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Bronchiectasis is a chronic lung disease characterized by an abnormal dilation of the bronchial lumen caused by weakening or destruction of the muscle or elastic components of the bronchial wall, decreased mucous clearance and frequent infections of the respiratory tract. The golden standard for bronchiectasis diagnosis is high-resolution computed tomography (HRCT) of the chest. Inflammation holds a central role in the development of structural lung changes, as well as airway and lung parenchyma damage. Infection and colonization of the respiratory tract contribute to increased inflammation and further damage to the lung. Upon entry into the respiratory tract, the pathogens activate epithelial cells, macrophages and dendritic cells. Activated inflammatory cells secrete chemical mediators which activate the immune response and thus allow the phagocytosis of pathogens. Early diagnosis, appropriate treatment and interruption of the vicious circle between infection and inflammation in patients suffering from bronchiectasis, prevent the development of structural changes to the airways.

Myalgic encephalomyelitis is a complex, multisystem disease with chronic course significantly affecting patients' quality of life. Physical and mental exertion intolerability, muscle pain, and sleep problems are the main features accompanied often with cognitive inefficacy and vegetative symptoms. Prevalence is 7-3000 per 100,000 adults. It is estimated that 90% of the patients are misdiagnosed. Pathogenesis is still only speculative but current research points to disturbances in the immunological system, inflammatory pathways, autonomic and central nervous system, muscle and mitochondria, as well as alterations of gut microbiota and gut permeability. The onset is typically acute, following an infectious disease. Exertional intolerance lasting for more than six months is an important diagnostic factor. The core features must be moderate to severe and present at least 50% of the time. Diagnostic criteria should be fulfilled and differential diagnosis should be made to exclude other potential pathological conditions or to diagnose comorbidities. Brain magnetic resonance imaging morphometry has shown gray matter atrophy in occipital lobes bilaterally, right angular gyrus, and the posterior division of the left parahippocampal gyrus, consistent with memory problems and potentially with impairment of visual processing. Treatment is still symptomatic and of partial benefit. Symptomatic treatment can include medications for controlling pain and sleep problems, graded exercise and cognitive behavioral therapy. Larger controlled trials are needed to shed more light on this challenging condition. Mijalgični encefalomijelitis je složeno, multisistemsko oboljenje sa hroničnim tokom koje značajno utiče na kvalitet života bolesnika. Slaba tolerancija na fizički i mentalni napor, bolovi u mišićima i problemi sa spavanjem glavne su odlike i često su praćene kognitivnom neefikasnošću i vegetativnim simptomima. Prevalencija je 7-3000 na 100.000 odraslih. Procenjuje se da je 90% ovih bolesnika pogrešno dijagnostikovano. Patogeneza je i dalje samo spekulativna, ali trenutna istraživanja ukazuju na poremećaje u imunološkom sistemu, inflamatornom odgovoru, autonomnom i centralnom nervnom sistemu, mišićima i mitohondrijama, kao i promene mikrobiote i propustljivosti creva. Početak bolesti je tipično akutan i prati infektivnu bolest. Netolerancija napora koja traje duže od šest meseci važan je dijagnostički kriterijum. Osnovne karakteristike moraju biti umerene do teške i prisutne najmanje 50% vremena. Isključivanje drugih mogućih patoloških stanja ili komorbiditetnih dijagnoza zahteva zadovoljavanje dijagnostičkih kriterijuma i diferencijalno dijagnostičko sagledavanje. Morfometrijska snimanja mozga magnetnom rezonancom pokazala su atrofiju sive mase u okcipitalnim režnjevima bilateralno, desnom angularnom girusu i posteriornom levom parahipokampalnom girusu, što može dovesti do problema sa pamćenjem i oštećenja vizuelne obrade informacija. Lečenje je i dalje simptomatsko i samo delimično uspešno. Simptomatski tretman može da uključuje lekove za kontrolu bola i problema sa spavanjem, doziranu fizičku aktivnost i kognitivno-bihevioralnu terapiju. Potrebne su veće studije da bi se razjasnilo ovo medicinsko stanje.

