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Epilepsy is one of the most prevalent chronic neurological diseases, affecting about 70 million people worldwide. Patients with epilepsy often encounter cognitive dysfunction, which is influenced by different factors including age at the onset of epilepsy, etiology of epilepsy, type of seizures, seizure frequency and duration, psychiatric comorbidity, and antiepileptic drug (AED) therapy. Event-related potentials are useful, noninvasive, objective clinical and research instrument for evaluation of cognitive functions in patients. The aim of this study was to investigate and determine the effect of AED monotherapy and polytherapy on cognitive changes in patients with epilepsy, detected with P300 event-related potentials and compared with age- and gender-matched healthy individuals. The study was conducted in 82 patients with generalized and focal epilepsy and 82 healthy individuals aged 18-65 years. Cognitive evoked P300 potentials were recorded in all study subjects using auditory 'oddball' paradigm. The results showed the patients taking AED polytherapy to have a significantly longer P300 latency and significantly lower N200-P300 amplitude. These results indicate that AED polytherapy might worsen cognitive impairment in patients with epilepsy.

The main obstacle in treatment of infections caused by carbapenem-resistant Enterobacterales (CRE) are limited treatment options. The novel antimicrobial agents other than β-lactams with activity not being dependent on β-lactamase class are especially important. Eravacycline (ERV) is the first fully synthetic fluorocycline indicated for the treatment of complicated intra-abdominal infections in adults. Eighty CRE isolates at the University Hospital Centre Zagreb, Croatia were examined for susceptibility to ERV by disc diffusion method and minimal inhibitory concentration (MIC). Total of 54 (54/80 ; 67.5%) isolates were susceptible to ERV with MIC50 of ≤0.5 μg/mL and MIC90 of 4 μg/mL. Susceptibility of OXA-48 positive isolates was not significantly higher in comparison with NDM positive (P = 0.539) and VIM positive (P = 0.7805) isolates. ERV is possible alternative to novel β-lactamase inhibitor combinations for treatment of CRE infections with antimicrobial susceptibility testing of CRE isolate to ERV in particular patient as condicio sine qua non before administration.

BACKGROUND AND AIMS Graphical Abstract In kidney transplantation, day-zero biopsies are used to assess organ quality and discriminate lesions inherited from the donor or acquired after transplantation. However, many centres worldwide do not perform those biopsies which remain invasive, costly and may delay the transplant procedure. We aimed to develop and validate a noninvasive virtual biopsy system. METHOD A total of 17 centres were included from Europe, North America and Australia from 2000 to 2019. Candidate predictors were assessed following a prespecified protocol. Outcome measures were the day-zero biopsy lesions (Banff classification) including CV, AH, IFTA scores and % of sclerotic glomeruli. Six machine learning models were developed and their performances were assessed. RESULTS A total of 12 992 day-zero biopsies were included. Eleven parameters were used to build the classifiers, including donor age, kidney function, hypertension, BMI, proteinuria, diabetes, sex, donor type, cause of death and Hep-C status. The ensemble models (random forests, neural networks, gradient boosting, extreme gradient boosting tree, linear discriminant analysis, and naive Bayes) showed multi-AUC of 0.738, 0.817 and 0.788 for prediction of CV, AH and IFTA scores, and a good performance for predicting glomerulosclerosis (mean absolute error, MAE = 4.766). We confirmed the robustness and generalizability in multiple clinical scenarios and subpopulations and built an online interface for clinicians: https://transplant-pred/Virtual_Biopsy. CONCLUSION We developed and validated the first virtual biopsy system that enables the prediction of day-zero biopsy, based on routinely collected parameters. This can assist clinicians in assessing allograft quality, discrimination of donor derived versus acquired lesions after transplantation and prevent overdiagnosis of calcineurin inhibitor (CNI) toxicity.

Aim: Data on the use of novel anticoagulant drugs (NOACc) in renal transplant recipients is scarce. The aim of our study was to investigate the safety and efficacy of NOACs in renal transplant recipients. Materials and Methods: In a single-centre retrospective cohort study we assessed adverse reactions, thromboembolic events, and interactions of calcineurin inhibitors in patients treated with NOACs. Results: Twenty-three renal transplant recipients were treated with NOACs (70% male), mean age of 65.8 ± 1.8 years. Fourteen (61%) patients were treated with rivaroxaban, apixaban was given to 8 (35%) of our patients, and dabigatran to one patient (4%). The main indications for NOAC therapy was atrial fibrillation in 61% and deep venous thrombosis in 23% of patients. Bleeding occurred in 2 patients (1 treated with rivaroxaban and 1 with dabigatran). None of our patients developed thrombosis while treated with NOAC. During the median follow-up of 24 months graft function, as well as hematological parameters, remained stable in patients that were treated with rivaroxaban and apixaban, while dabigatran was ceased after a month of therapy due to a bleeding event. Conclusion: Our results show that both rivaroxaban and apixaban are safe and efficient oral anticoagulant drugs in renal transplant patients. Additional studies are needed to prove these results.

Background: Data on the cardiorenal syndrome (CRS) in renal transplant recipients (RTR) are scarce. We investigated the prevalence, clinical presentation, treatment, and outcomes of patients with CRS in our renal transplant cohort. Methods: Charts and medical records of adult RTR were investigated to identify patients with renal allograft dysfunction and heart failure (HF) with reduced (HFrEF) or preserved (HFpEF) ejection fraction. Results: From December 2009 to December 2019, a total of 1,610 patients received a kidney allograft at our institution. CRS was diagnosed in 9 patients (0.56%) a median of 11 years after transplantation (4–20 years). Seven of the patients were male, and 2 were female. The median age when CRS was diagnosed was 71 years (64–80 years). The major presenting symptom was dyspnea. Five patients had HFrEF, and 4 had HFpEF. The patient’s median basal creatinine clearance was 37 mL/min (range 29–77 mL/min). At hospitalization, it was decreased to 24 mL/min (range 13–45 mL/min). The patients were treated with diuretics, but 5 of them required extracorporeal fluid removal. At the 16-month follow-up (median), all patients with HFpEF were alive and had returned to initial levels of creatinine clearance. Two of the 5 HFrEF had died, and 2 needed permanent extracorporeal water removal. Conclusion: CRS after renal transplantation was rare (

