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Background: This report describes data collected by the Croatian Registry of Renal Biopsies (CRRB) for the year 2019. Patients and methods: nine centers (82%) provided data for 255 native kidney biopsies. We assessed the anthropometric data, data on serum creatinine concentration (sCr), 24 h proteinuria, haematuria, serum albumin level, arterial hypertension, histological diagnosis, and complications after renal biopsy. Results: examined group consisted of 58% males, median age 58 y (18-80 y) and 42% women, median age 57 y (20-86 y). Males had a more impaired renal function at the time of renal biopsy, nephrotic syndrome, and hypertension. The most prevalent clinical presentation were urinary abnormalities (34.9%). Among all biopsy cases, primary glomerular diseases were the most often found histology group (41.5%), and IgA nephropathy was the most frequent diagnosis( 47.1%). Among secondary glomerular diseases, pauci-immune glomerulonephritis (PIGN) was most often found (30.9%). The highest proteinuria was observed in minimal change disease and diabetic nephropathy (DN). The highest sCR values were found in membranoproliferative glomerulonephritis (MPGN) and necrotizing vasculitis. Patients with MPGN and DN had the highest blood pressure levels. Conclusion: CRRB provides important data on the epidemiology of biopsy-proven kidney diseases from the whole territory of Croatia, Uvod: izvještaj opisuje podatke Hrvatskog registra biopsija nativnih bubrega za 2019.godinu. Ispitanici i metode: poslani su podaci za 255 biopsija nativnih bubrega. Evidentirana je dob, spol, antropometrijski podaci, serumski kreatinin, 24h proteinurija, eGFR, prisutnost eritrociturije, arterijski tlak, klinička prezentacija, histološka slika i komplikacije biopsije bubrega. Rezultati: ispitivanu grupu činilo je 58% muškaraca, medijan dobi 58 g (18-80 g) i 42% žena, medijan dobi 57 g(20-86 g). Muškarci su se češće prezentirali azotemijom u času biopsije (67,5 %), nefrotskim sindromom (55,7 %) i hipertenzijom (62,5 %). Najčešće klinička prezentacija zbog koje je učinjena biopsija bubrega bio je sindrom eritrociturije i proteinurije (34,9 %). Najčešća skupina bubrežnih bolesti su bile primarne glomerulopatije (41,5 %). Među primarnim glomerularnim bolestima najučestalija je IgA nefropatija (IgAN)(47,1 %), a među sekundarnim glomerulonefritisima pauci imuni glomerulonefritis (PIGN) (30,9 %). Najvišom proteinurijom manifestirali su se od primarnih glomerularnih bolesti bolest minimalnih promjena a od sekundarnih formi dijabetička nefropatija (DN). Najvišim vrijednostima kreatinina u času biopsije manifestirali su se MPGN i PIGN. Hipertenzija je bila najviša kod MPGN i DN. Učestalost ozbiljnih komplikacija zabilježena je u 14 bolesnika (5,8 %). Zaključak: rezultati ukazuju na važne epidemiološke podatke prikupljene iz reprezentativnog broja nefroloških centara s cijelog teritorija Republike Hrvatske.

Introduction Several histologic classifications are used in the evaluation of IgA vasculitis nephritis (IgAVN), however, to date, no studies have determined which one has the strongest association with the severity of IgAVN and, as a consequence, its outcomes. Materials and methods Patients included in the study were diagnosed with IgAV and IgAVN in seven tertiary university medical centers in Croatia, Italy and Israel. The International Study of Kidney Disease in Children (ISKDC), Haas, Oxford, and Software Quality Control (SQC) classifications were used in the analysis and description of renal biopsy. Time from biopsy to outcome evaluation was a statistically significant factor in outcome prediction that was used to define the base model, and was a covariate in all the tested models. Results Sixty-seven patients were included in this study. The SQC classification proved to be the best one in outcome prediction, followed by the Oxford classification. The ISKDC and Haas classifications could not predict renal outcome. The Oxford parameters for mesangial hypercellularity and tubular atrophy, as well as the SQC parameters for cellular crescents showed an independent statistically significant contribution to outcome prediction. High level of twenty-four hour protein excretion was associated with a higher grade in the Oxford, SQC and ISKDC classifications. Endocapillary proliferation was positively associated with the Pediatric Vasculitis Activity Score (PVAS) at diagnosis, while tubular atrophy was negatively associated. Conclusion The SQC, followed by the Oxford classification were found to provide the best classifications of renal biopsy analysis in patients to predict the outcome in patients with IgAVN. Cellular crescents, mesangial hypercellularity and tubular atrophy showed significant contributions, indicating that active and chronic variables should be included in the estimation.

