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A Comprehensive Analysis of Renal and Endothelium Dysfunction Markers Fourteen Years after Hemorrhagic Fever with Renal Syndrome Contraction
No full textWhile the pathology of acute hemorrhagic fever with renal syndrome (HFRS) has been widely researched, details on the chronic HFRS sequelae remain mainly unexplored. In this study, we analyzed the clinical and laboratory characteristics of 30 convalescent HFRS patients 14 years after the disease contraction, mainly emphasizing several endothelial dysfunction parameters. Convalescent HFRS patients exhibited significantly higher serum levels of erythrocyte sedimentation rate, von Willebrand factor, uric acid, C-reactive protein and immunoglobulin A when compared to healthy individuals. Furthermore, 24 h urine analyses revealed significantly lower sodium and potassium urine levels, as well as significantly higher proteinuria, microalbumin levels and β2-microglobulin levels when compared to healthy individuals. First morning urine analysis revealed significantly higher levels of hematuria in convalescent HFRS patients. None of the additional analyzed endothelium dysfunction markers were significantly different in post-HFRS patients and healthy individuals, including serum and urine P-selectin, E-selectin, soluble intercellular adhesion molecule 1, vascular intercellular adhesion molecule 1 (sVCAM-1) and vascular endothelial growth factor (VEGF). However, binary logistic regression revealed a weak association of serum sVCAM-1 and urine VEGF levels with HFRS contraction. Generally, our findings suggest mild chronic inflammation and renal dysfunction levels in convalescent HFRS patients 14 years after the disease contraction
Pancreatic Iodine Density and Fat Fraction on Dual-Energy Computed Tomography in Acute Pancreatitis
No full textThe aim of our study was to investigate iodine density (ID) and fat fraction (FF) on dual-energy computed tomography (DECT) in patients with acute pancreatitis (AP). This retrospective study included 72 patients with clinically confirmed AP and 62 control subjects with DECT of the abdomen. Two radiologists assessed necrosis and measured attenuation values, ID, and FF in three pancreatic segments. We used receiver operating characteristic (ROC) analysis to determine the optimal threshold for ID for the differentiation between AP groups. The ID was significantly higher in interstitial edematous AP compared to necrotizing AP and the control group (both p 0.05) for the head, body, and tail, respectively. The FF was significantly higher for pancreatitis groups when compared with the control group in the head and body segments (both p < 0.001). In the tail, the difference was significant in necrotizing AP (p = 0.028). The ID values were independent of attenuation values correlated with the FF values in pancreatic tissue. Iodine density values allow for differentiation between morphologic types of AP
Istraživanje molekularnih i funkcionalnih svojstava glavnih regulatora aktivnosti stanica NK
No full textObjectives: Natural killer (NK) cells are part of innate immunity and play an important role in early immunological defense against different types of infections as well as tumors. On their cell surface they express a range of activating and inhibitory receptors through which they can eliminate potentially dangerous cells while sparing healthy ones. It is believed that NK cell activation is achieved by shifting the balance of signals, received through activating and inhibitory receptors, towards activation. However, recently it has been questioned whether this system is sensitive enough, and if there is an additional requirement for a “master signal” to reach full NK cell activity. Our hypothesis is that CD16, NKG2D and NCR1 are these “master regulators”, whose triggering is essential for NK cells to gain full activation, and our objective was to investigate the dependence of NK cell activation on these three receptors. Materials and methods: Triple knock out (TKO) mice lacking CD16, NKG2D and NCR1 receptors were generated. Phenotypic analysis of NK cells was done in the spleen, bone marrow, kidney, liver and blood of mice. To determine the impact of