Current knowledge on histopathological changes occurring after COVID‐19 in transplanted kidneys is limited. Herein, we present renal allograft pathology findings in patients recovered from COVID‐19. Six patients underwent indication biopsy, and one required allograft nephrectomy after acute COVID‐19. Demographic data, clinical characteristics, and laboratory findings were recorded. The histopathological analysis included light microscopy, immunostaining, and electron microscopy. Five patients were hospitalized for acute COVID‐19, and all were diagnosed with imaging‐confirmed pneumonia, one requiring mechanical ventilation, and two requiring dialysis. Two patients had mild form. Histopathologic examination of renal allograft specimens revealed collapsing, perihilar, tip‐lesion and secondary FSGS in one patient each. One patient had borderline acute cellular rejection, and two had chronic antibody‐mediated rejection. Histopathologic changes of glomerular tufts were accompanied by acute tubular injury in four patients. None of our patients had signs of viral inclusions in kidney cells. One patient died and one remained dialysis‐dependent after the good initial response to treatment. Patients with collapsing and perihilar FSGS had further progression of their chronic allograft nephropathy still without need for dialysis. In conclusion, diverse kidney pathology may be found in SARS‐CoV‐2–infected renal transplant patients. It seems that viral infection may affect the immune system with triggering of glomerular diseases, while the acute tubular injury is of multifactorial etiology. Direct viral effect is less likely.

Infectious pathogens have been linked to the genesis of malignancy in a variety of different settings. Initial studies in virology led to the important discovery of key genetic alterations underlying common malignancies, and further, lent support to the notion that malignancy can be promoted by the process of viral infection and cellular transformation. In this review, we summarize a series of hematologic malignancies with derivations from and associations with infectious organisms. Among these are a variety of lymphomas, including Hodgkin's lymphoma (Hodgkin's disease), Burkitt lymphoma, and a host of other non-Hodgkin's lymphomas. Through innovative and ground-breaking studies, some of these malignancies have been directly linked to viral infection, such as the Epstein-Barr virus (EBV), while others have been merely associated with infection through epidemiologic studies and case-reports. Some malignancies have been demonstrated to be caused by viral infection, such as adult T-cell leukemia and lymphoma (ATLL), which is caused by the human T cell lymphotropic virus type I (HTLV-I), in certain endemic area. In the future, additional malignant states may be found to be associated with infectious etiology, which could allow for novel approaches to prevention and treatment.

International audience; Although the gold standard of monitoring kidney transplant function relies on glomerular filtration rate (GFR), little is known about GFR trajectories after transplantation, their determinants, and their association with outcomes. To evaluate these parameters we examined kidney transplant recipients receiving care at 15 academic centers. Patients underwent prospective monitoring of estimated GFR (eGFR) measurements, with assessment of clinical, functional, histological and immunological parameters. Additional validation took place in seven randomized controlled trials that included a total of 14,132 patients with 403,497 eGFR measurements. After a median follow-up of 6.5 years, 1,688 patients developed end-stage kidney disease. Using unsupervised latent class mixed models, we identified eight distinct eGFR trajectories. Multinomial regression models identified seven significant determinants of eGFR trajectories including donor age, eGFR, proteinuria, and several significant histological features: graft scarring, graft interstitial inflammation and tubulitis, microcirculation inflammation, and circulating anti-HLA donor specific antibodies. The eGFR trajectories were associated with progression to end stage kidney disease. These trajectories, their determinants and respective associations with end stage kidney disease were similar across cohorts, as well as in diverse clinical scenarios, therapeutic eras and in the seven randomized control trials. Thus, our results provide the basis for a trajectory-based assessment of kidney transplant patients for risk stratification and monitoring.

Kidney donor with Down syndrom.

Introduction Although most patients recover within several weeks after acute COVID‐19, some of them develop long‐lasting clinical symptoms. Renal transplant recipients have an increased mortality risk from COVID‐19. We aimed to describe complications occurring after COVID‐19 in this group of patients. Methods A prospective single‐center cohort study was conducted at University Hospital Centre Zagreb. Patients with two negative reverse transcriptase‐polymerase chain reaction (RT‐PCR) tests for SARS‐CoV‐2 after COVID‐19 were eligible for further follow‐up at our outpatient clinic. They underwent detailed clinical and laboratory assessments. The primary outcome was the development of complications after COVID‐19. Results Only 11.53% of renal transplant recipients who survived acute COVID‐19 were symptomless and free from new‐onset laboratory abnormalities during the median follow‐up of 64 days (range: 50–76 days). Three patients died from sepsis after discharge from the hospital. In 47 patients (45.2%), clinical complications were present, while 74 patients (71.2%) had one or more laboratory abnormalities. The most common clinical complications included shortness of breath (19.2%), tiredness (11.5%), peripheral neuropathy (7.7%), self‐reported cognitive impairments (5.7%), and dry cough (7.7%). Most common laboratory abnormalities included shortened activated partial thromboplastin time (50%), elevated D‐dimers (36.5%), elevated fibrinogen (30.16%), and hypogammaglobulinemia (24%). Positive RT‐PCR for cytomegalovirus (8.7%), Epstein–Barr virus (26%), or BK virus (16.3%). Multivariate analysis identified the history of diabetes mellitus and eGFR CKD‐EPI as predictors for the development of post‐COVID clinical complications. Six months after acute COVID‐19, elevated D‐dimers persisted with normalization of other laboratory parameters. Twenty‐nine patients were hospitalized, mostly with several concomitant problems. However, initially reported clinical problems gradually improved in the majority of patients. Conclusion Post‐COVID‐19 clinical and laboratory complications are frequent in the renal transplant population, in some of them associated with significant morbidity. All patients recovered from acute COVID‐19 should undergo long‐term monitoring for evaluation and treatment of complications., Although most patients recover within several weeks after acute COVID‐19, some of them develop chronic injury of different organs or have nonspecific long‐lasting clinical symptoms. Renal transplant recipients have clinical and laboratory complications after acute COVID‐19.