Prostate cancer (PCa) represents a malignancy with high incidence and prevalence rates which are expected to rise further in the following years. In the search for new biomarkers, DNA methylation has been recognized as a key event in PCa development and progression. Therefore, in the present research, DNA methylation of the APC gene in liquid biopsies and tumor tissue of PCa patients, as well as its expression on protein level were investigated. Liquid biopsy samples (blood and ejaculate) and prostate tissue samples were taken from 42 patients with early-stage PCa and 55 with benign prostate hyperplasia (BPH). The degree and pattern of DNA methylation were investigated using pyrosequencing, while protein expression of APC was analyzed using immunohistochemistry. In the blood and seminal plasma of prostate cancer patients compared to BPH patients, there was no significant difference in cfDNA methylation of the APC gene. Moreover, literature data suggesting DNA hypermethylation in tumor tissue compared to surrounding healthy tissue or BPH tissue have not been confirmed. Analysis of APC protein expression showed that APC has higher expression in tumor epithelia than epithelia of surrounding healthy tissue or BPH tissue. In tumor stroma, APC had lower expression compared to the stroma of surrounding healthy tissue or BPH tissue. Based on these results, cfDNA methylation of APC does not have the potential as a biomarker for prostate cancer and its differentiation from BPH. Changes in APC expression on protein level have potential as prostate cancer biomarkers for immunohistochemistry purpose since their expression in tumor epithelium and stroma differs from surrounding healthy and BPH tissue.

This report describes data collected by the Croatian Registry of Renal Biopsies (CRRB) for the year 2019. Patients and methods: nine centers (82%) provided data for 255 native kidney biopsies. We assessed the anthropometric data, data on serum creatinine concentration (sCr), 24 h proteinuria, haematuria, serum albumin level, arterial hypertension, histological diagnosis, and complications after renal biopsy. Results: examined group consisted of 58% males, median age 58 y (18-80 y) and 42% women, median age 57 y (20- 86 y). Males had a more impaired renal function at the time of renal biopsy, nephrotic syndrome, and hypertension. The most prevalent clinical presenta tion were urinary abnormalities (34.9%). Among all biopsy cases, primary glomerular diseases were the most often found histology group (41.5%), and IgA nephropathy was the most frequent diagno sis(47.1%). Among secondary glomerular diseases, pauci-immune glomerulonephritis (PIGN) was most often found (30.9%). The highest proteinuria was observed in minimal change disease and dia betic nephropathy (DN). The highest sCR values were found in membranoproliferative glomerulone phritis (MPGN) and necrotizing vasculitis. Patients with MPGN and DN had the highest blood pressure levels. Conclusion: CRRB provides important data on the epidemiology of biopsy-proven kidney diseases from the whole territory of Croatia.

Background: Optimal prognostic predictors in lupus nephritis (LN) are still not clearly defined. Studies have recently shown that albumin-to- globulin ratio (A/G) is not only a good predictor of outcomes in malignancy, infection and renal disease, but is also a potential marker of increased immunoglobulin synthesis and LN activity and might be useful as a predictor of the development of LN in SLE patients. Studies on the role of A/G in predicting outcomes in LN are, however, lacking. Objectives: To assess a potential prognostic value of A/G at renal biopsy in predicting outcomes in LN. Methods: In this retrospective study we analyzed the demographic, histologic, laboratory and clinical characteristics of patients with biopsy- proven LN diagnosed between 2011 and 2020. All patients met the 1997 revised American College of Rheumatology classification criteria for SLE. Complete remission was defined as proteinuria 0.05 ; Figure 1 ) and was not a significant predictor of remission in a multivariate regression model (OR 5.9, 95% CI 0.6, 63.2). Conclusion: While being a potential marker for transition of SLE to LN, A/G was not showed to be a predictor of renal remission in LN.

Introduction: Macrophages frequently infiltrate injured glomerular and tubulointerstitial tissue, and it is possible that the degree and subtype of macrophage infiltration (M1 macrophages, which show proinflammatory features, and M2 macrophages, with their immunosuppressive features) varies depending on the type and severity of renal injury. Although renal involvement in patients with Henoch-Schönlein's purpura (HSP) is the main cause of morbidity and mortality and a significant prognostic determinant for the disease outcome, a reliable prognostic factor for severe forms of HSP nephritis (HSPN) is yet to be determined. Objectives: The aim of this research was to determine macrophage subclasses in renal biopsy specimens of HSPN patients and to analyze their quantity in regard with patients' clinical parameters and histologic features. Methods: We performed an immunohistochemical study on renal tissue samples of patients with HSPN, diagnosed by EULAR/PRINTO/PRES criteria and followed for at least 6 months. Patient clinical and laboratory data was retrieved from hospitals' medical records. Renal biopsy samples were marked with antibodies for CD68, iNOS and arginase. The number of immunoreactive cells was counted in each glomerulus by two independent experts. Results: Laboratory and histologic data for 25 patients with HSPN was evaluated in regard with macrophage infiltration of the renal tissue. The median glomerular M1 and M2 counts (q1, q3) were 2.3 (0.9, 12.2) and 7.6 (4.4, 13.9), respectively. M1 macrophages were found statistically significantly less frequent in the glomeruli in comparison with M2 macrophages (p < 0.001, b = -0, 289 ± 0.053). Collected laboratory data included inflammatory markers and markers of kidney function. There was no significant correlation between M1 and M2 macrophage count and laboratory parameters. Four pathohistological classifications were used: ISKDC, Haas classification, Oxford classification, and SQC classification. Classification stages/total classification scores and all histological variables were evaluated for possible correlation with macrophage count. Statistically significant negative correlation was found between segmental glomerulosclerosis (Oxford classification) and M2 macrophages (p = 0, 001, b = -1, 050 ± 0, 275). An indication of negative correlations was also noted between M2 macrophages and segmental sclerosis, and M2 macrophages and adhesions (SQC classification). Conclusion: Glomeruli in HSPN showed predominant M2 polarization of macrophages. M2 macrophage infiltration of glomeruli was highlighted as a possible negative predictor for segmental glomerulosclerosis. Grant/research support: Croatian Science Foundation project PURPURAPREDICTORS IP-2019-04- 8822 and University of Rijeka, Croatia grant No. Uni-ri-biomed-18-110.

