL-9, IL-10, IL-13 and IL-22 and higher concentrations of HGH and VEGF. Distinct cytokine kinetics during DAA treatment was observed, and SLD was identified as the main source of variation for IL-5, IL-9, IL-10, IL-13, IL-17A, IL-22, EGF, VEGF and ANG. Patients with SLD at SVR12 had significantly higher VEGF and HGF serum concentrations.
Conclusions: SLD is associated with distinct cytokine and growth factor profiles and kinetics during CHC treatment, which might be associated with disease severity and the capacity for liver regeneration and contribute to fibrosis persistence
Multimodality Imaging of Cardiac Myxomas
No full textCardiac myxomas are the most common benign cardiac neoplasms. Echocardiography is the first-line imaging modality used to analyze cardiac masses, allowing the detection of tumor location, size, and mobility. However, additional imaging techniques are required to confirm the diagnosis, evaluate tissue characteristics of the mass, and assess potential invasion of surrounding structures. Second-line imaging includes cardiac magnetic resonance imaging (MRI) and/or computed tomography (CT) depending on availability and the patient’s characteristics and preferences. The advantages of CT include its wide availability and fast scanning, which allows good image quality even in patients who have difficulty cooperating. MRI has excellent soft-tissue resolution and is the gold standard technique for noninvasive tissue characterization. In some cases, evaluation of the tumor metabolism using 18F-fluorodeoxyglucose positron emission tomography with CT may be useful, mainly if the differential diagnosis includes primary or metastatic cardiac malignancies. A cardiac myxoma can be identified by its characteristic location within the atria, typically in the left atrium attached to the interatrial septum. The main differential diagnoses include physiological structures in the atria like crista terminalis in the right atrium and the coumadin ridge in the left atrium, intracardiac thrombi, as well as other benign and malignant cardiac tumors. In this review paper, we describe the characteristics of cardiac myxomas identified using multimodality imaging and provide tips on how to differentiate myxomas from other cardiac masses
A Novel Time-Aware Deep Learning Model Predicting Myopia in Children and Adolescents
No full textObjective: To quantitatively predict children's and adolescents' spherical equivalent (SE) by leveraging their variable-length historical vision records.
Design: Retrospective analysis.
Participants: Eight hundred ninety-five myopic children and adolescents aged 4 to 18 years, with a complete ophthalmic examination and retinoscopy in cycloplegia prior to spectacle correction, were enrolled in the period from January 1, 2008 to July 1, 2023 at the University Hospital "Sveti Duh," Zagreb, Croatia.
Methods: A novel modification of time-aware long short-term memory (LSTM) was used to quantitatively predict children's and adolescents' SE within 7 years after diagnosis.
Main outcome measures: The utilization of extended gate time-aware LSTM involved capturing temporal features within irregularly sampled time series data. This approach aligned more closely with the characteristics of fact-based data, increasing its applicability and contributing to the early identification of myopia progression.
Results: The testing set exhibited a mean absolute prediction error (MAE) of 0.10 ± 0.15 diopter (D) for SE. Lower MAE values were associated with longer sequence lengths, shorter prediction durations, older age groups, and low myopia, while higher MAE values were observed with shorter sequence lengths, longer prediction durations, younger age groups, and in premyopic or high myopic individuals, ranging from as low as 0.03 ± 0.04 D to as high as 0.45 ± 0.24 D.
Conclusions: Extended gate time-aware LSTM capturing temporal features in irregularly sampled time series data can be used to quantitatively predict children's and adolescents' SE within 7 years with an overall error of 0.10 ± 0.15 D. This value is substantially lower than the threshold for prediction to be considered clinically acceptable, such as a criterion of 0.75 D.