Background The aim of this study is to determine the incidence, etiology, clinical characteristics, and outcomes of renal transplant recipients diagnosed and treated for central nervous system (CNS) infection at our institution. Methods We analyzed data from all renal transplant recipients between January 2007 and December 2019 that were diagnosed and treated for CNS infections at our institution. Results Of 1374 patients who received renal allografts, 13 were diagnosed with CNS infections (9 males), with a mean age of 53.5 years. Patients were diagnosed with CNS infections between 2 months and 11 years after the transplantation. Causative agents included JC virus, Streptococcus pneumoniae, Cryptococcus neoformans, Herpes zoster virus, Mycobacterium tuberculosis, Listeria monocytogenes, and West Nile virus. One patient had concomitant Nocardia and Neisseria infection. Immunosuppression was reduced in all patients. The patient with JC encephalitis and the patient with concomitant Neisseria and Nocardia meningitis died. One patient was returned to dialysis. Other patients recovered with differing levels of neurologic sequelae. Conclusion Central nervous system infections in renal transplant recipients are rare. However, they are associated with significant morbidity and mortality. A high level of awareness is needed: neurological symptoms may be nonspecific and caused by non-infectious conditions related to the underlying disease, or side-effects of immunosuppressive drugs.

Invazivni gljivični sinusitis je rijedak u populaciji bolesnika s transplantiranim bubregom. Postoji tek nekoliko izvještaja koji ukazuju na složenost problema dijagnostike, liječenja i praćenja bolesnika. Šezdesetpetogodišnji bolesnik pet godina nakon transplantacije bubrega razvija infekciju paranazalnih sinusa sporo progresivnog tijeka. Obradom se pronađe destrukcija tkiva oko zahvaćenog paranazalnog sinusa, a mikrobiološki se potvrdi Aspergillus fl avus rezistentan na amfotericin B, uz Aspergillus sclerotiorum, soj osjetljiv na vorikonazol. Provede se terapija vorikonazolom uz redukciju imunosupresije. Opetovani relapsi bolesti su zahtijevali dugotrajnu primjenu vorikonazola, a potom zbog razvoja rezistencije, i kaspofungina. Bolesnik je na posljednjoj kontroli dobrog općeg statusa, bez znakova infektivnog zbivanja uz očuvanu funkciju presatka. Zaključno, aspergiloza paranazalnih sinusa je rijetka u populaciji bolesnika s transplantiranim bubregom. Rana dijagnoza, agresivni kirurški pristup s odstranjivanjem nektoričnog tkiva i dugotrajna antifungalna terapija povećavaju vjerojatnost povoljnog ishoda., Invasive fungal sinusitis is rare in renal transplant population. We present a case of 65-year-old male patient who developed slowly progressive rhinosinusitis with tissues destruction. Amphotericine B resistant Aspergillus fl avus and voriconasole sensitive Aspergillus sclerotiorum were isolated as causative pathogens. Voriconasole therapy was initiated along with reduction of the immunosuppression. Frequent disease relapses required prolonged voriconasole treatment, which was later switched to caspofungine because of development of resistance. At the last outpatient control, he was stable, without infective symptoms, with stable renal allograft function. In conclusion, paranasal sinuses aspergillosis is rare in renal transplant recipients. Early diagnosis with aggressive surgical treatment and resection of necrotic tissue, accompanied with the long term antifungal therapy increases the probability of favourable outcome.

Završni stadij kronične bubrežne bolesti zahtijeva liječenje nadomještanjem bubrežne funkcije različitim metodama, od kojih je najbolja transplantacija bubrega, zbog značajno više stope preživljavanja i kvalitete života u usporedbi s dijalizom. U početcima transplantacijske medicine, kada su transplantacije izvođene samo u mlađih pacijenata, a preživljenje presatka bilo relativno kratko zbog visoke stope akutnih odbacivanja, zloćudni tumori predstavljali su manje važan problem. Vodeći uzrok gubitka presatka u vrijeme suvremene imunosupresije je smrt pacijenata s funkcionirajućim presatkom, a upravo su zloćudni tumori, nakon srčanožilnih bolesti i infekcija, na trećem mjestu uzročnika smrti u populaciji pacijenata s transplantacijom koja je sve starija i pod sve dužim kumulativnim djelovanjem imunosupresiva. Prema podatcima Registra za transplantaciju Australije i Novog Zelanda 10 % pacijenata razvije tumor nakon 10 godina, 25 % nakon 20 godina, a nakon 30 godina čak 40 % primatelja bubrega pod imunosupresivnom terapijom razvije tumor. U kohorti od 175 000 primatelja u Sjedinjenim Američkim Državama je identificirano 10 656 tumora, što je 2,1 puta više nego u općoj populaciji. Uočen je značajan porast rizika za više od 30 različitih primarnih tumora te snižena incidencija tumora dojke i prostate u odnosu na opću populaciju., End-stage renal disease requires the replacement of kidney function by different methods, the best of them being renal transplantation owing to significant survival advantage and better quality of life compared to the dialysis. In the beginnings of transplantation medicine, when transplantation was performed solely in young patients, and survival was relatively short due to acute rejections, malignant tumors were not a significant problem. In the era of modern immunosuppression, the leading cause of graft lost is death of a patient with functional graft. Malignant tumors are the third leading cause of death in patients following renal transplantation due to the increasing age of patients undergoing renal transplantation and longer cumulative influence of immunosuppression. Cardiovascular diseases and infections are the first and a second leading cause of death, respectively. According to Australian and New Zealand Dialysis and Transplant Registry, 10% of patients develop tumor 10 years after transplantation, 25% after 20 years, and after 30 years 40% of renal transplant recipients treated with immunosuppression develop malignancy. In a large population-based cohort study of 175 000 United States transplant recipients of solid organs, among those 10 656 developed some kind of a tumor. This is 2.1 times more often when compared to the general population. A significant increase of risk for 30 different primary tumors was reported, whereas a decreased incidence of breast cancer and prostate cancer was noted.