triple deficiency on the functionality of NK cells in vitro, proliferation assay as well as stimulations with different cytokines and through different receptors, were done. Using various tumor targets, killing capacity as well as cytokine production of TKO NK cells was analyzed in co-cultivation assay. Next, mice were inoculated with RMA-S lymphoma and B16 melanoma to test the functionality of TKO NK cells in vivo. Furthermore, B16 tumor infiltrating NK cells (TANKs) were analyzed. To investigate how TKO mice control viral infections a model of murine cytomegalovirus (mCMV) was used. Finally, to confirm that the findings were NK cell intrinsic, we generated and analyzed mixed bone marrow chimeras. Results: Phenotypic analysis revealed a more mature phenotype of NK cells in the periphery, whereas there were no changes in the number and frequency of NK cells. Alternations in the receptor expression as well as hyper-responsiveness through NK1.1 receptor were present. In vitro killing of RMA-S, B16 and YAC-1 tumor targets was comparable to the wild type controls, while in vivo TKO mice had a significant defect in the control of B16 melanoma. Analysis of B16 TANKs revealed that TKO NK cells were less activated and produced lower amounts of Perforin and IFNγ. The latter is known to be an important cytokine for the control of B16 melanoma. mCMV
infection resulted in higher viral titers in the lungs and spleen, indicating a compromised control of mCMV. Conclusion: Although the results of this work show that CD16, NKG2D and NCR1 receptors are not the “master regulators” of NK cell activity, the analysis of TKO mice revealed incredible compensatory mechanisms of NK cells. The lack of three important activating receptors: CD16, NKG2D and NCR1 results in worse control of viral infection, as well as certain tumors, but this deficiency is mostly compensated, so the development and activation of NK cells is largely comparable to that of control animals. The observed compensation is a result of change in the level of expression as well as the activity of individual receptors on NK cells. The obtained knowledge provides a deeper insight into the biology of NK cells, indicating their incredible plasticity and ability to compensate, which can potentially be useful in the further development of NK cell dependent immunotherapieCiljevi: Stanice prirodne ubojice (NK) dio su urođenog imuniteta i igraju važnu ulogu u ranoj imunološkoj obrani od različitih vrsta infekcija, kao i tumora. Na svojoj površini izražaju niz aktivacijskih i inhibicijskih receptora putem kojih mogu eliminirati potencijalno opasne stanice, a poštedjeti zdrave. Trenutna dogma nalaže da se aktivacija stanica NK postiže pomicanjem ravnoteže signala, primljenih preko aktivacijskih i inhibicijskih receptora, prema aktivaciji. Međutim, javlja se pitanje dovoljne osjetljivosti ovog sustava te postoji li dodatna potreba za “glavnim signalom” za postizanje potpune aktivnosti stanica NK. Naša hipoteza je da su CD16, NKG2D i NCR1 ti "glavni regulatori", čije je aktiviranje ključno, a cilj nam je bio istražiti ovisnost aktivacije stanica NK o ova tri receptora. Materijali i metode: Generirani su miševi kojima nedostaje izražaj CD16, NKG2D i NCR1 receptora (TKO miševi). Fenotipska analiza stanica NK učinjena je na stanicama izoliranima iz slezene, koštane srži, bubrega, jetre i krvi miševa. Kako bi se utvrdio utjecaj trostrukog nedostatka na funkcionalnost stanica NK in vitro, napravljen je test proliferacije kao i stimulacije različitim citokinima te putem različitih receptora. Korištenjem različitih tumorskih staničnih linija u testu kokultivacije, analizirana je sposobnost ubijanja kao i proizvodnja citokina od strane TKO stanica NK. Kako bi se testirala funkcionalnost stanica NK in vivo, miševi su inokulirani s limfomom RMA-S i melanomom B16. Analizirane su B16 tumor infiltrirajuće stanice NK (TANKs). Da bismo istražili kako TKO miševi kontroliraju virusne infekcije, korišten je model mišjeg citomegalovirusa (mCMV). Konačno, kako bismo potvrdili da su saznanja intrinzična za stanice NK, generirali smo i analizirali kimere miješane koštane srži. Rezultati: Analiza fenotipa pokazala je zreliji fenotip stanica NK na periferiji, dok