Financial disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article
Respiratory Viruses in Patients With Hematological Malignancy in Boreal Autumn/Winter 2023-2024: EPICOVIDEHA-EPIFLUEHA Report
No full textCommunity‐acquired respiratory viral infections (CARV) significantly impact patients with hematological malignancies (HM), leading to high morbidity and mortality. However, large‐scale, real‐world data on CARV in these patients is limited. This study analyzed data from the EPICOVIDEHA‐EPIFLUEHA registry, focusing on patients with HM diagnosed with CARV during the 2023–2024 autumn–winter season. The study assessed epidemiology, clinical characteristics, risk factors, and outcomes. The study examined 1312 patients with HM diagnosed with CARV during the 2023–2024 autumn–winter season. Of these, 59.5% required hospitalization, with 13.5% needing ICU admission. The overall mortality rate was 10.6%, varying by virus: parainfluenza (21.3%), influenza (8.8%), metapneumovirus (7.1%), RSV (5.9%), or SARS‐CoV‐2 (5.0%). Poor outcomes were significantly associated with smoking history, severe lymphopenia, secondary bacterial infections, and ICU admission. This study highlights the severe risk CARV poses to patients with HM, especially those undergoing active treatment. The high rates of hospitalization and mortality stress the need for better prevention, early diagnosis, and targeted therapies. Given the severe outcomes with certain viruses like parainfluenza, tailored strategies are crucial to improving patient outcomes in future CARV seasons
Influence of genetic polymorphisms of UGT1A4 and UGT2B7 enzymes and ABCB1 and ABCG2 transport proteins on lamotrigine serum concentrations
No full textUvod: Lamotrigin karakterizira značajna interindividualna varijabilnost farmakokinetičkih parametara te je posljedično tome prisutna varijabilnost u učinkovitosti i razvoju štetnih učinaka. Do sada nije razjašnjena uloga polimorfizama metaboličkih enzima UGT1A4 i UGT2B7 te transportnih proteina ABCB1 i ABCG2 na bioraspoloživost lamotrigina.
Svrha: Cilj ovog istraživanja bio je procijeniti razlikuju li se nositelji varijantnog alela UGT2B7 c.-161C>T (rs7668258), UGT1A4*3 c.142T>G (rs2011425), ABCB1 c.1236C>T (rs1128503) i ABCG2 c.421C>A (rs2231142) od odgovarajućih kontrola divljeg tipa (engl. wild type, wt) s obzirom na izloženost lamotriginu.
Metode: U istraživanje su uključeni adolescenti i odrasle osobe s epilepsijom koji su uzimali monoterapiju lamotrigina ili politerapiju lamotrigina i valproata te su bili podvrgnuti rutinskom terapijskom praćenju lijeka. Ispitanici su inače bili zdravi i nisu uzimali druge lijekove koji bi mogli stupiti u interakciju s lamotriginom i valproatom. Uključeni ispitanici genotipizirani su za UGT2B7 c.-161C>T, UGT1A4*3 c.142T>G, ABCB1 c.1236C>T i ABCG2 c.421C>A. Heterozigotni i varijantni homozigotni ispitanici uspoređivani su sa svojim kontrolama divljeg tipa za ostatne koncentracije lamotrigina (standardizirane po dozi)
s prilagodbom prema dobi, spolu, tjelesnoj težini, ostalim ispitivanim polimorfizmima i razinama izloženosti valproatu. Za „ujednačavanje“ vrijednosti kovarijata korišteno je uravnoteživanje entropije.
Rezultati: Uključena je ukupno 471 osoba s epilepsijom, od čega je njih 328 (69.6%) bilo na monoterapiji, a 143 su bili na politerapiji lamotrigina i valproata. Rezultati su pokazali da su nositelji varijantnog alela ABCG2 c.421C>A imali koncentracije lamotrigina niže za 25% u odnosu na kontrole divljeg tipa u slučaju da su ispitanici bili na monoterapiji lamotriginom (valproat 0) ili na kombiniranoj terapiji lamotrigina i valproata (LAM + VAL) ukoliko su koncantracije valproata bile ispod razine kvantifikacije (engl. below the lower limit of quantification, BLOQ). Nije dokazana razlika u koncentracijama lamotrigina između nositelja
varijatnog alela i nositelja divljeg tipa kod ispitanika na kombiniranoj terapiji LAM + VAL ukoliko je koncentracija valproata bila 364 μmol/L [„visok valproat“ - unutar terapijskog raspona ili više (GMR =1.37, 1.03-1.82 frekvencionistička procjena, 1.31, 0.93-1.84, Bayes procjena)]. Nadalje, procijenjen je efekt valproata na dvije razine ABCG2 c.421C>A polimorfizma, tj. u kontrola „divljeg tipa“ i nositelja varijantnog alela. Efekt „visokog valproata“ bio je izraženiji u nositelja varijantnog alela nego u homozigota divljeg tipa (omjer GMR 1.80), kao i efekt „niskog valproata“ (omjer GMR 1.50). Ostatne koncentracije lamotrigina (standardizirane prema dozi) bile su podjednake u nositelja varijantnih alela i kontrola divljeg tipa za UGT2B7 c.-161C>T, UGT1A4*3 c.142T>G i ABCB1 c.1236C>T.