Introduction: primary membranous nephropathy (pMN) is glomerulopathy caused in the majority of cases by autoantibodies to Phospholipase-A2 receptors (PLA2R-AB). This study aimed to evaluate the clinical course and outcomes of the patients with pMN regarding PLA2R-AB status. Patients and methods: 32 patients (21 males, 11 females) with renal biopsy-proven pMN were included in the study. PLA2R-AB (ELI SA method) and outcomes (defined according to KDIGO) were evaluated after 21 and 64 months of follow-up in 28 patients. Results: 19 patients had positive PLA2R-AB (>20 RU /ml) (59.3%), with median titer of 97 (21-1418 RU /ml). The rate of remission in low PLA2R-AB titer group (< 200 RU /ml) after 21 months was significantly higher than in high PLA2R-AB group (> 200 RU /ml) (90% vs. 50%, p=0.045), and after 64 months the difference was not significant (80% vs. 50%, p=0.210). The relapse rate after 64 months was higher in the high PLA2R-AB group (87% vs. 63%). Multivariant linear regression found serum creatinine (ß=0.682, p, Uvod: primarna membranska nefropatija (pMN) je glomerulopatija, koja je u većini slučajeva uzrokovana autoprotutijelima na receptor za fosfolipazu A2 (PLA2R-PT). Cilj ovog istraživanja bio je analizirati povezanost PLA2R-PT s kliničkim tijekom i ishodima bolesti. Ispitanici i metode: 32 bolesnika (21 muškaraca, 11 žena), s biopsijom bubrega dijagnosticiranim pMN, bilo je uključeno u istraživanje. PLA2R-PT (ELI SA metoda) i ishodi (definirani u skladu s KDIGO) određeni su nakon 21 i 64 mjeseca praćenja u 28 bolesnika. Rezultati: 19 bolesnika imalo je pozitivna PLA2R-PT (>20 RU /ml) (59.3%), s medijanom titra 97 (21-1418 RU /ml). Stopa remisije u skupini s niskim titrom PLA2R-PT (< 200 RU /ml) nakon 21 mjeseca bila je značajno viša u odnosu na skupinu s visokim titrom PLA2R-PT (> 200 RU /ml) (90% vs. 50%, p=0.045), a nakon 64 mjeseca razlika nije bila značajna (80% vs 50%, p=0.210). Stopa relapsa nakon 64 mjeseca bila je viša u skupini s visokim titrom PLA2R-PT (87% vs. 63%). Multivarijatnom linearnom regresijom su kao značajni neovisni prediktori za bubrežnu funkciju na kraju praćenja nađeni serumski kreatinin (ß=0.682, p