John Cunningham (JC) virus is a well-known cause of progressive multifocal encephalopathy. Only a few cases of polyomavirus-associated nephropathy due to JC virus have been reported so far. We report one such case in a kidney transplant recipient who presented with proteinuria and increased serum creatinine. Allograft biopsy revealed polyoma virus-associated nephropathy. Real-time polymerase chain reaction revealed negative result for BK and JC virus in the blood, negative for BK virus and positive for JC virus in the urine, and fi nally, when performed on the biopsy sample it detected more than 106 copies of JC virus DNA, which allowed us to establish JC virus-associated nephropathy as a defi nitive diagnosis. The patient was treated with intravenous immunoglobulins and reduction of immunosuppression. Serum creatinine returned to initial levels with decrease of proteinuria. This case documents that JC virus may cause signifi cant changes in renal allograft and should be included in the differential diagnosis of allograft dysfunction., Dok je John Cunningham (JC) virus dobro poznati uzročnik progresivne multifokalne encefalopatije, dosad je opisan kao uzročnik nefropatije u tek nekoliko slučajeva. Prikazujemo bolesnika s transplantiranim bubregom koji se prezentirao proteinurijom i porastom serumskog kreatinina. Biopsijom presatka je dokazana poliomavirusna nefropatija. Uporabom lančane reakcije polimeraze BK virus i JC virus su bili negativni u krvi, u mokraći je BK virus bio negativan, a JC virus pozitivan, dok je iz bioptata dokazano više od 106 kopija DNA JC virusa, čime smo potvrdili dijagnozu nefropatije presatka uzrokovane JV virusom. Bolesnik je liječen intravenskim imunoglobulinima uz smanjivanje intenziteta imunosupresije. Ovaj bolesnik potvrđuje da JC virus može uzrokovati značajne promjene u bubrežnom presatku i da ga treba uključiti u diferencijalnu dijagnozu pogoršanja funkcije presatka.

Pandemija COVID-19 paralizirala je transplantacijske programe širom svijeta, uz visoke stope smrtnosti u populaciji bolesnika s transplantiranim bubregom. Suočeni s nepoznatim patogenom svjedočimo čitavom nizu manje ili više uspješnih pokušaja liječenja. Bolesnici s transplantiranim bubregom su posebno ugrožena skupina s obzirom na kronično stanje imunosupresije. Dodatan problem u liječenju COVID-19 predstavlja problem mogućih interakcija lijekova koji se rabe u liječenju SARS-CoV-2 s imunosupresivima, kao i rizik akutnih odbacivanja prilikom značajnih smanjivanja imunosupresije. Ponovno oživljavanje transplantacijskih programa zahtijevat će pažljivu procjenu rizika i dobrobiti za svakoga pojedinog bolesnika uz promišljanje načina uspostave međunarodne razmjene organa. Potrebna su daljnja istraživanja kako bi se odredio optimalan način liječenja SARS-CoV-2 u bolesnika s transplantiranim bubregom., The COVID-19 pandemic has paralyzed renal transplant programs worldwide, with high mortality rates in renal transplant patients. Faced with an unknown pathogen, we have witnessed numerous treatment attempts that have been more or less effective. Renal transplant recipients are at increased risk for morbidity and mortality from COVID-19 given their chronic immunocompromised state. Additional complications are potential interactions in drugs used for treatment of SARS-CoV-2 and immunosuppressive medications, as well as risk of acute allograft rejection associated with reduction of immunosuppression. The revival of renal transplant programs will require careful assessment of individual risk-to-benefit ratio for each patient, with step-by-step reintroduction of international organ exchange. Further studies are needed to determine optimal treatment of SARS-CoV-2 in renal transplant recipients.

Case description

Non-thyphoidal Salmonella usually presents as gastroenteritis while extra-intestinal manifestations are rare and mostly occur in patients with predisposing conditions such as chronic illness, urinary tract abnormalities, and immunosuppression. Urinary tract infection is the most common infectious complication in kidney transplant recipients. There are very few cases of urinary tract infections caused by non-thyphoidal Salmonella in kidney transplant recipients in the English literature, and to the best of our knowledge, only nine cases being stool negative. Although being extremely rare, non-thyphoidal Salmonella should be considered as one of the possible causes of urinary tract infections in kidney transplant recipients even without concomitant or preceding gastrointestinal symptoms. Bacteriuria can be present for some time after treatment requiring prolonged treatment and urine culture surveillance., Gastroenteritis je najčešća posljedica infekcije netifoidnom salmonelom. Ekstraintestinalne manifestacije su iznimno rijetke i najčešće se viđaju u bolesnika s predisponirajućim stanjima kao što su kronične bolesti, bolesti urotrakta i stanja povezana s imunosupresijom. Infekcije mokraćnih putova su najčešća infektivna komplikacija u bolesnika s transplantiranim bubregom. U literaturi je do sada opisano svega nekoliko slučajeva infekcija mokraćnih putova uzrokovanih netifoidnom salmonelom, a u samo devet slučajeva bakterija nije dokazana i u uzorcima stolice. Netifoidna salmonela je iznimno rijedak, no moguć uzročnik infekcija mokraćnih putova u bolesnika s transplantiranim bubregom, čak i u slučajevima bez pridružene ili prethodne kliničke slike gastroenteritisa. Nakon provedenog liječenja može zaostati asimptomatska bakteriurija pa je nakon završetka liječenja potrebno redovito uzimati nadzorne urinokulture.