Zaključak: Rezultati istraživanja sugeriraju da polimorfizam ABCG2 c.421C>A moderira učinak valproata na izloženost lamotriginu, dok polimorfizmi UGT2B7 c.-161C>T, UGT1A4*3 c.142T>G i ABCB1 c.1236C>T nemaju relevatnog učinka na bioraspoloživost lamotrigina u osoba s epilepsijom.Introduction: Lamotrigine is characterized by significant interindividual variability in pharmacokinetic parameters and, consequently, there is variability in efficacy and the risk for adverse reactions. The role of polymorphisms of UGT1A4 and UGT2B7 metabolic enzymes as well as ABCB1 and ABCG2 transport proteins on the lamotrigine bioavailability has not
yet been clarified.
Purpose: To estimate whether epilepsy patients with variant UGT2B7 c.-161C>T (rs7668258), UGT1A4*3 c.142T>G (rs2011425), ABCB1 c.1236C>T (rs1128503) and ABCG2 c.421C>A (rs2231142) alleles differ from their wild-type (wt) peers in exposure to lamotrigine.
Methods: Consecutive adults on lamotrigine monotherapy or lamotrigine and valproate cotreatment undergoing routine therapeutic drug monitoring, otherwise generally healthy and free of interacting drugs, were genotyped for UGT2B7 -161C>, UGT1A4*3 c.142T>G, ABCB1 c.1236C>T (rs1128503) and ABCG2 c.421C>A. Heterozygous and variant homozygous subjects were compared to their wt controls for dose-adjusted lamotrigine troughs with adjustment for age, sex, body weight, other evaluated polymorphisms, and level of exposure to valproate using covariate entropy balancing.
Results: Of the 471 included patients, 328 (69.6%) were on monotherapy and 143 were cotreated with valproate. The results showed that c.421C>A variant allele carriers had by 25% lower lamotrigine concentrations compared to wild-type controls if the subjects were on lamotrigine monotherapy or lamotrigine and valproate (LAM + VAL) polytherapy if valproate troughs were below the lower limit of quantification (BLOQ). Variant c.421C>A allele had no obvious effect on lamotrigine troughs if valproate concentrations were 364 μmol/L [target/high valproate (GMR =1.37, 1.03-1.82 frequentist; 1.31, 0.93-1.84, Bayesian)]. Furthermore, we evaluated the effect of valproate on two levels of the ABCG2 c.421C>A polymorphism ("wild type" controls and variant allele carriers). The "high valproate" effect was more pronounced in the variant allele carriers than in the wild-type homozygotes (GMR ratio 1.80), as was the "low valproate" effect (GMR ratio 1.50). Dose-adjusted lamotrigine troughs in UGT2B7 c.-161C>T, UGT1A4*3 c.142T>G and ABCB1 c.1236C>T variant allele carriers were closely similar to those in their wt controls.