Lupus nephritis (LN) is one of the most severe features of systemic lupus erythematosus (SLE). Data on LN is scarce in the Croatian population. We analysed the characteristics of LN patients diagnosed at our tertiary referral centre. In this retrospective study, we analysed the following features of patients with biopsy-proven LN diagnosed between 2011 and 2020: demographics, renal laboratory parameters, renal histopathology, and treatment. A total of 38 patients were included (30 females; mean age 39±15 years). The most common indication for kidney biopsy was proteinuria (89%). The proportion of LN classes was: class I (2.6%), II (5.3%), III (18.4%), IV (42.1%), V (13.2%), III+V (10.5%), IV+V (5.3%). The median time from SLE diagnosis to histologic confirmation of LN was 1.0 year. All patients were treated with methylprednisolone (MP), 68% received MP pulses. Induction treatment included intravenous (IV) cyclophosphamide (CYC) (71%) (15 patients treated per Euro-Lupus and 9 per the National Institutes of Health regimen), oral CYC (3%), or mycophenolate mofetil (11%). 79% of patients received antimalarials. While there is heterogeneity between different populations, our patient profile was similar to that from other European studies. Further follow-up of this group is necessary to assess outcomes in our population., Lupusni nefritis (LN) je česta i vrlo ozbiljna manifestacija sustavnog eritemskog lupusa (SLE). Još uvijek nema dovoljno podataka o karakteristikama bolesnika s LN u Hrvatskoj. Analizirali smo karakteristike bolesnika s LN koji su liječeni u referentnom centru naše tercijarne ustanove. U ovu retrospektivnu studiju uključili smo bolesnike s biopsijom potvrđenim LN u periodu od 2011. do 2020. godine, analizirali smo demografske podatke, parametre bubrežne funkcije, patohistološki nalaz bioptata bubrega i liječenje. U studiju je uključeno 38 bolesnika (30 žena, prosječna dob 39±15godina). Najčešća indikacija za biopsiju bubrega bila je proteinurija (89%). Raspodjela klasa LN bila je sljedeća: klasa I(2,6 %), II(5,3 %), III(18,4 %), IV(42,1 %), V(13,2 %), III+V(10,5 %), IV+V(5,3 %). Prosječno vrijeme od dijagnoze SLE do histološke potvrde LN bilo je 1,0 godina. Svi bolesnici su liječeni kortikosteroidima, 68 % liječeno je bolusima metilprednizolona. Indukcijska terapija uključivala je parenteralnu primjenu ciklofosfamida (CYC) (71 %) (15 bolesnika liječeno je prema Euro-lupus protokolu, 9 bolesnika prema protokolu Nacionalnog instituta za zdravlje (NIH)), peroralni CYC (3 %) ili mikofenolat mofetil (11 %). Antimalarike je primilo 79 % bolesnika. Unatoč heterogenosti između različitih populacija s LN, profil bolesnika uključen u ovu studiju sličan je ostalim europskim studijama. Daljnje praćenje potrebno je da bi se istražili ishodi u ovoj populaciji.

Indroduction: IgA vasculitis (IgAV) is the most common childhood-vasculitis in which more than 50% of children develop gastrointestinal (GI) symptoms. In 10-20% of patients serious complications such as intussusception, bowel perforation, and massive bleeding may occur. The most important complication is the development of nephritis with progression to chronic renal failure in about 3% of children. The aim of the research was to analyze clinical and biochemical parameters in patients with IgAV and GI manifestations. Methods: This retrospective study included children with IgAV reviewed in five Croatian University Centers for pediatric rheumatology in the period 2009 to 2019. Results: Out of 611 children with IgAV, 320 were males and 291 were females. The overall GI symptoms prevalence was 45.9% and the median (range) age at diagnosis was 6.42 (4.5- 8.83) years. Among patients with GI symptoms there were 1.44 times more males (N=166) than females (N=115), which was statistically significant (p=0.003). Patients with GI symptoms had less infections before the appearance of purpura (59.8% vs. 70.9%, p=0.005) and were found to be significantly more likely to have rash distributed on the trunk (61.9% vs. 48.5%, p=0.001), and upper extremities (35.2% vs. 24.7%, p=0.006), as well as generalized rash (38.8% vs. 28.3%, p=0.008). These patients also had significantly higher values of C-reactive protein, leukocyte count, erythrocytes and platelets, hemoglobin, hematocrit and D-dimer concentrations and lower levels of IgG and IgM. In our cohort 42 out of 281 children (14.9%) had the most severe GI manifestations (intussusception and/or massive GI bleeding) with significantly higher values of 24-hour urine protein levels and D-dimer concentrations and lower total serum protein, albumin, IgG, IgM and C3 levels in comparison with children whose GI manifestations were not severe. Predictors of severe GI involvement were: relapse of the disease, generalized rash, rash extended on upper extremities, rash extended to the face, recurrent rash and renal involvement, as well as lower values of prothrombin time, fibrinogen and IgM among the laboratory parameters. Patients with GI symptoms were 1.68 times more likely to develop nephritis, and this probability was 2.58 times higher if GI symptoms occurred before other symptoms. Other predictors of nephritis were: severe and moderate GI manifestations, recurrent rash, one or more relapses of IgAV, and older age. Conclusion: Older children with IgAV and severe GI manifestations in whom IgAV begun with GI symptoms had a higher risk of acute and chronic complications of the disease. SUPPORT: Croatian Science Foundation project IP- 2019-04-8822