Case description

Primatelji solidnih organa imaju 3-4 puta veću pojavnost zloćudnih tumora, no osim tumora vlastitog tkiva, primatelji organa mogu razviti i zloćudnu bolest povezanu s darovanim organom. Prema istraživanjima izvan Republike Hrvatske, udio bolesnika koji razviju zloćudni tumor prenesen s darovatelja iznosi 0,01-0,05 %, što bi u hrvatskim uvjetima značilo 0,02-0,1 bolesnika s prenesenim zloćudnim tumorom godišnje. Rizičnima za prijenos tumora smatraju se darovatelji stariji od 45 godina te oni s preboljelim zloćudnim tumorom u anamnezi. Jasne smjernice još nisu razvijene pa svakom bolesniku treba pristupiti individualno i procijeniti rizike i boljitke postupaka. Četiri slučaja transplantacije bubrega s moždano-mrtvog darovatelja za koje se autopsijom doznalo za malignu bolest zabilježena su i na KBC-u Zagreb., It is known that the incidence of malignant diseases is increased 3 to 4 times when the population of solid organs recipients is observed. Apart from the tumours developed from one's own tissues, tumour recipients may develop a malignant tumour related to the donated organ. The chance of developing such a disease is far smaller than the one of developing a malignant disease originating from one's own tissues but the chance is not non-existant. It is necessary to examine whether such a risk is worth taking and whether the donated organ should be explanted in the case of discovering a malignancy in donor. Another problem is the fact that a portion of such tumours is discovered not before the deceased donor's obduction. Acorrding to researches outside of Croatia, 0,01-0,05% of kidney recipients develop a malignancy transmitted from the donor. In Croatian terms, that would be equivalent to 0,02-0,1 persons per year. Increased risk groups would be donors over the age of 45 and donors with a history of malignant disease. There are no clear guidelines developed yet but there are some widely-accepted procedures in certain situations. Each patient must be individually evaluated and cost-benefit analysis must be taken into account. Four cases occured in the Hospital University Center Zagreb when the autopsy discovered a malignancy in kidney donors.

There is limited data on multiple primary malignancies in the kidney transplant population. Gastrointestinal stromal tumors (GISTs) are rare tumors in kidney transplant recipients, with only 5 cases reported in the literature to date. GIST patients are at an increased risk for developing additional malignancies, with other histologic types of gastrointestinal tract malignancies being the most frequent and other types of malignancies rare. There is evidence in the literature suggesting an association between GIST and renal cell carcinomas. We report on the first case of a GIST and a renal cell carcinoma in a kidney transplant recipient and in other solid organ transplant recipients.

The present study analyzed growth and longevity of the endemic cave dwelling bivalve Congeria kusceri obtained from the pit Jama u Predolcu, Croatia. A water temperature of 13–14°C constituted the lower limit for shell growth of C. kusceri. Obtained data also indicated that enhanced calcium uptake by C. kusceri during its summer growth and reproductive phases coincided with a decrease in alkalinity of the pit water. An analysis of shell growth rings in C. kusceri has identified an impressive longevity of 53 years. Calculations of growth rate suggested maximum theoretical shell lengths (L∞) of 16.7 mm for males and 18.7 mm for females and a growth constant of 0.04 year-1 for both sexes. Congeria kusceri can, however, grow to a shell length of > 24 mm, suggesting that longevity of this species could be greater than that identified in this study. The obtained results add to our understanding of how colonisation and continued and successful occupation of a subterranean freshwater habitat has been ach...

Primary cardiac hemangioma is a very rare benign vascular tumor, with valvular hemangiomas being even less frequent as valves are generally avascular structures. We present the first case of mitral valve hemangioma in a renal transplant recipient. Patient presented with progressive dyspnea. Transesophageal echocardiogram (TEE) demonstrated a 0.8x0.9-cm pedunculated tumor mass on the posterior leaflet of the mitral valve. Coronary angiography identified a small artery which filled from the circumflex artery and fed the tumor. The tumor was surgically removed. Histopathological examination revealed a hemangioma. The postoperative course was uneventful with stable graft function.

Propionibacterium acnes is a gram-positive human skin commensal that is involved in the pathogenesis of acne and prefers anaerobic growth conditions. It has been considered as a low virulence pathogen in different clinical conditions. We present the case of acute peritonitis caused by Propionibacterium acnes in a peritoneal dialysis patient.

BACKGROUND: The Eurotransplant "senior" program allocates kidneys from elderly donors to patients >65 years old. It aims to increase the number of renal transplantations. Kidneys are allocated locally without human leukocyte antigen (HLA) matching to decrease the cold ischemia time. Croatia has introduced its own "senior" program based on HLA matching. We compared results with those from Eurotransplant. ----- METHODS: We identified and prospectively followed all patients aged of >/=65 years who underwent a first renal transplantation. We recorded their HLA matching, cold ischemia time, renal function, surgical and medical complications, and duration of hospitalization. ----- RESULTS: Through October 2007, 22 elderly patients received an allograft from donors who were >65 years old. There were 8 female and 14 male patients of mean age at transplantation of 67.4 years. Mean donor age was 66 years. The number of HLA mismatches ranged from 1 to 5, and cold ischemia time from 7 to 15 hours. One-year patient survival was 95.4%, and graft survival was 81.8%. Delayed graft function, defined as the need for dialysis for >7 days after transplantation, occurred in 63.6% of patients. Older recipients required prolonged hospitalization after transplantation (45 days; range, 16-131). Frequent posttransplant complications included posttransplant diabetes mellitus in 1 patient, delayed wound healing in 5 patients, and lymphocoel in 2 patients. Maligancies occurred in 3 patients, neoplasm of the native kidney, posttransplant lymphoproliferative disease, and skin cancer. One patient experienced acute rejection that was successfully treated with steroids. Seventeen patients experienced 20 viral infections. There was only 1 serious infection (pulmonary tuberculosis). The major problems were cardiovascular complications which occurred in 40.9% of patients. ----- CONCLUSION: Renal transplantation in elderly patients is associated with increased incidence of posttransplant surgical and medical complications which demand prolonged hospitalization. Incidence of acute rejections in elderly patients is significantly decreased with HLA matching, without prolongation of the cold ischemia time. Good results justify renal transplantation in this group of patients.