promjena u broju i frekvenciji stanica NK nije bilo. Prisutne su bile promjene u ekspresiji receptora kao i hiper-reaktivnost receptora NK1.1. In vitro ubijanje RMA-S, B16 i YAC-1 tumorskih meta bilo je usporedivo s kontrolama divljeg tipa, dok su in vivo miševi TKO pokazali značajan nedostatak u kontroli melanoma B16. Analiza TANK B16 otkrila je da su TKO stanice NK manje aktivirane te da proizvode manje količine perforina i IFNγ. Poznato je da je potonji citokin važan za kontrolu melanoma B16. Infekcija mCMV-om rezultirala je višim titrom virusa u plućima i slezeni, što ukazuje na oslabljenu kontrolu mCMV-a. V Zaključak: Iako rezultati ovoga rada pokazuju da receptori CD16, NKG2D i NCR1 nisu “glavni regulatori” aktivnosti stanica NK, analiza miševa TKO otkrila je nevjerojatnu razinu kompenzacijskih mehanizama stanica NK. Nedostatak tri važna aktivacijska receptora: CD16, NKG2D i NCR1 rezultira lošijom kontrolom virusne infekcije, kao i određenih tumora, no ipak ovaj nedostatak većinom biva kompenziran te su razvoj i aktivacija stanica NK uvelike usporedivi s onima kontrolnih životinja. Uočena kompenzacija posljedica je promjene u razini ekspresije kao i aktivnosti pojedinih receptora na stanicama NK. Dobivena saznanja daju dublji uvid u biologiju stanica NK, ukazujući na njihovu nevjerojatnu plastičnost i sposobnost kompenzacije, što potencijalno može biti korisno u daljnjem razvoju imunoterapija ovisnih o stanicama NK
PREVALENCE, Characteristics, and Awareness of Chronic Kidney Disease in Croatia: The EH-UH 2 Study
No full textBackground. National surveys have reported variable prevalence of chronic kidney disease (CKD), due to differences in the characteristics of the population, study design, equations used for the estimated glomerular filtration rate (eGFR), and definitions. The EH-UH 2 survey is the first study evaluating CKD prevalence, characteristics, and awareness in Croatia. Methods. This was a cross-sectional nationwide observational study designed to assess the prevalence of CKD and cardio–kidney–metabolic risk factors in Croatia, which included 1765 randomly selected subjects. We estimated the prevalence of CKD by means of the albumin-to-creatinine ratio (ACR) and eGFR (CKD-EPI equation). Comorbidities and anthropometric and social factors related to the prevalence of CKD were analyzed, and the CV risk profile was evaluated. Results. The weighted prevalence of CKD (any stage), CKD stage ≥G3A A2, and CKD defined only as an eGFR 30 mg/g was 15.1%. Older age, male gender, diabetes, ePWV, and uric acid were independently associated with CKD prevalence. The awareness of CKD was 9.5%. Persons unaware of CKD were older with lower income, less education, more frequent diabetes, hypertension (less frequently controlled), and milder renal impairment. Conclusions. In Croatia, the estimated prevalence of CKD is high, being presented more frequently in men than in women. CKD patients have an unfavorable CV risk profile. The awareness of CKD is very low, reflecting poor health literacy in the general population but also in health-care workers
Comprehensive Characterization of Anti-HLA and Non-HLA Antibodies in Patients on Kidney Transplant Waiting List and Evaluation of Their Impact on Alloimmunization Risk and Dialysis Treatment
No full textAlloimmunization remains a major obstacle to successful kidney transplantation, mainly due to the formation of anti-HLA antibodies. In recent years, non-HLA antibodies have emerged as additional immunologic factors that can potentially contribute to graft rejection. The aim of this study was to investigate the prevalence and specificity of both anti-HLA and non-HLA antibodies in patients with end-stage renal disease on a waiting list for kidney transplantation. Serum samples from 74 patients were analyzed using complement-dependent cytotoxicity and solid-phase assays. IgG anti-HLA antibodies were identified in 43.2% of participants, while IgG non-HLA antibodies were detected in 91.9%. The most frequent non-HLA antibodies included anti-ENO1 (28.4%), anti-FIBR1 (23.0%) and anti-PRKCZ (23.0%). A significant difference was found between the number of distinct IgG anti-HLA and IgG non-HLA antibody specificities. However, no significant correlation was found between the number of IgG non-HLA antibody specificities and previous alloimmunization events or dialysis treatments. These results suggest that non-HLA antibodies, although often overlooked, can sometimes play a critical role in transplant outcomes. Routine testing for non-HLA antibodies, in addition to mandatory anti-HLA antibody screening and identification, could improve immunologic risk assessment in transplant patients and post-transplant care