Conclusion: Data suggests that ABCG2 c.421C>A polymorphism moderates the effect of valproate on exposure to lamotrigine, while dose-adjusted lamotrigine troughs in epilepsy patients with variant UGT2B7 c.-161C>T, UGT1A4*3 c.142T>G or ABCB1 c.1236C>T alleles are equivalent to those in their respective wt peers
Asthma comorbidities
No full textAstma je ozbiljan globalni zdravstveni problem koji utječe na sve dobne skupine. Trenutačno diljem svijeta raste prevalencija i incidencija astme te se iz istog razloga sve više pažnje pridaje liječenju astme. Prevalencija astme raste u pedijatrijskoj dobi što može izazvati doživotne probleme u oboljelih i smanjiti kvalitetu života. Astma se može prezentirati raznim kliničkim slikama, u najčešće simptome se uključuju piskutanje, zaduha, stezanje u prsima te kašalj. Svi ovi simptomi variraju i u vremenu i u intenzitetu. Bitno je pravovremeno dijagnosticirati astmu kako bi se pravovremeno pristupilo njenome liječenju, no isto tako kako bi se mogli pristupiti i liječenju njenih komorbiditeta. U slabije kontroliranim oblicima naposljetku može nastupiti i perzistentna opstrukcija protoku zraka. Zbog njene kroničnosti, komorbiditeti su česti te se primarno dijele na plućne i izvanplućne. Najčešći komorbiditeti respiratornog trakta su alergijski rinitis, kronični rinosinusitis s ili bez nosnih polipa, opstruktivna apneja u snu, disfunkcija glasnica, disfunkcionalno disanje, kronična opstruktivna plućna bolest te bronhiektazije. Najčešći ekstrapulmonarni komorbiditeti su gastroezofagealna refluksna bolest, pretilost, kardiovaskularne bolesti, psihički poremećaji te alergija na hranu i anafilaksa. Važno je pravovremeno prepoznati komorbiditete i pristupiti njihovom liječenju iz više razloga, od kojih su neki: 1) komorbiditeti mogu biti odgovorni za pogoršanje astme; 2) komorbiditeti mogu biti dio istog patofiziološkog puta; 3) komorbiditeti se mogu ponašati kao faktori zabune; 4) komorbiditeti mogu smanjivati kvalitetu života u osobe smanjenjem efikasnosti liječenja ili smanjenim pridržavanja liječenja; 5) komorbiditeti povećavaju rizik za razvoj težih komorbiditeta. Svakome se komorbiditetu mora pristupiti zasebno, a vrlo često zahtijevaju razmatranje multidisciplinarnoga tima zbog njihove kompleksnosti.Asthma is a serious global health problem that affects all age groups. Currently, the prevalence and incidence of asthma are increasing worldwide, leading to increased attention to asthma treatment. The growing prevalence of asthma in pediatric age groups is becoming a significant problem, often resulting in lifelong issues and reduced quality of life. Asthma can present with various clinical pictures but is most commonly associated with wheezing, shortness of breath, chest tightness, and coughing. These symptoms vary in time and intensity. In poorly controlled forms, chronic airflow obstruction can eventually occur. It is essential to diagnose asthma promptly to initiate timely treatment, but also to address the treatment of its comorbidities. Due to its chronic nature, comorbidities are relatively common in individuals with asthma, primarily divided into pulmonary and extrapulmonary comorbidities. The most common comorbidities of the respiratory tract include allergic rhinitis, chronic rhinosinusitis with or without nasal polyps, obstructive sleep apnea, vocal cord dysfunction, dysfunctional breathing, chronic obstructive pulmonary disease, and bronchiectasis. The most common extrapulmonary comorbidities include gastroesophageal reflux disease, obesity, cardiovascular diseases, psychiatric disorders, and food allergy and anaphylaxis. It is important to recognize comorbidities promptly and initiate their treatment for several reasons, including: 1) they may exacerbate asthma; 2) they may be part of the same pathophysiological pathway; 3) they may act as confounding factors; 4) they may reduce the quality of life by reducing the effectiveness of treatment or reducing treatment adherence; 5) they may increase the risk of developing more severe comorbidities. Each comorbidity must be addressed individually with the help of a multidisciplinary team due to their complexity
Efficacy of post-transplant cyclophosphamide in the prevention of graft-versus-host disease following allogeneic hematopoietic stem cell transplant from an unrelated mismatched donor