Background. Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial disease prevalent in Croatia, Romania, Bulgaria, Bosnia and Herzegovina, and Serbia. In addition to renal disease, an increased incidence of upper urothelial carcinomas (UUCs) has been observed in the foci of BEN. Carcinoma may occur alone or in combination with BEN. Immunosuppression is associated with an increased risk for development of different malignancies. There are no data in the literature about the outcome of patients with BEN after transplantation. Methods. We performed a retrospective evaluation of the database and review of the charts and pathology reports of 601 renal transplant recipients treated at our institution. Results. From January 1995 to December 2004, kidney transplantations were performed in nine patients with BEN. One-year graft survival was 100%. A man, who was transplanted in 1997 died 2 years after transplantation with a functioning graft due to disseminated cancer from the pelvis of his own kidney. A female patient developed UCC 2 years after transplantation. They were both treated with a bolus of methylprednisolone before transplantation, because of four HLA-mismatches. A male patient developed UCC in the native and transplanted kidneys. He underwent a native nephroureterectomy with partial nephroureterectomy of transplanted kidney. His graft function was preserved with decreased immunosuppression. Three years later a urinary bladder carcinoma was discovered on a regularly performed multislice computed tomography. One patient developed a skin malignancy. Other patients have had uneventful posttransplantation courses with excellent graft function. Thus, 33.3% of patients with BEN developed UUC, compared with a 0.67% prevalence of urinary tract tumors among transplanted patients with other causes of end-stage renal disease. Conclusion. Patients with BEN are at increased risk for the development of UCC after transplantation. Regular screening for early detection of malignancy is mandatory. Longer follow-up and results from other transplant centers are needed to further investigate the relationship between BEN and UCC after renal transplantation.

The balance and quality of different renal replacement treatment modalities used in the elderly with end-stage renal disease vary between countries depending on economic resources, distribution of renal units, number of specialists, and patterns of reimbursement of both hospitals and physicians. Elderly patients with end-stage renal disease need detailed assessment of medical, psychological, motor, and social factors in order to choose an appropriate renal replacement treatment option. Presence or absence of significant comorbidity is much more important than the chronological age. The choice between hemodialysis and continuous ambulatory peritoneal dialysis is largely dependant on preferences of the local team and the patient. Patients with adequate cardiovascular systems are generally considered to be more suitable for hemodialysis. Hemoglobin should be optimized (Hb between 100 and 120 g/L) in all patients. Poor cardiac status and/or angina will require assessment, medical treatment, and, if necessary, surgical treatment or angioplasty. Transplantation should be considered in all reasonably fit and carefully selected patients older than 65 or even 70 years. Only the permanent shortage of suitable kidneys limits our ability to treat all those who could benefit from this type of treatment. Renal transplant recipients may benefit in terms of both survival and quality of life even if older than 70 years and beyond. Immunosuppressive therapy in elderly patients should be moderate.

First case of endometrial carcinoma caused by tamoxifen.

Patients with chronic kidney disease (CKD) and specially end-stage renal disease (ESRD) have markedly advanced vascular disease when compared to the general population. In particular, several authors have reported more severe atherosclerotic disease of the carotid arteries among ESRD patients than in subjects with normal renal function. This accelerated disease of the cerebral vasculature could increase the risk of ischemic stroke in these patients. Additionally, ESRD is associated with hypertension, a bleeding diathesis, and the routine administration of heparin during hemodialysis, which could increase the risk of hemorrhagic stroke. Dialytic support, including both hemodialysis (HD) and peritoneal dialysis, have been shown to be risk factors for stroke. No studies have assessed stroke risk in renal transplant recipients. Although there are some epidemiologic data for stroke in patients with CKD, there are fewer data for stroke treatment in patients with CKD. In primary and secondary prevention of stroke even in the CKD patients, it has been well established that improved outcomes occur by correcting reversible risk factors, including treating hypertension, secondary hyperparathyroidisam, anemia, dyslipidemia, coagulation abnormalities, malnutrition, inflammation, controlling diabetes, and cardiac disease.

The principal iron storage protein is ferritin, which is primarily present in cytoplasm. The most common cause of hyperferritinemia is iron overload, which is either primary or secondary. Hyperferritinemia is commonly found in patients with chronic kidney disease regardless of their hemoglobin level and is often considered to be related to chronic inflammatory status as well as malnutrition and neoplasias. We present a case of a kidney transplant patient that developed severe hyperferritinemia associated with liver dysfunction. In our patient, high hyperferritinemia was detected a year after transplantation, when she had no signs of inflammation. Malignancies, chronic viral hepatitis, and chronic inflammatory disease were also excluded as the causes of hyperferritinemia. Since high serum ferritin levels were combined with increased transferrin saturation and mildly elevated plasma iron concentrations, we presume that the most probable cause of hyperferritinemia in our patient was iron overload.