Croatian Action on Salt and Health (CRASH): On the Road to Success—Less Salt, More Health
No full textThe World Health Organization recommends adjusting salt intake as a part of the nine global targets to reduce premature mortality from non-communicable chronic diseases as a priority and the most cost-effective intervention. In 2006, the main aim of the Croatian Action on Salt and Health was to decrease salt intake by 16% because of its critical intake and consequences on human health. We have organized educative activities to increase awareness on salt harmfulness, define food categories of prime interest, collaborate with industries and determine salt intake (24 h urine sodium excretion). It was determined that the proportion of salt in ready-to-eat baked bread should not exceed 1.4%. In the period 2014–2022, salt in semi-white bread was reduced by 14%, 22% in bakery and 25% in the largest meat industry. Awareness of the harmfulness of salt on health increased from 65.3% in 2008 to 96.9% in 2023 and salt intake was reduced by 15.9–1.8 g/day (22.8% men, 11.7% women). In the last 18 years, a significant decrease in salt intake was achieved in Croatia, awareness of its harmfulness increased, collaboration with the food industry was established and regulatory documents were launched. However, salt intake is still very high, underlying the need for continuation of efforts and even stronger activities
Radial artery – vascular approach in diagnostic coronarography and percutaneous coronary interventions
No full textPopularnost radijalnog vaskularnog pristupa počela je rasti nakon što ga je 1989. u svom radu
opisao L. Campeau. Prije punkcije radijalne arterije potrebno je izvesti testove kolateralne
cirkulacije kroz šaku. To su modificirani Allenov test i Barbeau test. Postoje dva načina
pristupa radijalnoj arteriji: mikropunkcijska tehnika te Seldingerova tehnika. Radijalna arterija
kao vaskularni pristup može se koristiti u dijagnostičkim koronarografijama, prekutanim
koronarnim inetrvencijama, neurointervencijama, za formaciju arteriovenske fistule i kao
premosnica koronarnih krvnih žila. Zbog površnog toka radijalne arterije moguća je relativno
laka hemostaza te su zbog toga komplikacije, kao što je veliko krvarenje, rjeđe nego kada se
pristupa femoralno. Komplikacije radijalnog pristupa dijele se na intra-proceduralne i postproceduralne. Intra-proceduralne komplikacije su spazam radijalne arterije, perforacija i kompartment sindrom te disekcija. Post-proceduralne komplikacije su okluzija radijalne arterije, hematom i pseudoaneurizma. Novije mjesto pristupa kroz radijalnu arteriju nalazi se
distalno, na tzv. anatomskom snuffboxu. Ukoliko se ne može pristupiti radijalnoj arteriji,
moguća je konverzija na ulnarni ili femoralni vaskularni pristup. Radijalni pristup je 2022.
godine postao zlatni standard za PCI.The popularity of the radial vascular approach began to grow after L. Campeau described it in
his article in 1989. Before the puncture of the radial artery, it is necessary to perform
collateral circulation tests through the hand. Those thests are modified Allen test and the
Barbeau test. There are two ways of accessing the radial artery. The micropuncture technique
and the Seldinger technique. The radial artery as a vascular access can be used in diagnostic
coronary angiography, percutaneous coronary interventions (PCI), neurointerventions, for the
formation of arteriovenous fistula and as a bypass of coronary arteries. Due to the superficial
course of the radial artery, relatively easy haemostasis is possible, and as a result,
complications such as major bleeding are less common than when the femoral approach is
performed. Radial access complications are divided into intra-procedural and post-procedural.