Introduction. COVID-19 pneumonia doesn’t have a characteristic course and prognosis. Many facts still remain hidden, mainly why certain patients develop complications with serious tissue damage and whether it causes a permanent organ impairment. If and when will fibrosis develop in COVID-19 pneumonia requires further research, but a link between the amount of tissue afflicted and the development of fibrosis exists. Case outline. A previously healthy, non-smoker, woman with minor symptoms on admission had suddenly developed a serious respiratory insufficiency and whose radiographic finding on computed tomography scan had shown a serious progression with the development of fibrosis in a matter of days. The exact mechanism and correlation of this clinical course remains unknown; however, it is clear that the pulmonary fibrosis is caused by COVID-19 pneumonia. Follow-up computed tomography scan, performed 50 days after initial symptoms, had shown a partial regression of consolidations and post-inflammatory fibrosis. Conclusion. Pulmonary fibrosis is the most severe complication of COVID-19 infection on the respiratory system. Who, when and if will develop any complication is still unclear, as well as if these changes are reversible? Also, the number of recovered patients who later develop any of the chronic complications remains to be seen.

Introduction. COVID-19 is responsible for the current global pandemic. Globally, over 15 million people are currently infected, and just over 600,000 have died due to being infected. It is known that people with chronic illnesses and compromised immune systems can develop more severe clinical presentation. Tuberculosis (TB) is still one of the biggest epidemiological problems worldwide. Both of these diseases can be misdiagnosed and can manifest in a similar way. We will present a case study of a patient who was initially treated as a COVID-19 infection, with TB being diagnosed later on. The recovery began only after being treated for both diseases simultaneously. Case report. The patient is a 27-year-old male, non-smoker, with no history of any significant diseases. He presented with fever, fatigue and hemoptysis. Computed tomography pulmoangiography had shown massive consolidations and excavations, which could be caused by COVID-19. Despite being treated for COVID-19, there was no clinical improvement. On the follow-up chest X-ray, beside signs of COVID-19, there were also changes that could indicate TB. TB was detected in sputum, using PCR and Mycobacteria Growth Indicator Tube, and only after being treated for both diseases did his condition improve. Conclusion. There are a few reported cases of COVID-19 and TB coinfections, and we believe that there are many more patients with this coinfection being unrecognized

Sarcoidosis afflicts the central nervous system more frequently than previously believed. Neurological symptoms are present in roughly one-half of patients, and depend on the location in the central nervous system. The probability of spontaneous regression is significantly less when compared to other forms of sarcoidosis, which means that the proper diagnosis and treatment is paramount. Even when properly treated, functional defects are not uncommon. Majority of these patients require immunomodulating drugs and continuous follow-up. New immunomodulating drugs, especially biological agents, have shown to be significantly more effective, with fewer side effects, and are important when corticosteroids could not be applied. Less invasive methods, such as cerebrospinal analysis, help greatly in the diagnostics procedure, and require further research and improvement.

Albumin (HSA) is a multifunctional protein and due to its free Cys34 thiol group, represents a main source of free thiols in the circulation. This property of HSA, combined with its ability to sequester redox active Cu(II) ions, makes HSA a dominant circulatory antioxidant. End stage kidney disease (ESRD) is a condition accompanied by elevated oxidative stress. The aim of the present study was to examine changes in the antioxidative capacity of HSA and Cu(II) binding affinity in patients on peritoneal dialysis (PD), and relate it to the Cys34 thiol group content and other structural changes of this molecule. HSA molecules are modified in ESRD patients subjected to PD, having significantly lower thiol group and bound Cu(II) content, reduced antioxidant capacity, an increased content of advanced glycation end-products and altered conformation. Also, Cu(II) binding capacity of HSA in these patients is impaired, since a significant portion of the high-affinity metal-binding site is unable to interact with Cu(II). Taking into account that the concentration of Cu(II) in the circulation of ESRD patients is much higher than in healthy persons and that Cu(II) binding capacity of HSA in these patients is significantly impaired, HSA may be considered as a novel circulatory pro-oxidant, thus exacerbating oxidative stress.