Sada dvadesetjednogodišnja bolesnica od 2001. godine zna da ima potkovasti bubreg. Od travnja 2005. godine se liječi peritonejskom dijalizom. U lipnju 2009. učinjena je transplantacija bubrega s umrle osobe, ali je dva mjeseca kasnije bilo neophodno učiniti graftektomiju zbog teške gljivične infekcije uz razvoj akutnog odbacivanja presatka. Bolesnica je vraćena na peritonejsku dijalizu. U ožujku 2011. učinjena je druga transplantacija uz dobru funkciju presatka. Devet mjeseci kasnije dolazi do razvoja ascitesa uz difuzne bolove u abdomenu. MSCT-om se verificira opsežni skleroziraju i peritonitis uz dilataciju terminalnog ileuma do 9 cm, a distalnije od distenzije nađeno je 25-30 cm terminalnog ileuma u bloku. Unatoč parenteralnoj prehrani stanje bolesnice se pogoršavalo te se u travnju 2012. godine pristupilo kirurškom zahvatu. Medijanom laparotomijom nađe se tanko crijevo prekriveno vrstom fibroznom pločom uz opsežne priraslice. Učini se opsežna adhezioliza s lateralnih strana u području retroperitoneuma prema sagitalnoj liniji. Presiječe se ileum ispred opisanog bloka otprilike 25-30 cm od ileocekalne valvule, a potom se presiječe i transverzum i formira laterolateralna anastomoza terminalnog ileuma i transverzuma produženim šavom u dva sloja. Postavi se abdominalni dren. Postoperativni tijek se komplicira febrilitetom pa se osam dana nakon prvog kirurškog zahvata učini eksplorativna relaparotomija i evakuira sadržaj iz apscesne šupljine. Bolesnica je liječena antibioticima širokog spektra, a zbog zatajivanja funkcije presatka i hemodijalizom. Nakon mjesec dana bolesnica ponovno postaje febrilna, MSCT-om se postavi sumnja na apsces, ali se eksplorativnom laparotomijom ne nađe kolekcija u abdomenu. Ponovno očitanje MSCT-a pokazalo je da se radi o edematoznom transplantiranom bubregu. Učini se graftektomija. Bolesnica se dobro oporavila i nastavila liječenje hemodijalizom u matičnom centru., A 21-year-old female patient was diagnosed with horseshoe kidney at the age of 10. She had been treated with peritoneal dialysis from 2005 to 2009, when she received kidney from a deceased donor. The posttransplant course was complicated by development of Pseudomonas aeruginosa and Candida sepsis. Reduced immunosuppression resulted in acute rejection, which demanded graphtectomy 2 months after transplantation. She restarted peritoneal dialysis for additional 2 years. In March 2011, she received her second transplant with excellent function. Nine months after the transplantation, she developed ascites, with early satiety and vomiting. MSCT revealed severe encapsulating sclerosing peritonitis. Her overall condition deteriorated, so she underwent adhesiolysis with resection of incarcerated terminal ileum. Due to acute allograft rejection, urgent graphtectomy was performed. Currently, she is receiving everolimus and dialysis successfully, with excellent overall status.

Između pojedinih zemalja postoje velike razlike u kvaliteti i dostupnosti različitih oblika bubrežne nadomjesne terapije za osobe starije životne dobi. Razlike ovise o postupku liječenja, ekonomskim izvorima, raspoređenosti centara za skrb nad bubrežnim bolesnicima, broju specijalista i razini stručnosti bolnica i liječnika. Nadomještanje bubrežne funkcije u starijih osoba zahtijeva procjenu medicinskih, psiholoških, motoričkih i socijalnih faktora kako bi se odredio optimalan način liječenja. Postupak procjene mora biti standardiziran kako bi se osigurala objektivnost. Kronološka dob ima mnogo manje značenje od pridruženih bolesti. Izbor između hemodijalize i kontinuirane ambulatorne peritonejske dijalize uglavnom ovisi o tome kojoj od metoda bolesnik i lokalni centar za dijalizu daju prednost. Bolesnici sa zdravijim srčano-krvožilnim sustavom općenito su prikladniji za liječenje hemodijalizom. U svih bolesnika hemoglobin treba održavati u rasponu od 100 do 120 g/L. Srčanim bolesnicima treba osigurati dijagnostičku obradu i liječenje, bez obzira da li se radi o konzervativnim ili agerivnijim kardio-kirurškim zahvatima. U bolesnika koji su stariji od 65 godina i odabranih bolesnika starijih od 70 godina koji nemaju kontraindikaciju, treba napraviti transplantaciju bubrega. Ograničavajući čimbenik u liječenju svih onih koji bi mogli imati korist od ovog oblika liječenja je trajni nedostatak bubrega prikladnih za transplantaciju. Presađivanje bubrega ima pozitivne učinke kako na preživljenje tako i na kvalitetu života za odabrane primatelje do 70-te godine života i starije. Imunosupresija treba biti umjerena., The balance and quality of different renal replacement treatment modalities used in the elderly with end-stage renal disease vary between countries depending on economic resources, distribution of renal units, number of specialists, and patterns of reimbursement of both hospitals and physicians. elderly patients with end-stage renal disease need detailed assessment of medical, psychological, motor, and social factors in order to choose an appropriate renal replacement treatment option. Presence or absence of significant comorbidity is much more important than the chronological age. the choice between hemodialysis and continuous ambulatory peritoneal dialysis is largely dependant on preferences of the local team and the patient. Patients with adequate cardiovascular systems are generally considered to be more suitable for hemodialysis. Hemoglobin should be optimized (Hb between 100 and 120 g/L) in all patients. Poor cardiac status and/or angina will require assessment, medical treatment, and, if necessary, surgical treatment or angioplasty. Transplantation should be considered in all reasonably fit and carefully selected patients older than 65 or even 70 years. only the permanent shortage of suitable kidneys limits our ability to treat all those who could benefit from this type of treatment. renal transplant recipients may benefit in terms of both survival and quality of life even if older than 70 years and beyond. immunosuppressive therapy in elderly patients should be moderate.

The principal iron storage protein is ferritin, which is primarily present in cytoplasm. The most common cause of hyperferritinemia is iron overload, which is either primary or secondary. Hyperferritinemia is commonly found in patients with chronic kidney disease regardless of their hemoglobin level and is often considered to be related to chronic inflammatory status as well as malnutrition and neoplasias. We present a case of a kidney transplant patient that developed severe hyperferritinemia associated with liver dysfunction. In our patient, high hyperferritinemia was detected a year after transplantation, when she had no signs of inflammation. Malignancies, chronic viral hepatitis, and chronic inflammatory disease were also excluded as the causes of hyperferritinemia. Since high serum ferritin levels were combined with increased transferrin saturation and mildly elevated plasma iron concentrations, we presume that the most probable cause of hyperferritinemia in our patient was iron overload., Feritin je glavni protein za skladištenje željeza i prvenstveno je prisutan u citoplazmi. Najčešći uzrok hiperferitinemije je preopterećenje željezom, koje može biti primarno ili sekundarno. Hiperferitinemija se često nalazi u bolesnika s kroničnom bubrežnom bolesti bez obzira na razinu njihovog hemoglobina i smatra se da je povezana s kroničnom upalom, pothranjenošću i novotvorinama. Prikazujemo slučaj bolesnice s transplantiranim bubregom u koje se razvila teška hiperferitinemija povezana s jetrenom disfunkcijom. U naše bolesnice hiperferitinemija je otkrivena godinu dana nakon transplantacije, kada u nje nije bilo znakova upale. Zloćudne bolesti, kronični virusni hepatits i kronična upalna bolest su također isključeni kao uzroci hiperferitinemije. Kako je visoka koncentracija feritina bila udružena s povišenom zasićenošću transferina i umjereno povišenom koncentracijom željeza u plazmi, pretpostavljamo da je najvjerojatniji uzrok hiperferitinemije bilo preopterećenje željezom.