No full textTransplantacija hematopoetskih matičnih stanica potencijalno je kurativna metoda liječenja različitih hematoloških i nehematoloških bolesti. Za život opasna bolest darivatelja protiv primatelja jedna je od glavnih komplikacija transplantacije hematopoetskih matičnih stanica. Poslijetransplantacijski ciklofosfamid (PTCy) uspješno se koristi kao profilaksa bolesti darivatelja protiv primatelja (GVHD) nakon haploidentične transplantacije hematopoetskih matičnih stanica, a istraživanja pokazuju kako se njegovo profilaktično djelovanje očituje i u alogeničnoj transplantaciji, premošćujući HLA-barijeru. U svrhu ispitivanja učinkovitosti poslijetransplantacijskog ciklofosfamida nakon alogenične transplantacije od nesrodnog nepodudarnog darivatelja provedena je retrospektivna studija primatelja alogenične transplantacije KBC-a Zagreb između siječnja 2020. te lipnja 2023. Izdvojen je 161 pacijent, od kojih je je 120 primilo transplantaciju od nesrodnog podudarnog darivatelja, a 41 od nesrodnog nepodudarnog darivatelja. 21 pacijent primio je transplantaciju od nesrodnog nepodudarnog darivatelja te PTCy. Uspoređeni su parametri GVHD-a između nepodudarne skupine koja je primila PTCy te nepodudarne (nePTCy 9/10) i podudarne (nePTCy 10/10) skupine koje nisu primile PTCy. Sveukupni udio slučajeva akutnog GVHD-a (aGVHD-a) bio je najniži u skupini pacijenata koji su primili PTCy (n=4, 19%), u odnosu na nepodudarnu (n=8, 40%) i podudarnu nePTCy skupinu (nePTCy 10/10, n=41, 34,5%). Sveukupni udio slučajeva kroničnog GVHD-a (cGVHD-a) bio je najniži u podudarnoj nePTCy skupini (n=21, 17,65%), zatim u PTCy skupini (n=4, 19%) te u nepodudarnoj nePTCy skupini (n=4, 20%). Ovim istraživanjem dobiveni su preliminarni podaci koji upućuju na potencijalno zaštitno djelovanje PTCy u profilaksi GVHD-a, međutim ne postiže se statistička značajnost (p>0.05) te je potrebno daljnje istraživanje s više ispitanika te podrobnija statistička analiza kako bi se potvrdili ovi nalazi.Hematopoietic stem cell transplantation is a potentially curative treatment method for various hematologic and non-hematologic diseases. The life-threatening graft-versus-host disease is one of the main complications of hematopoietic stem cell transplantation. Post-transplantation cyclophosphamide (PTCy) is successfully used as graft-versus-host disease (GVHD) prophylaxis after haploidentical stem cell transplantation, but research shows its effect in allogeneic stem cell transplantation, crossing the HLA-barrier. To examine the efficacy of post-transplantation cyclophosphamide after allogeneic stem cell transplantation from a mismatched unrelated donor, a retrospective study was conducted on allogeneic stem cell transplantation recipients between January 2020 and June 2023 at the University Hospital Center Zagreb. 161 patients were identified, from which 120 received transplantation from a matched unrelated donor, and 41 from a mismatched unrelated donor. 21 patients received an allogeneic stem cell transplantation from a mismatched unrelated donor and also received PTCy. GVHD parameters were compared between the mismatched group that received PTCy and the mismatched (nonPTCy 9/10) and matched (nonPTCy 10/10) groups that have not received PTCy. The overall proportion of acute GVHD cases was the lowest in the group that received PTCy (n=4, 19%), in comparison to the mismatched (n=8, 40%) and matched nonPTCy groups (n=41, 34,5%). The overall proportion of chronic GVHD cases was the lowest in the matched nonPTCy group (n=21, 17,65%), followed by the PTCy group (n=4, 19%) and the mismatched nonPTCy group (n=4, 20%). This study yielded preliminary findings suggesting a potentially protective effect of PTCy as GVHD prophylaxis, but without reaching statistical significance (p>0.05). Further research with more subjects and more thorough statistical analysis is needed to confirm these findings
Antinuclear antibodies in juvenile idiopathic arthritis
No full textIvana Sabljak: Antinuklearna protutijela u juvenilnom idiopatskom artritisu
Uvod: Juvenilni idiopatski artritis (JIA) je kronična reumatska bolest, nepoznatog uzroka, koja
pogađa djecu u dobi do 16. godina, s prevalencijom od 1 – 2 / 1000 djece. Sukladno trenutno
važećoj klasifikaciji, bolest se dijeli u 7 različitih tipova. U sklopu dijagnostičke obrade određuju
se i antinuklearna protutijela (ANA) čiji pozitivni nalaz češći u pojedinim tipovima bolesti i primarno
ukazuje na povećani rizik razvoja kroničnog uveitisa. Standardizirani ANA obrasci određeni
metodom indirektne imunoflorescencije (IIF) na humanim epitelnim stanicama tipa 2 (Hep-2)
predstavljaju daljnji napredak u dijagnostici različitih autoimunosnih bolesti.