Introduction/Objective Postmortem examination has a significant role in evaluating the quality of health care. The objective of the paper is to analyze the cause of death as determined by postmortem examination in patients who had undergone emergency hospitalization and had subsequently died within 24h, as well as the factors that contributed to the fatal outcome and correlation with available clinical data. Methods the analysis included autopsy reports and protocols, as well as clinical data from medical records and autopsy referrals during the three year period (2018-2020) for patients who had undergone a postmortem examination at the Insitute of Pathology, Medical Faculty, University of Belgrade. The correlation between the clinical diagnosis and postmortem findings was evaluated using Goldman criteria. Results the patients analysed were predominantly male (52/90; 58%). Women were statistically significantly older than men (p=0.024). The most common clinical diagnosis was cardiovascular disease (32.2%). The majority of the patients reported experiencing the first symptoms a few hours before seeking medical help (80%). The majority of the patients were being treated for chronic disease (80%) before hospitalization. The immediate cause of death determined by postmortem examination was most commonly heart failure (38/90, 42.2%). The most common clinically unrecognised causes of death include: bronchopneumonia (8/90), myocarditis (3/90), acute ischemic lesion/acute myocardial infarction (3/90) and bowel infarction (3/90). Conclusion the correlation between clinical and postmortem findings is very important because it enables the discovery of diagnostic and treatment errors and promotes new knowledge crucial for medical advancement.

Introduction/Objective. Due to a very high mortality risk, acute-on-chronic liver failure (ACLF) patients require early identification and intensive treatment. Precise prediction is crucial for determining the urgency degree and therapy appropriateness, considering high mortality and multitude of clinical resources. The aim of our study was to determine the exact cut-off values of various prognostic scores in the prediction of morality of ACLF. Methods. This prospective study includes chronic liver disease (CLD) patients, admitted due to decompensation, that were subsequently diagnosed with ACLF at the Emergency unit. All patients were evaluated based on various prognostic scores, including Child?Pugh, MELD Na, MELD, SOFA, APACHE II, and CLIF C, which were calculated on admission. Results. Alcoholic liver disease (ALD) was the most common underlying CLD cause (77.9%), followed by viral (8.6%), autoimmune (7.7%), and other causes (5.8%). A total of 37.5% of the patients died at the end of the first month of treatment. Average values of Child?Pugh, MELD Na, MELD, SOFA, APACHE II, and CLIF C scores were significantly higher in patients who died compared to survivors (p < 0.05). CLIF C score showed the best performance with a cut-off value of 50.5, with a sensitivity of 94.9% and specificity of 40%. Conclusion. ACLF remains a condition with a high short-term mortality. Of all of the scores examined in our study, CLIF C proved to be the best scoring system for predicting short term and end of treatment mortality in patients with ACLF.