Uvod. Makrofagi, kategorizirani kao M1 (kalprotektin+ podvrsta) ili M2 (CD163+ podvrsta) infiltriraju glomerule i tubulointersticij bubrega u bolesnika s Henoch-Schönlein-ovom purpurom (HSP- om). Broj tubulointersticijskih CD163+ makrofaga moćno predskazuje kronično bubrežno zatajivanje. Arginaza-1 jest biljeg svih M2 makrofaga, a inducibilna sintaza dušikovog oksida (iNOS) je biljeg svih klasično aktiviranih makrofaga M1. iNOS predstavlja aktivnost upalne bolesti, ukoliko je izražena na epitelnim stanicama crijeva. Međutim, uključenost iNOS u razvoju HSP-e je za sada neizvjesna. Cilj ovog rada je bio utvrditi raspodjelu CD68+, iNOS+ i arginaza-1+ stanica u bioptatu bubrega bolesnika s HSP-om te tkivni međuodnos CD68+ stanica i izvršnih imunoloških stanica CD3+ iCD56+ fenotipa. Ispitanici i metode. CD68, iNOS i arginaza-1 su obilježavani metodom imunohistologije (reakcija imunoperoksidaze uz vizualizaciju diaminobenzidinom), dok je dvostruko obilježavanje iNOS, arginaza-1, CD3 iliCD56 s CD68 biljegom učinjeno metodom dvostruke imunofluorescencije (uz vizualizacju primarnih mišjih ili zečjih protutijela sekundarnim protutijelima obilježenim fluorescentnim bojama Alexa fluor 488 i Alexa fluor 594) u biopsijama bubrega 22 bolesnika s nefritisom u sklopu HSP. Rezultati. Broj CD68+ stanica je podjednak u glomerulima [4, 6 (2, 6 ; 13, 7)] i tubulointersticiju [3, 3 (2 ; 6, 2)], [median (25. i 75. percentila)]. Također je podjednak broj arginaza-1+ i iNOS+ stanica u glomerulima, intersticiju i epitelnim stanicama tubula. U glomerulima i tubulima obilježile su se dvostruko pozitivne CD68+/iNOS+ stanice, međutim samo rijetke CD68+/arginaza-1+ stanice. MorfološkiCD68+ i iNOS+ stanice prepoznaju se kao razgranati makrofagi, ali i kao kuboidne tubularne epitelne stanice. Nakupine CD3+ limfocita utiskivale su se u intersticij, a znatno manje u glomerule, te nalazile u blizini makrofaga i tubularnih epitelnih stanica. CD56+ limfocitisu se rijetko obilježavali, uglavnom u glomerulima. Zaključak. Pored CD68+ makrofaga, tubularne epitelne stanice izražavaju CD68 i predstavljaju važan izvor iNOS- a, koje ograđuju brojniCD3+ limfociti. Funkcijski međuodnos iNOS+CD68+ stanica i limfocita tek treba istražiti, kao i njihovu povezanost s aktivnošću nefritisa. Financiranje istraživanja: projekt HRZZ br. IP- 2019-04-8822, projekt Sveučilišta u Rijeci br. Uni-ri-biomed- -18-110.

Introduction: primary membranous nephropathy (pMN) is glomerulopathy caused in the majority of cases by autoantibodies to Phospholipase-A2 receptors (PLA2R-AB). This study aimed to evaluate the clinical course and outcomes of the patients with pMN regarding PLA2R-AB status. Patients and methods: 32 patients (21 males, 11 females) with renal biopsy-proven pMN were included in the study. PLA2R-AB (ELISA method) and outcomes (defined according to KDIGO) were evaluated after 21 and 64 months of follow-up in 28 patients. Results: 19 patients had positive PLA2R-AB (>20 RU/ml) (59.3%), with median titer of 97 (21-1418 RU/ml). The rate of remission in low PLA2R-AB titer group (< 200 RU/ml) after 21 months was significantly higher than in high PLA2R-AB group (> 200 RU/ml) (90% vs. 50%, p=0.045), and after 64 months the difference was not significant (80% vs. 50%, p=0.210). The relapse rate after 64 months was higher in the high PLA2R- AB group (87% vs. 63%). Multivariant linear regression found serum creatinine (ß=0.682, p

IgA vasculitis nephritis (IgAVN) is almost the only cause of morbidity and mortality among children suffering from this most common childhood-vasculitis. Several histological classifications are used in the analysis of renal biopsy findings in IgAVN, but it remains unknown which one is the best predictor of severity and disease outcome. The aim was to compare the four most commonly used histologic classifications for IgAVN and to establish which variables of each histological classification have the strongest association with unfavorable outcome. The cross- sectional study included 74 patients with IgAVN (diagnosed by EULAR/PRES/PRINTO criteria) and available renal biopsy specimens for analysis using the four histological classifications for IgAVN (the International Study of Kidney Disease in Children (ISKDC) classification, the Oxford classification, the Haas histologic classification of IgA nephropathy and the modified semi- quantitative classification (SQC), developed by Koskela et al.). The clinical outcome was defined through four categories, graded according to the modified classification of Counahan (physical examination, hematuria, proteinuria, urine albumin-tocreatinine ratio, hypertension and eGFR). The linear relationships between outcome and histological classifications were analysed using ordinal regressions using the first-order of polynomial orthogonal contrasts. The SQC classification proved to be the best, reducing the deviation (of the model-predicted outcome value from the observed value) by 9.5% (c21=13, 89, p