Intra-procedural complications are spasm of the radial artery, perforation and compartment
syndrome and dissection. Post-procedural complications are radial artery occlusion,
hematoma and pseudoaneurysm. The newer point of access through the radial artery is located
distally, at the so-called anatomical snuffbox If the radial artery cannot be accessed,
conversion to ulnar or femoral vascular access is possible. In 2022, the radial approach
became the gold standard for PCI
Role of IgM enriched Immunoglobulins in children with sepsis in Clinical Hospital Center Rijeka - retrospective study
No full textSepsa je kao jedan od najčešćih dijagnostičko-terapijskih izazova uzrok značajnog morbiditeta i mortaliteta kod novorođenčadi i starije djece. Osim standardnog antibiotskog liječenja, brojna istraživanja su posvećena proučavanju kliničke učinkovitosti imunoglobulina obogaćenog IgM u liječenju sepse.
Cilj ovog istraživanja bio je analizirati bolesnike koji su primali IgM obogaćenog intravenoznog imunoglobulina [IgM-IVIG] kao pomoćne farmakoterapije sepse kod djece kao i utjecaj navedenog lijeka na preživljenje i duljinu hospitalizacije.
Analizirani su podatci ukupno 20 djece s dijagnozom sepse liječene na Odjelu intenzivnog liječenja na Klinici za pedijatriju KBC-a Rijeka u petogodišnjem razdoblju od 01.01.2019. do 26.03.2024. godine. Svi bolesnici su u terapiji primili imunoglobuline obogaćene IgM. Većina ispitanika je bila muškog spola (65%). Od ukupnog broja bolesnika 15 (75%) su prematurna novorođenčad (gestacijska dob 24-36 tj.). Prosječno trajanje hospitalizacije iznosilo je 55,7 dana. Ukupno je 17 bolesnika primalo imunoglobuline obogaćene IgM kroz pet dana i duljina njihove hospitalizacije je u prosjeku iznosila 61,5 dana. Preostala tri bolesnika su imunoglobuline primala kroz tri dana te je duljina hospitalizacije iznosila 22,6 dana. Ni u jednom slučaju nisu zabilježeni štetni učinci ove terapije.
Obzirom na relativno mali broj ispitanika i činjenicu da je smrt kod preminulih bolesnika nastupila uslijed teških komplikacija prematuriteta, ne može se sa sigurnošću odrediti utjecaj duljine primanja terapije imunoglobulina obogaćenih IgM na duljinu hospitalizacije i mortalitet. Iako su rezultati brojnih studija obećavajući, potrebna su znanstvena istraživanja na većem broju ispitanika u svrhu utvrđivanja učinkovitosti IgM u liječenju sepse i septičkog šoka u djece.As one of the most common diagnostic and therapeutic challenges, sepsis is the most significant cause of morbidity and mortality among newborns and older children. In addition to standard antibiotic treatment, numerous studies have been devoted to studying the clinical effectiveness of IgM-enriched immunoglobulins in treating sepsis.
The aim of this study was to analyze children who were treated with IgM-enriched intravenous immunoglobulin [IgM-IVIG] as an adjunctive pharmacotherapy for sepsis in children, as well as the impact of the mentioned medicine on survival rate and hospitalization duration.
A total of 20 children diagnosed with sepsis were treated at the Intensive Care Unit at the Pediatric Clinic of KBC Rijeka for five years from 01.01.2019 until 26.03.2024. All subjects received IgM-enriched immunoglobulins in therapy. Most patients were male (65%), while fifteen patients (75%) were born prematurely (gestational age 24-36 weeks). The average duration of hospitalization was 55.7 days. A total of 17 patients, among whom four children passed away, received IgM-enriched immunoglobulins for five days, and the average duration of their hospitalization was 61.5 days. The remaining three patients received immunoglobulins for three days, and their duration of hospitalization was 22.6 days. No adverse effects of this therapy were recorded in any case.