Introduction/aim Clinical signs and symptoms of pulmonary embolism (PE) are non-specific, which is why it is commonly not diagnosed on time or sometimes not diagnosed at all. We are presenting a case of pulmonary embolism manifesting with syncope as a dominant symptom. Case report A 74-year-old female patient was hospitalized at the Clinic for Pulmonary Diseases with PE manifested with syncope. At admission, she was afebrile, tachypneic, with normal cardiac function and normal blood tension. Upon auscultation, breathing was muffled with late inspiration crackles above the base of the left lung. There were no other significant findings. The chest X-ray recorded at admission showed a non-homogenous shadow towards the base of the left lung and minimal pleural effusion. The ECG and echocardiography findings were normal. Partial respiratory insufficiency was verified by the acid-base balance analysis. Inflammatory markers were significantly elevated, with erythrocyte sedimentation rate of 30mm/h, fibrinogen of 8.62g/l and D-dimer of 18.6mg/l. Anticardiolipin IgG and IgM antibodies were negative, as well as beta-2 GPI IgG and IgM antibodies. An MDCT lung angiography was performed because of the elevated values of D-dimer and tachypnea, which showed multiple emboli of various sizes in the distal part of the right pulmonary artery and all lobar branches, as well as an embolus in the lobar branch for the lower lobe of the left lung. After a neurology consult, a head CT was ordered because the patient had suffered from loss of consciousness, but there were no pathological densities in the brain. Colour Doppler Ultrasonography of the blood vessels in the lower extremities showed organized thrombosis of the left femoral vein. A vascular surgeon was consulted and he prescribed anticoagulant therapy and an elastic compressive stocking, with control Colour Doppler Ultrasonography to be performed in six months. Conclusion Although syncope is an easily detectable symptom, it is still an unregulated crossroad of many an internal and neurological disease.

Introduction. Orbit is one of the rarer locations for the metastasis of malignant tumors. The symptoms of orbital tumors are nonspecific, but require detail diagnostics. Methods of visualization, such as ultrasound, radiography, computed tomography scan and/or magnetic resonance imaging of the endocranium are a mandatory step in the diagnostics in order to determine not only the spread of the malignancy but also the affliction of the surrounding structures. The orbital manifestations can be the first sign of the malignant disease. Outline of cases. The first case report presents a female patient with ocular symptomatology as a result of a metastasis of previously undiscovered breast cancer, and the second report presents a male patient with undiscovered lung cancer also presenting with ocular symptomatology. Conclusion. An orbital tumor should instigate further diagnostic procedures, as it can be the first sign of a disseminated malignant disease. [Projects of the Serbian Ministry of Education, Science and Technological Development, Grant no.175046 and Grant no.175081]

Introduction. Gallbladder varices (GBV) represent a rare form of ectopic varices that usually occur in patients with portal hypertension and portal vein thrombosis. Case outline. We present a case of a 38-year-old woman with decompensated autoimmune liver cirrhosis who was referred to our institution for evaluation for liver transplantation. She was incidentally discovered to have GBV during routine B-mode abdominal ultrasonography as part of pre-transplant evaluation. GBV were confirmed by Color Doppler Sonography (CDS), and multi detector computed tomography angiography. Interestingly, portal vein was patent and without thrombus. Conclusion. Despite being asymptomatic in most cases, the presence of GBV is valuable information for a surgeon because they might be a source of potentially catastrophic bleeding, which is particularly poorly tolerated by patients with decompensated liver cirrhosis. Ultrasound has the irreplaceable role not only in discovering GBV, but in prompt diagnosis of before mentioned rare, but unpredictable and fatal complications as well.

Aim Postoperative delirium (PD) is a frequent complication of hip fracture surgery, but its pathophysiology remains poorly understood. We investigated the impact of a single episode of intraoperative hyper/hypotension, blood pressure (BP) fluctuation (ΔMAP), and pulse pressure (PP) on hyper/hypoactive PD in elderly patients undergoing surgery for hip fracture. We also assessed the effect of PD on clinical outcomes. Methods This was a prospective 1-year follow-up study of patients over 60 years of age with a primary diagnosis of acute low-energy hip fracture. Perioperative delirium was assessed using the Confusion Assessment Method (CAM); the development of PD and the type, hyperactive or hypoactive PD, were recorded. Cognitive assessment was evaluated using the Short Portable Mental Status Questionnaire (SPMSQ). The lowest and highest BP values were extracted from the patients’ anaesthesia charts. Postoperative complications, reinterventions and 1-month mortality were recorded. Results PD occurred in 148 (53%) patients during the first postoperative week, with 75% of the cases diagnosed as hypoactive PD. Patients developing PD of any type were older, had a lower body mass index, higher SPMSQ and Charlson scores, more severe systemic diseases, a lower lowest intraoperative BP, a higher ΔMAP, a lower PP, and a higher postoperative pain score. They also took more drugs and received more blood transfusion intraoperatively. Multivariate logistic regression analyses showed that a higher MAP min had a protective effect on the occurrence of any type of PD, as well as hypoactive and hyperactive. PD had negative effect on outcomes. Conclusion Our results provide evidence of an association between maximal hypotension, the lowest intraoperative mean blood pressure (MAP), ΔMAP, PP, and PD. A progressive decrease in MAP during surgery was associated with the increased odds of developing either type of PD.