Ciljevi istraživanja: Utvrditi postoji li povezanost specifičnih ANA obrazaca s pojedinim tipovima
JIA i kroničnim uveitisom u sklopu osnovne bolesti. Dodatno su istražene demografske i kliničke
osobitosti bolesnika s JIA.
Metode: U retrospektivno istraživanje uključeni su svi bolesnici s dijagnozom JIA, praćeni u
reumatološkoj ambulanti Zavoda za kliničku imunologiju, respiracijske i alergološke bolesti i
reumatologiju Klinike za pedijatriju Kliničkog bolničkog centra Zagreb u periodu od rujna 2023 do
svibnja 2024. Pregledom medicinske dokumentacije prikupljeni su podaci o dobi bolesnika na
početku bolesti, spolu bolesnika, razvoju uveitisa, nalazu ANA te utvrđenim ANA obrascima.
Rezultati: U istraživanje je uključen 71 bolesnik s dijagnozom JIA. Gotovo 2/3 bolesnika bilo je
ženskog spola (60,6 %), u najvećeg broja bolesnika JIA je počeo u dobi između 12 - 24 mjeseca.
Najčešći tip JIA bio je oligoartikularni (oJIA) (53.5 %), dok je sistemski tip (sJIA) bio najmanje
zastupljen (8.5 %). Glavnina između 40 bolesnika s pozitivnim nalazom ANA bila je ženskog
spola, predškolske dobi, s oJIA tipom bolesti. Kronični uveitis registriran je u 8 bolesnika, od čega
je 7 imalo pozitivni nalaz ANA. ANA (AC) obrasci su određeni u 26 bolesnika među kojima je 20
bolesnika imalo 1, a 6 bolesnika 2 AC obrasca. Statistički značajna povezanost utvrđena je
između AC-1 obrasca i oJIA. Nije utvrđena povezanost AC-1 niti drugih obrazaca s drugim
tipovima bolesti niti razvojem kroničnog uveitisa. Analiza povezanosti AC obrazaca i spola
bolesnika pokazuje tendenciju češće pojavnosti AC-1 obrasca u djevojčica, generalno nije
utvrđena statistički značajna povezanost AC obrazaca i spola bolesnika.
Zaključak: Istraživanje provedeno na ograničenom uzorku bolesnika s JIA utvrdilo je statistički
značajnu povezanost AC-1 obrasca i oJIA tipa bolesti te time djelomično potvrdilo hipotezu o
povezanosti specifičnih AC obrazaca s pojedinim tipovima JIA. Potrebna su daljnja,
sistematizirana istraživanja, uz korelaciju AC obrazaca s većim brojem demografskih, kliničkih i
laboratorijskih karakteristika velikog broja bolesnika kako bi se utvrdila njihova definitivna
vrijednosti kao samostalnog parametra ili elementa statističkih modela za pretkazivanja ishoda
JIA i rizika razvoja uveitisa.Ivana Sabljak: Antinuclear antibodies in juvenile idiopathic arthritis
Introduction: Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease of unknown cause
that affects children up to the age of 16 years, with a prevalence of 1-2/1000 children. According
to the currently valid classification, the disease can be divided into 7 different types. As part of
diagnostic evaluation, the antinuclear antibody (ANA) test is usually performed, and a positive
result is associated with an increased risk of chronic uveitis. Standardised AC patterns determined
by indirect immunofluorescence (IIF) on human epithelial cells type 2 (Hep-2) represent further
progress in the diagnosis of various autoimmune diseases.
Aim: The study aims to identify particular ANA patterns linked with specific types of JIA and
chronic uveitis. The demographic and clinical characteristics of patients with JIA were additionally
investigated.
Methods: From September 2023 to May 2024, patients with a diagnosis of JIA followed in the
rheumatology outpatient clinics of the Division of Clinical Immunology, Respiratory and
Allergology Diseases and Rheumatology of Paediatric Department of Clinical Hospital Centre
Zagreb were included in the retrospective study. The patients' medical records were examined to
obtain information on age at disease onset, gender, occurrence of uveitis, ANA test results, and
specific ANA patterns.