Considering the relatively small number of subjects and the fact that the death of deceased patients occurred due to severe complications of prematurity, it is not possible to determine with certainty the influence of the length of receiving IgM-enriched immunoglobulin therapy on the length of hospitalization and mortality. Even though most current research suggests that IgM-enriched immunoglobulin therapy has shown to be a viable option for treating paediatric sepsis and septic shock, more research must be done on a more significant number of subjects so that the effects can be definitively proven
Benign breast lesions mimicking a malignant disease
No full textBenigne lezije dojke najčešće su dijagnoze s kojima se liječnici susreću pri obradi pacijenata s
promjenama na dojkama. Iako benigne naravi, izazivaju zabrinutost te zahtijevaju pažljivu
evaluaciju i točnu dijagnozu kako bi se mogli ispravno odrediti daljnji postupci skrbi. Klinička
slika uključuje širok raspon simptoma, od slučajno otkrivene lezije na rutinskom mamografskom
pregledu do palpabilne mase, iscjetka ili promjene na koži. Zbog toga svaki pacijent zahtijeva
individualni, holistički pristup koji uključuje klinički pregled, radiološku procjenu i
patohistološku evaluaciju uzorka. Benigne lezije heterogena su skupina koja uključuje upalna
stanja, proliferativne bolesti i benigne tumore, a svaka od ovih kategorija sadrži mnoštvo entiteta
koji mogu predstavljati dijagnostički izazov. U ovom radu prikazane su najčešće benigne lezije
te njihove radiološke i patohistološke karakteristike s naglaskom na one komponente koje mogu
odvesti dijagnostičara u krivom smjeru i tako dovesti do pogrešne dijagnoze. Visoka incidencija
benignih stanja dojke koja oponašaju malignu bolest ukazuje da je potrebna pažljiva korelacija
između radioloških i patoloških nalaza.Benign breast lesions are the most common diagnoses doctors encounter when treating patients
with breast changes. Although benign in nature, they cause concern and require careful
evaluation and accurate diagnosis in order to correctly determine further care procedures. The
clinical presentation includes a wide range of symptoms, from an incidentally discovered lesion
on a routine mammographic examination to a palpable mass, discharge, or skin change. For this
reason, each patient requires an individual, holistic approach that includes clinical examination,
radiological assessment and pathohistological evaluation of the lesion. Benign lesions are a
heterogeneous group that includes inflammatory conditions, proliferative diseases and benign
tumors, and each of these categories contains a multitude of entities that can pose a diagnostic
challenge. This paper presents the most common benign lesions and their radiological and
pathohistological characteristics with an emphasis on those components that can lead the
diagnostician in the wrong direction and thus lead to a wrong diagnosis. The high incidence of
benign breast conditions mimicking malignant disease indicates that careful correlation between
radiological and pathological findings is necessary
Brain Abscess
No full textThis thesis presents a comprehensive review of brain abscesses, focusing on their etiology, pathophysiology, clinical presentation, diagnosis, and management. It aims to address the complexities and challenges in diagnosing and treating recurrent brain abscesses through an extensive literature review and a detailed case report. The case report highlights a patient with multiple brain abscesses, detailing the clinical course, diagnostic workup, treatment modalities, and outcomes. The study underscores the intricate pathogenesis of brain abscesses, driven by interactions between microbial virulence factors and the host's immune defenses, necessitating a nuanced approach to both diagnosis and treatment. Clinical features such as headaches, fever, and neurological deficits often complicate early diagnosis, emphasizing the critical role of advanced neuroimaging techniques. Management strategies combining surgical intervention and antimicrobial therapy, tailored to specific pathogens, are explored. The thesis concludes with a synthesis of key findings, identification of knowledge gaps, and recommendations for optimal management and future research