Vascular calcification (VC) is highly prevalent in dialysis (HD) patients, and its mechanism is multifactorial. Most likely that systemic or local inhibitory factor is overwhelmed by promoters of VC in these patients. VC increased arterial stiffness, and left ventricular hypertrophy. Thus, the present study aimed to investigate the association of VC and myocardial remodeling and to analyze their relationship with VC promoters (fibroblast growth factor 23-FGF23, Klotho, intact parathormon-iPTH, vitamin D) in 56 prevalent HD patients (median values: age 54 yrs, HD vintage 82 months).Besides routine laboratory analyzes, serum levels of FGF 23, soluble Klotho, iPTH, 1,25-dihydroxyvitamin D3; pulse wave velocity (PWV); left ventricular (LV) mass by ultrasound; and VCs score by Adragao method were measured.VC was found in 60% and LV concentric or eccentric hypertrophy in 50% patients. Dialysis vintage (OR 1.025, 95%CI 1.007-1.044, p=0.006) FGF23 (OR 1.006, 95% CI 0.992-1.012, p=0.029) and serum magnesium (OR 0.000, 95%CI 0.000-0.214, p=0.04) were associated with VC. Changes in myocardial geometry was associated with male sex (beta=-0.273, 95% CI -23.967 1.513, p=0.027), iPTH (beta 0.029, 95%CI -0.059-0.001, p=0.027) and vitamin D treatment (beta 25.49, 95%CI 11.325-39.667, p=0.001). Also, patients with the more widespread VC had the highest LV remodeling categories. PWV was associated patient's age, cholesterol, diastolic blood pressure, LV mass (positively) and serum calcium (negatively), indicating potential link with atherosclerotic risk.Despite to different risk factors for VC and myocardial remodeling, obtained results could indicate that risk factors intertwine in long-term treatment of HD patients and therefore careful and continuous correction of mineral metabolism disorders is undoubtedly of the utmost importance.Kalcifikacije krvnih sudova (VC) su prisutne kod velikog broja bolesnika lečenih dijalizom (HD), a njihov nastanak je uslovljen različitim mehanizmima. Postoji mišljenje da promoteri VC prevazilaze lokalni ili sistemski uticajinhibitora VC kod ovih bolesnika. VC povećavaju krutost krvnih sudova i izazivaju hipertrofiju leve komore (LVH). Ova studija je imala za ciljeve da ispita povezanost VC i remodelinga srčanog mišića i da analizira ulogu promotera VC (fibroblast growth factor 23-FGF23, Klotho, intakt parathormon-iPTH, vitamin D) kod 56 prevalentnih HD bolesnika (medijana: starost 54 godine, HD trajanje 82 meseca).Pored rutinskih laboratorijskih analiza, izmereni su FGF 23, Klotho, iPTH, 1,25-dihidroksi vitamin D; brzina pulsnog talasa (PWV); LVH pomoću sonografije; a skor VC je određen Adragao metodom.VC su nađene kod 60% a koncentrična i ekscentrična LVH kod 50% bolesnika. Trajanje HD (OR 1,025, p=0,006), FGF23 (OR 1,006, p=0,029) i S-magnezijum (OR 0.000, p=0,04) bili su udruženi sa VC. Promene u geometriji miokarda su bile udružene sa muškim polom (beta=-0,273, p=0,027), iPTH (beta 0,029, p=0,027) i lečenjem sa vitaminom D (beta 25,49, p=0,001). Bolesnici sa većim VC skorom imali su najviše kategorije LVH. PWV je bila udružena sa starosti bolesnika, koncentracijom holesterola, dijastolnim krvnim pritiskom i LVH (pozitivno) i S-kalcijumom (negativno).Iako su različiti faktori rizika za VC i promene u geometriji miokarda, dobijeni rezultati bi mogli da ukažu na međusobno preplitanje ispitanih faktora kod bolesnika lečenih hemodijalizom. Zbog toga se savetuje pažljiva i stalna korekcija poremećaja u metabolizmu minerala.