Background: A number of blood count parameters are associated with inflammatory and autoimmune diseases. There is discordant evidence whether neutrophil-to-lymphocyte ratio (NLR), platelet-to- lymphocyte ratio (PLR) and mean platelet volume (MPV) might reflect inflammatory response and have prognostic value in SLE patients. However, the studies examining the potential role of these markers in LN are missing. Objectives: To examine NLR, PLR and MPV at the time of biopsy in patients with LN and evaluate their association with prognosis. Methods: In this retrospective study we analyzed the demographic, histologic, laboratory and clinical characteristics of patients with biopsy- proven LN diagnosed between 2011 and 2020. All patients met the 1997 revised American College of Rheumatology classification criteria for SLE. Complete remission was defined as proteinuria 0.05). Eighteen patients achieved complete remission (CR), 16 partial remission and 21 did not achieve remission. None progressed to ESRD and two patients died, both from sepsis. There no differences in NLR, PLR and MPV at the time of biopsy between group which achieved CR/PR vs. no remission (all p>0.05 ; Figure 1 ). We constructed a thorough multivariate regression model which showed that neither NLR, PLR or MPV are predictors of renal remission in LN. Conclusion: NLR, PLR and MPV are not useful prognostic markers in predicting renal remission in LN.

The prevalence of generalized skin symptoms, as well as the most severe forms in childhood IgA vasculitis is much less than the classical findings. However, the more severe the skin symptoms are, the more severe the course of the disease is, and aggressive treatment will be needed.

Uvod: IgA vaskulitis (IgAV) najčešći je vaskulitis u djece. Iako se uglavnom radi o samoograničavajućoj bolesti, u više od 50% djece mogu se razviti gastrointestinalni (GI) simptomi, a u oko 10 do 20% djece moguća je pojava ozbiljnih komplikacija kao što su intususcepcija, perforacija crijeva ili opsežno krvarenje iz probavnog sustava. Ispitanici i metode: U ovo retrospektivno istraživanje uključili smo djecu s IgAV-om koja su se liječila u 5 tercijarnih ustanova za pedijatrijsku reumatologiju u Hrvatskoj u razdoblju od 2009. do 2019. godine. Razlike među kategorijskim varijablama ispitane su χ2 i Fisherovim egzaktnim testom, a među numeričkim Mann-Whitneyevim U testom. Rezultati: Od 611 djece s IgAV-om u njih 281 (45, 9%) bio je zahvaćen GI sustav. Među djecom s GI simptomima bilo je 1, 44 puta više dječaka (p = 0, 003), više ih je dolazilo iz mediteranske Hrvatske (38% u odnosu na 27%, p = 0, 007), imala su manje infekcija prije pojave purpure (59, 8% u odnosu na 70, 9%, p = 0, 005) i manje respiratornih infekcija (35, 6% u odnosu na 45, 2%, p < 0.001). U djece koja su imala GI simptome postojala je 1, 68 puta veća šansa za razvoj nefritisa, a ako je IgAV započeo s GI simptomima, tada je ta šansa bila čak 3, 55 puta veća. Nije bilo razlike u zahvaćenosti zglobova i središnjeg živčanog sustava. U djece s GI simptomima osip je bio značajno češće proširen po trupu (61, 9% u odnosu na 48, 5%, p = 0, 001) i gornjim ekstremitetima (35, 2% u odnosu na 24, 7%, p = 0, 006), a češće se pojavljivao generalizirani osip (38, 8% vs. 28, 3%, p = 0, 008). Ova je skupina djece imala više razine C-reaktivnog proteina, veći broj leukocita, eritrocita i trombocita, više koncentracije hemoglobina i D-dimera te niže koncentracije IgG i IgM. Najteže GI manifestacije imalo je 42 od 281 djece (14, 9%) i ona su imala značajno veću 24- satnu proteinuriju i povišene koncentracije D- dimera te niže koncentracije serumskih bjelančevina, albumina, IgG, IgM i komponente C3 komplementa u odnosu na djecu s lakšim GI manifestacijama. Zaključak: Pronašli smo skupinu djece s IgAV-om i GI simptomima koja su se razlikovala u svojim demografskim, kliničkim i biokemijskim obilježjima od djece bez GI simptoma. Ova skupina djece imala je statistički značajno veću šansu za razvoj nefritisa, a time i veći rizik za pojavu akutnih i kroničnih komplikacija IgAV-a. Potpora: Projekt Hrvatske zaklade za znanost, IP- 2019-04-8822

The pilot study showed that the SQC classification, developed by Koskela et al., has the strongest association with the severity and outcome of HSPN, followed by the Oxford classification, while other classifications are less related to the outcome of the disease.