Anaemia associated with chronic kidney disease remains a major concern for nephrologists while it significantly increases morbidity and mortality in this patient group. Introduction of erythropoietin has dramatically changed the treatmant of anaemia in uraemic patients. All chronic kidney disease patients with renal anaemia undergoing treatment with an erythropoiesis-stimulating agent (ESA) should be given supplementary iron. Patients undergoing haemodialysis usually have greater iron requirements than those not undergoing dialysis. However, some patients showed hyporesponsiveness to LSE because of inadequate iron supply to the erythroid bone marrow. Intravenous administration is more effective than oral iron supplemantation in renal failure patients. Some studies have raised concerns over the potential serius side-effect associated with the intravenous iron administration. Besides the anaphylactic reactions that were reported to occur in less than 1% of patients treated with iron dextran, and has not been associated with other iron formulations, concerns about long-term use of iron include increased risk of infections and oxidative stress with the consequent cardiovascular disease. Therapy with dextran-free iron formulations is an essential part of anaemia treatment protocols, and was not found to be associated with either short- or long-term serious side-effects.

Ateroskleroza je sustavna bolest koja dovodi do bolesti koronarnih, karotidnih i perifernih arterija. Vodeći je uzrok smrti u razvijenim zemljama. Patofiziologija ateroskleroze ovisi o brojnim urođenim i stečenim čimbenicima. Ključno uporište za nastanak ateroskleroze je gubitak normalne funkcije endotela. Klinička istraživanja dala su brojne dokaze da snižavanje koncentracije lipida može dovesti do korisnih kvalitativnih promjena u atarosklerotskom plaku i povoljno utjecati na kliničko očitovanje bolesti. U aterosklerotskim promijenjenim krvnim žilama česti su kalcifikati koje je moguće radiološki dijagnosticirati, a služe kao pokazatelj težine i ishoda ishemijske bolesti srca. U bolesnika s kroničnim zatajenjem srca, a posebno onih koji su na dijalizi, kalcifikati u koronarnim arterijama čest su nalaz. Najčešće se dovode u vezu s dobi, trajanjem dijalize i dislipidemijom. Liječenjem bolesnika sa zatajenjem bubrega uz pomoć statina i sevelamera moguće je usporiti godišnju progresiju kalcificiranja koronarnih arterija s 30 % na 6 %. Prema podacima iz nekih istraživanja smanjenje koncentracije LDL kolesterola < 2,59 mmol/l može zaustaviti proces odlaganja kalcija ili čak dovesti do njegove regresije. Dodatna istraživanja pokazala su da smanjenje koncentracije LDL kolesterola uz istovremeno povećanje koncentracije HDL kolesterola mogu povoljno utjecati na smanjenje debljine intime i medije karotidnih arterija, kao i na smanjenje veličine plaka u koronarnim arterijama., Atherosclerosis is a systemic disease that is the leading cause of death in the developed world and leads to coronary artery, carotid artery, and peripheral arterial atherosclerotic syndromes. The pathophysiology of atherosclerosis is known to be dependent on multiple hereditary and environmental factors. Loss of normal endothelial function is a fundamental step in the atherosclerotic disease process. A consistent body of evidence from large clinical trails suggests that qualitative changes in plaques contribute importantly to the striking reduction in clinical events produced by lipid lowering. Calcium mineral deposits that frequently accompany atherosclerosis are readily quantifiable radiographically, serve as a surrogate marker for the disease, and predict a higher risk of myocardial infarction and death. Coronary artery calcification is a common observation in chronic kidney disease and end-stage renal disease and is mainly related to age, duration on dialysis, and dyslipidemia. The annual progression of coronary artery calcification can be reduced from 30 % to 6 % with LDL cholesterol reduction caused by statins and possibly sevelamer. At treated LDL cholesterol levels somewhere below 2.59 mmol/l, several sources of data suggest that the anatomic burden of coronary artery disease, including coronary artery calcification, regresses. Additional supportive studies indicate that carotid intima media thickness and the volume of coronary atheroma can also be reduced by LDL cholesterol reduction in concert with elevation of HDL cholesterol.

Racial and ethnic disparities exist in access to kidney transplantation worldwide. The Roma people are often socially deprived, uneducated, and unemployed. We investigated all dialysis centers in Croatia to determine number of Roma people on dialysis as well as their access and reasons for eventual failure to enter the waiting list. There are 9463 registered Roma people in Croatia, however, the estimated number reaches 40,000. Twenty-five Roma patients required renal replacement therapy, giving a prevalence of 830 per million people (pmp), compared with 959 pmp among the general population. Average age at the start of dialysis was 29 vs 67 years; waiting time to kidney transplantation was 48.9 vs 53.5 months; mean age at the time of transplantation was 33.18 vs 48.01 years in Roma versus the general population respectively. One patient received a kidney allograft from a living unrelated spousal donor, and all others from deceased individuals. Patients were followed for 51.5 months (range, 6–240). The most frequent post-transplant complications were urinary tract infections. One patient lost a graft due to severe acute rejection caused by noncompliance. Two young patients were also noncompliant with immunosuppressive medications. One patient died with a functioning graft at 20 years after transplantation due to cardiovascular disease. Among 14 Roma patients currently been treated with hemodialysis in Croatia, 10 are old with clinical contraindications for transplantation; 1 is on the waiting list; 1 left hospitalization for pretransplant evaluation twice; 1 refused evaluation; and 1 is currently being evaluated for the waiting list. The Roma people have excellent access to renal transplantation in Croatia. Many of them refuse evaluation. More efforts should be invested in their education to improve compliance and their post-transplant outcomes.