Introduction. Pregnancies in women with membranous nephropathy (MN) are usually complicated by increased proteinuria and superimposed preeclampsia, and this frequently results in poor pregnancy outcomes. The aim of this paper is to present case series of pregnant women with MN and different fetal and maternal outcomes. Outline of cases. Case 1 presents a 25-year-old woman with MN, who had relapsed nephrotic syndrome in early pregnancy with proteinuria of 4.14 g/day and serum albumin of 30 g/L accompanied by hypertension. Due to a missed abortion, the pregnancy was terminated. Three months later her proteinuria was still increased, measuring 3 g/day. Case 2 presents a 29-year-old woman with a history of diffuse proliferative glomerulonephritis, who conceived with proteinuria below 0.5 g/day. The proteinuria ranged between 1 and 2 g/day from the 32nd until the 38th gestational week, when she delivered a healthy neonate. After delivery, the woman underwent a kidney biopsy, which revealed MN. Case 3 presents a 25-year-old woman with MN, whose proteinuria was 1 g/day at the time of conception, but in the 35th gestational week proteinuria of 4.2 g/day was noticed. In the 36th gestational week, increased proteinuria was detected, and a cesarean section was performed with favorable neonatal outcome. After two weeks her proteinuria dropped to 0.6 g/day. Conclusion. Pregnancies in women with MN associated with low-grade proteinuria at the time of conception may have a favorable perinatal outcome. Such pregnancies require multidisciplinary management by both obstetricians and nephrologists, and team decision regarding the best timing of delivery.

A simple and reliable method for the determination of the concentration and function of alpha-2-macroglobulin (α2M) by zymography was developed. The method is based on the covalent binding of α2M and trypsin followed by non-reducing PAGE and zymography with gelatine incorporated in the electrophoretic gel. The results showed that α2M binds trypsin in a concentration-dependent manner exhibiting a linear relation. The sensitivity of the method is 125 nM and the intra-assay coefficient of variation 4.2 %. Freezing of α2M induces its partial denaturation, which could be seen as the reduction in the amount of functional molecule and its reactivity with trypsin. The reported method enables measurement of α2M taking into consideration both its quantity and function, stressing the importance of the determination of the amount of physiologically active molecules and not just their presence in the sample. The method was further confirmed using α2M from patients with end-stage renal disease who are known to be under increased oxidative stress and inflammation, which are expected to modify the structure of proteins. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 173042]