Uvod: Henoch-Schönleinov purpurni nefritis (HSPN) najvažniji je uzrok pobola i smrtnosti u ovom najčešćem dječjem vaskulitisu. Postoji nekoliko histoloških klasifikacija HSPN-a, ali nije poznato koja je najbolje povezana s ishodom bolesti. Cilj je rada usporediti četiri najčešće histološke klasifikacije za HSPN, odrediti koja najbolje predviđa ishod te utvrditi povezanost pojedinih histoloških varijabli s ishodom bolesti. Ispitanici i metode: Presječna studija uključila je 72 bolesnika s HSPN-om. Biopsije bubrega analizirane su prema četiri dostupne histološke klasifikacije: ISKDC-ova (engl. International Study of Kidney Disease in Children), Oxfordska, Haasova te modificirana semikvantitativna klasifikacija Koskele i sur. (engl. Modified Semiquantitative Classification – SQC). Klinički ishod definiran je kroz četiri kategorije prema modificiranoj Counahanovoj klasifikaciji. Linearni odnosi između ishoda i histološke klasifikacije analizirani su metodom ordinalne regresije koristeći prvi red polinomnih ortogonalnih kontrasta. Rezultati: Najboljom se pokazala SQC- ova klasifikacija koja je smanjila devijaciju (modelom predviđene vrijednosti ishoda u odnosu na stvarnu vrijednost ishoda) za 9, 5% (Χ21 = 13, 89, p < 0, 001), nakon nje Oxfordska sa smanjenjem devijacije za 8, 0% (Χ21 = 11, 76, p = 0, 001), zatim ISKDC-ova sa smanjenjem devijacije za 3, 3% (Χ21 = 4, 89, p = 0, 027), a najlošijom se pokazala Haasova klasifikacija sa smanjenjem devijacije za 2, 1% (Χ21 = 3, 06, p = 0, 080). Uočeno je da porast vrijednosti intersticijske fibroze (t66 = 3, 23, p = 0, 002), tubularne atrofije (t66 = 2, 94, p = 0, 005) i tubularne dilatacije (t66 = 2, 40, p = 0, 019) u SQC-ovoj klasifikaciji te endokapilarne hipercelularnosti (t66 = 3, 14, p = 0, 003) i polumjeseca (t66 = 2, 07, p = 0, 043) u Oxfordskoj klasifikaciji pogoršava ishod bolesti. Zaključak: Pilot studija pokazala je da SQC-ova klasifikacija ima najbolju povezanost s lošim ishodom HSPN-a. Iako se smatralo da su polumjeseci u bioptatima bubrega najvažniji pokazatelj ishoda, ovo istraživanje sugerira da bi tubulointersticijske promjene mogle biti važnije u predviđanju lošeg ishoda. Tubulointersticijske promjene u HSPN-u trebaju se dalje istraživati kako bi se ustanovilo imaju li bolju prediktivnu vrijednost u ishodu bolesti i prema tome ih ugraditi u postojeće ili nove klasifikacije. Potpora: Projekt Hrvatske zaklade za znanost, IP- 2019-04-8822

We detected a group of patients with HSP and GI symptoms that differed in their demographic, clinical, and biochemical characteristics from patients without GI symptoms. This group of patients was found to be significantly more likely to develop renal disease and thus cumulatively have a higher risk of acute and chronic complications of HSP.

Bitan dio liječenja karcinoma u području glave i vrata je radioterapija. Sluznica farinksa i larinksa je građena od stanica brze mitotičke aktivnosti, složene je mikroflore i izložena je svakodnevnoj traumatizaciji vanjskim čimbenicima, pa je izrazito osjetljiva na utjecaj ionizacijskog zračenja prilikom provođenja radioterapije. Intezitet oštećenja sluznice ovisi o dozi zračenja, bolesnikovoj dobii komorbiditetima, a predisponirajući je čimbenikza razvoj oportunističke infekcije i karcinoma.Prikazujemo slučaj 54-godišnjeg muškarca, koji se javio u hitnu ambulantu zbog disfagije i odinofagije unazad mjesec dana. U anamnestičkim podacima radioterapija vrata prije 20 godina nakon resekcije planocelularnog karcinoma donje usne. Pušač, konzument alkohola. Kliničkim pregledom ulkusna promjena obje valekule prekrivena fibrinom, te se zbog sumnje na tumorski proces učini obrada. Opetovanim biopsijama nije se dobila potvrda malignog tumora, već nalaz displazije imoguće gljivične infekcije. Obzirom na nekrotično tkivo i sijelo promjene odlučilo se učiniti supraglotičnu laringektomiju. Patohistološka dijagnoza kod bolesnika s pojavom ulkusa sluznice u ozračenoj regiji ključan je korak za pravovremeno i ispravno liječenje. Diferencijalno-dijagnostički, osim primarnog tumora ili recidiva, u malom postotku može se raditi o kroničnom ulkusu uzrokovanom gljivičnom ili bakterijskom infekcijom, granulomatoznom upalom, Behcetevoj bolesti te gastroezofagealnom refluksu. Ulkus sluznice regije koja je prethodno zračena zahtijeva radikalno odstranjenje zbog patohistološke dijagnostike i planiranja daljnjeg liječenja.