Results: A total of 71 patients diagnosed with JIA were included in the study. Almost 2/3 of the
patients were females (60.6%). In the largest number of patients, JIA started between the ages
of 12 and 24 months. The most common type was oligoarticular (oJIA) (53.5%), whereas the
systemic type (sJIA) was the least common (8.5 %). The majority of the 40 patients with a positive
ANA result were females, of preschool age and with oJIA type of disease. Chronic uveitis was
registered in 8 patients, of which 7 had a positive ANA test. ANA (AC) patterns were determined
in 26 patients, among whom 20 and 6 patients had 1 and 2 AC patterns, respectively. A statistically
significant association was established between the AC-1 pattern and oJIA. The association
between AC1 and other patterns and the development of chronic uveitis has not been established.
The analysis of the association between AC patterns and gender sex revealed that the AC1
pattern occurs more frequently in female patients. In general, no statistically significant
association between the AC patterns and the patient's gender was established.
Conclusion: The significant association between the AC-1 pattern and oJIA type of JIA, as
identified through research on a limited patient sample, partially supports the hypothesis linking
specific ANA patterns to certain types of JIA. To determine the value of AC patterns as an
independent predictor of JIA and uveitis outcomes, larger-scale research is warranted to explore
their correlation with demographic, clinical, and laboratory variables
Use of health information system: a comparison of two models of reference price systema
No full textOdređivanje referentnih cijena lijekova jedna je od mjere snižavanja cijena lijekova i kontrole rasta zdravstvene potrošnje. Uporabom zdravstvenoinformacijskog sustava napravljena je usporedba modela određivanja referentnih cijena lijekova na ATK razini III-V i ATK razini V kako bi se prikazali mogući financijski učinci provedbe jednog ili drugog modela.
Određivanje referentnih cijena lijekova u Hrvatskoj se provodi na ATK razini III-V. Na modelu određivanja referentnih cijena lijekova provedenom 2012. godine na ATK razini III-V napravljen je usporedni model određivanja referentnih cijena lijekova na ATK razini V. Navedena dva modela su uspoređena na osnovi projekcije moguće uštede vezano uz provedbu jednog ili drugog modela.
Projekcija moguće uštede napravljena je na osnovi potrošnje lijekova u godini koja je prethodila postupku određivanja referentnih cijena. Primjenom modela određivanja referentnih cijena lijekova na ATK razini III-V procijenjena ušteda bi iznosila 318.398.149,58 kn dok bi primjenom modela određivanja referentnih cijena lijekova na ATK razini V procijenjena uštede bi iznosila 254.451.262,30 kn.
Prikazana je korisnost primjene zdravstvenoinformacijskog sustava u svakodnevnom radu u procesu donošenje odluka vezano uz odabir modela određivanja referentnih cijena lijekova. Primjenom modela određivanja referentnih cijena lijekova na ATK razini III-V moguće je postići veću uštedu u odnosu na model koji se provodi ATK razini V.A determination of referent prices of drugs is one of measures of the pharmaceutical costs reduction and control of total health costs. In order to present financial effects of the application of the model of reference price system at the Anatomical Therapeutic Chemical Classification System (ATC) III-V level and the model of reference price system at ATC V level, a comparative analysis of those two models has been performed using health information system.
In Croatia, the model of reference price system at ATC III-V level has been applied. For the model of reference price system at ATC III-V level, applied in 2012, a comparative model of reference price system at ATC V level has been performed. Those two models have been compared based on the financial benefits projection related to their application. Financial benefits projection has been made based on the drug expenditure in the year that preceded a price referencing year.
Financing benefits projection using the model of reference price system at ATC III-V level has been estimated on 318.398.149,58 HRK, whereas financing benefits projection using the model of reference price system at ATC V level has been estimated on 254.451.262,30 HRK.
Benefits of the use of health information system in a reference price system, related to selection of the best price referencing model, have been presented. Financial benefits using the price referencing system model on the ATC III-V level seemed to be greater than using the price referencing system model on the ATC V level