OBJECTIVES Our objective was to evaluate the influence of pretransplant risk factors on posttransplant anemia recovery. MATERIALS AND METHODS This single-center observational retrospective study included 80 deceased donor kidney transplant recipients who had been followed up to 16 months after kidney transplant. Time point of posttransplant anemia recovery was considered the time when hemoglobin of 11.0 g/dL was achieved and maintained for 3 consecutive monthly visits. We collected donor/transplant characteristics (age, sex, hypertension history, cause of death, donor kidney function, expanded criteria donor status, deceased donor score, HLA mismatch, and cold ischemia time) and recipient data (pretransplant hemoglobin, parathyroid hormone, kidney graft function, delayed graft function, acute rejection, infections, surgical bleeding, posttransplant parathyroid hormone, iron stores, and C-reactive protein and tacrolimus levels). We used univariate and multivariate Cox proportional hazards analyses and Kaplan-Meier plots to determine associations between variables and posttransplant anemia recovery rate. P < .05 was considered significant. RESULTS We identified 62 deceased donors (33 male; mean age 50 ± 15.1 years) and 80 kidney transplant recipients (52 male; mean age 47.0 ± 10.6 years). Mean pretransplant hemoglobin was 11.4 ± 1.5 g/dL. Donor age, deceased donor score, pretransplant parathyroid hormone, posttransplant transferrin saturation (all P < .05), and tacrolimus level (P < .01) were significantly related to posttransplant anemia recovery. Kaplan-Meier curve identified that recipients of deceased donors below 60 years old achieved hemoglobin of 11.0 g/dL more frequently and earlier than recipients of deceased donors above 60 years old (P < .05). CONCLUSIONS Deceased donor age, deceased donor score, pretransplant serum parathyroid hormone, posttransplant transferrin saturation, and tacrolimus level were significantly associated with posttransplant anemia recovery rate in deceased donor kidney transplant recipients. Anemia recovery was more frequent and earlier in recipients of deceased donors below 60 years than in recipients of donors 60 years old and above.

End-stage renal disease (ESRD) is a condition accompanied by increased inflammation, oxidative stress, risk of cardiovascular complications, and coagulopathies. The structure of fibrinogen and characteristics of fibrin from plasma samples of ESRD patients on peritoneal dialysis (PD) was investigated. Fibrinogen from ESRD patients had a higher degree of carbonylation than fibrinogen from healthy individuals. The Aα chain was the most susceptible to oxidation, followed by the Bβ chain, whereas the γ-chain was the most resistant to oxidation. Spectrofluorimetric analysis suggested a higher extent of modification of amino acid side chains in fibrinogen from ESRD patients. The tertiary structure of fibrinogen was more affected than its secondary structure. The kinetics (time and rate) of fibrinogen coagulation did not differ between the tested groups. Fibrin prepared from the isolated fibrinogen had a similar structure in both groups. Our results confirm that oxidation and structural alterations of fibrinogen occur in ESRD patients on PD, although these modifications produce no direct effect on the fibrin formation. Taking into account that some patients suffer from bleeding, whereas others develop thrombotic complications, further research on this subject is required to identify other components and processes that contribute to the outcome.

Background and Objectives: Abnormal arterial stiffness (AS) is a major complication in end-stage kidney disease (ESKD) patients treated by dialysis. Our study aimed to determine the significance of AS for survival of prevalent dialysis patients, as well as its association with cardiovascular parameters or vascular calcification promoters/inhibitors or both and AS. Materials and Methods: The study involved 80 adult hemodialysis patients. Besides standard laboratory analyses, we also determined promoters and inhibitors of vascular calcification (bone biomarkers): serum levels of fibroblast growth factor 23 (FGF23), soluble Klotho, intact parathormone (iPTH), 1,25-dihydroxyvitamin D3, osteoprotegerin, sclerostin, AS measured as ankle carotid pulse wave velocity (acPWV), Ankle Brachial Index (ABI), and vascular calcification (VC) score. Patients were monitored for up to 28 months. According to the median acPWV value, we divided patients into a group with acPWV &le, 8.8 m/s, and a group with acPWV &gt, 8.8 m/s, and the two groups were compared. Results: Values for bone biomarkers were similar in both groups. Mean arterial blood pressure (MAP), central systolic and diastolic brachial blood pressure, heart rate, and pulse pressure were higher in the group with acPWV &gt, 8.8 m/s than in the group with acPWV &le, 8.8 m/s. The mortality was higher for patients with acPWV &gt, 8.8 m/s at any given time over 28 months of follow-up. In multivariable analysis, predictors of higher acPWV were age &gt, 60.5, higher pulse rate, and higher central systolic or brachial diastolic blood pressure. Conclusions: According to our results, we advise the measurement of acPWV preferentially in younger dialysis patients for prognosis, as well as intervention planning before the development of irreversible changes in blood vessels. In addition, measuring central systolic blood pressure seems to be useful for monitoring AS in prevalent hemodialysis patients.