Adenokarcinom prostate najčešća je zloćudna neoplazma u muškaraca u Republici Hrvatskoj. Klinički je često asimptomatski, a najčešće se otkriva na osnovi povišenih vrijednosti PSA u serumu. Odluka o liječenju donosi se na temelju TNM-klasifikacije, gradusne skupine i vrijednosti PSA. Klinički lokalizirana bolest vrlo se uspješno liječi radikalnom prostatektomijom ili radikalnom radioterapijom s hormonskom terapijom ili bez nje. Klinički lokalno uznapredovala bolest najčešće se liječi združenom primjenom radikalne radioterapije i hormonske terapije. Metastatska bolest godinama se može kontrolirati androgenom deprivacijom, a nakon razvoja kastracijski rezistentne bolesti opravdani su kemoterapija ili dodatni oblici hormonske terapije. U radu su prikazane kliničke upute radi ujednačenja postupaka i kriterija postavljanja dijagnoze, liječenja i praćenja bolesnika s rakom prostate u Republici Hrvatskoj., Prostate adenocarcinoma is the most common solid neoplasm in male population in Croatia. It is often asymptomatic. The finding of PSA rise is the most common reason for diagnostic workout. Treatment plan is based on TNM classification, grade group and PSA. Clinically localized disease is successfully treated by radical prostatectomy or radiotherapy with or without hormonal therapy. Locally advanced disease is treated with radiotherapy and hormonal therapy. Metastatic disease can be controlled for many years by androgen deprivation. For castration resistant metastatic disease appropriate treatment is chemotherapy or secondary hormonal therapy. The following paper presents the clinical guidelines to standardize procedures for the diagnosis, treatment and follow-up of patients with prostate cancer in the Republic of Croatia.

This project includes two interconnected goals. The first is to establish a new Scientific Group for Research on Epigenetic Biomarkers, epiMark. Scientists gathered through epiMark are already active in studying male reproductive health and disease, therefore will contribute to the next general goal: studying po tential epigenetic biomarkers (EB) in liquid biopsies of patients diagnosed with prostate cancer (PCa). PCa is second in inci dence and third cause of cancer deaths in Croatia, with incidence rates steadily rising. Contrarily, Croatia records a fall in PCa research. With PSA being quite sensitive biomarker, but not spe cific for PCa, there is a need for developing new diagnostic tools. Our aim is to investigate microRNA and DNA methylation which may serve as potential EB for PCa risk and disease pro gression, and tools for differentiating PCa and benign prostate hyperplasia (BHP). According to recent findings, we chose a set of miRNAs and gene promoter regions believed to be associated with PC development and progression. The study will be con ducted on volunteers diagnosed with PCa and BHP within rou tine at Urology departments of UHC Zagreb and UHC Sestre milosrdnice. In seminal fluid and blood, profiles of genes DNA methylation within cfDNA will be identified by pyrosequencing, while expression of miRNA by qPCR and ddPCR. Epigenetic analysis of gene expression will be performed on patient cancer tissues as well. By comprehensible statistical analysis, we expect to identify potential EB of PCa in liquid biopsies Acknowledgments: This study was supported by Instalation reserch project UIP-2017-05-8138 „Epigenetic biomarkers in prostate cancer“ financed by Croatian Science Foundation and cofinanced by School of Medicine University of Zagreb.

Prostate cancer (PCa) is second in incidence and third cause of cancer deaths in Croatia, with incidence rates steadily rising. Contradictory, Croatia records a fall in PCa research. Project Epigenetic biomarkers of prostate cancer (epiPro) includes two interconnected goals. The first is to establish a new Scientific Group for Research on Epigenetic Biomarkers, epiMark. Scientists gathered through epiMark are already active in studying male reproductive health and disease, therefore will contribute to the next general goal: studying potential epigenetic biomarkers (EB) in liquid biopsies of patients diagnosed with PCa. Prostate specific antigen (PSA) is sensitive but not specific biomarker for PCa so new diagnostic and prognostic tools are needed. Our aim is to investigate microRNA and DNA methylation which may serve as potential EB for PCa risk and disease progression, and tools for differentiating PCa and benign prostate hyperplasia (BPH). According to recent findings, we chose a set of miRNAs and gene promoter regions believed to be associated with PC development and progression. This ongoing study is conducted on 100 volunteers diagnosed with PCa and BPH at Urology departments of UHC Zagreb and UHC Sestre milosrdnice. In seminal fluid and blood, profiles of genes DNA methylation within cfDNA will be identified by pyrosequencing, while expression of miRNA by qPCR and ddPCR. Epigenetic analysis of gene expression will be performed on patient cancer tissues as well.

Rak testisa najčešći je solidni tumor u muškaraca u dobi od 15. do 34. godine. Incidencija raka testisa u svijetu udvostručena je u posljednjih 40 godina. Tumori zametnih stanica čine 95% svih tumora testisa, a podijeljeni su u dva osnovna histološka tipa: seminomi i neseminomi. Osobito značenje daje im velik postotak izlječivosti i u diseminiranoj fazi bolesti. Tom je uspjehu najviše pridonijela kemoterapija, ali kirurgija je i dalje neizostavan dio uspješnog liječenja. U znatnog dijela bolesnika danas se nastoji odrediti terapijski minimum kojim se izbjegava niz nuspojava, a dovodi do jednakog uspjeha kao i donedavno agresivniji terapijski pristup. U tekstu koji slijedi iznesene su kliničke upute radi standardizacije dijagnostike, liječenja i praćenja bolesnika s tumorima zametnih stanica testisa u Republici Hrvatskoj.