Glycosylation may strongly affect protein structure and functions. A high risk of cardiovascular complications seen in patients with end-stage renal disease (ESRD) is, at least partly associated with delayed clot formation, increased clot strength, and delayed cloth lysis. Taking into consideration that fibrinogen mediates these processes, we isolated fibrinogen from the plasma from patients with ESRD on peritoneal dialysis (ESRD-PD), and examined glycosylation of native fibrinogen and its subunits by lectin-based microarray and lectin blotting. Compared to healthy controls, fibrinogen from patients had increased levels of A2BG2 and decreased levels of FA2 glycan. The distribution of glycans on individual chains was also affected, with the &gamma, chain, responsible for physiological functions of fibrinogen (such as coagulation and platelet aggregation), being most prone to these alterations. Increased levels of multi-antennary N-glycans in ESRD-PD patients were also associated with the type of dialysis solutions, whereas an increase in the fucosylation levels was strongly related to the peritoneal membrane damage. Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.

Background and Aims To determine the concentration of Alpha-2-macroglobulin (α2M) and its activity in patients treated with peritoneal dialysis (PD) and healthy subjects (H). Method a cross-sectional study included 50 PD and 30 H, in which the concentration of active α2M molecules was determined. The measurement is based on covalent binding of α2M and trypsin and zymography with gelatin incorporated into the electrophoretic gel. Results The intensity of proteolytic bands seen with native α2M was analyzed in relation to the concentration of α2M in patients with PD with less and / or more than three peritonitis. Linear dependence was only visible in the case of the upper range, which originates from the intact α2M-trypsin complex. The highest coefficient of variation is calculated for the smallest α2M concentration (4.2%). The signal intensities originating from α2M (H) were higher compared to PD, with the PD group being lower in patients with higher peritonitis, and the difference was more pronounced as concentration increased, resulting in a lower slope of dependence. The proposed method can reliably measure the amount of α2M originating in a group H, while the quantification of α2M in PD groups that may have structurally altered α2M can be seen more for condition estimation than for accurate measurements. The zymographic test in this experiment allows us to investigate the relationship of the concentration, structure and function of α2M in different pathological conditions, as well as in the presence of modifying agents that can accompany them. Conclusion A simple method for the determination of α2M concentration and function by zymography has been developed, which can be used to examine residual α2M activity after partial denaturation or structural modification due to disease.

A characteristic tumor suppressor protein 53 (p53) mutational profile of genotoxic action of aristolochic acid was identified in the upper urothelial carcinoma (UUTT) associated with Balkan nephropathy (BEN). In the present study, we examined the prognostic value of tissue-based molecular markers in overall-survival (OS) risk after surgical treatment of UUTT, adjusted for gender, age and urological characteristics in 32 patients with BEN. Immunohistochemical examination of p53, the proliferation cell nuclear antigen (PCNA), the human epidermal growth factor receptor 2 (c-ErbB2; also known as HER-2/neu) proto-oncogene and the in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for apoptosis detection were used to examine serial tumor sections. The median OS-time was 60 months for UUTT operation; the mortality rate (18.7%) was related to (new) disease (re)occurrence or invasion in 12-216 months. High-grade (p=0.029), TUNEL>0.36%+ cells (p=0.010), and c-ErbB2+ cells (p=0.014) can define the risk of tumor invasion. Patients with Balkan nephropathy that develop UUTT at a stage greater than pT1 (with apoptosis TUNEL+ cells >0.36% and p53+ cells greater than 10%) were at high risk of poor-OS after the tumor surgery (h(x)=6.35; p=0.045). The obtained data present evidence for p53, cErbB2 and apoptosis deregulation, as a result of environmental toxin action. This is the first report of molecular biomarker linkage with OS for BEN-associated UUTT.