•High concentrations of TNF-α superfamily members point to prompt activation of B cells in sepsis.•APRIL, BAFF and sTACI are good predictors of septic shock and lethal outcome in sepsis.•Their ...concentrations correlate well with SOFA, but do not correlate with PCT.•Lower BAFF and higher sTACI concentrations suggest increased apoptosis of B cells in septic shock.•sTACI is an anti-inflamatory cytokine that had the highest AUC in outcome prediction.
Members of TNFα superfamily, A proliferation inducing ligand (APRIL), B-cell activating factor (BAFF) and Transmembrane activator and calcium cyclophylin interactor (TACI) are main regulators of B-cell function. The aim of this study was to evaluate concentrations of APRIL, BAFF and soluble TACI (sTACI) receptor in septic patients compared to healthy controls and compare concentrations of these biomarkers depending on sepsis severity and outcome.
A total of 115 septic patients and 30 healthy volunteers were included and concentrations of APRIL, BAFF and sTACI were determined in all subjects at the admission (ELISA R&D Systems tests). Concentrations of these biomarkers in function of sepsis severity (sepsis n = 94 and septic shock n = 21) and outcome (lethal n = 40, recovery n = 75) were tested, as well as correlations with APACHE II and SOFA scores, immunoglobulins, complement, PCT and CRP concentrations.
Concentrations of all three biomarkers were significantly increased in septic patients compared to controls (AUCAPRIL = 0.982, AUCBAFF = 0.873, AUCsTACI = 0.683). Higher concentrations of APRIL and sTACI (p = 0.033, p = 0.037), and lower concentrations of BAFF (p = 0.005) were observed in patients with septic shock compared to sepsis. BAFF concentrations correlated positively with IgM, C3 and C4 levels. sTACI and APRIL were shown to be predictors of lethal outcome (p = 0.003, p = 0.049).
Concentrations of observedTNFα superfamily members are significantly increased in septic patients, confirming their role in sepsis pathogenesis.Higher concentrations of anti-inflammatory sTACI receptor correlated with severity of sepsis and poorer prognosis, thus potentially indicating domination of anti-inflammatory response in septic patients with worse outcome.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•Upgraded fractional model is presented for pharmacokinetics of methotrexate in children with leukaemia.•New parameter determination procedure is introduced.•Our fractional model can recognize all ...elimination patterns.•Our fractional model better fits observed non-monotonic behavior.
The aim of this study is to promote a model based on the fractional differential calculus related to the pharmacokinetic individualization of high dose methotrexate treatment in children with acute lymphoblastic leukaemia, especially in high risk patients.
We applied two-compartment fractional model on 8 selected cases with the largest number (4–19) of measured concentrations, among 43 pediatric patients received 24-h methotrexate 2–5g/m2 infusions. The plasma concentrations were determined by fluorescence polarization immunoassay. Our mathematical procedure, designed by combining Post’s and Newton’s method, was coded in Mathematica 8.0 and performed on Fujicu Celsius M470-2 PC.
Experimental data show that most of the measured values of methotrexate were in decreasing order. However, in certain treatments local maximums were detected. On the other hand, integer order compartmental models do not give values which fit well with the observed data. By the use of our model, we obtained better results, since it gives more accurate behavior of the transmission, as well as the local maximums which were recognized in methotrexate monitoring. It follows from our method that an additional test with a small methotrexate dose can be suggested for the fractional system parameter identification and the prediction of a possible pattern with a full dose in the case of high risk patients.
A special feature of the fractional model is that it can also recognize and better fit an observed non-monotonic behavior. A new parameter determination procedure can be successfully used.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Chronic kidney disease (CKD) is a serious illness with important consequences for patients and health systems. Estimation of prevalence and incidence, especially in early stages, is difficult due to ...a lack of epidemiological studies and consolidated registries. In general, the disease awareness is low, and thus CKD is not timely diagnosed in most cases. Robust screening programs are not implemented in Eastern European countries. A panel consisting of Primary Care Physicians and Nephrologists from Bulgaria, Croatia, Serbia, and Slovenia virtually met in December 2021 to discuss current CKD awareness and diagnostic approaches in the Balkan area The meeting resulted in specific calls to action in the region to improve the number and quality of epidemiology studies and the level of awareness among patients and medical communities, as well as implementation of screening programs in high-risk populations. Collaboration between specialists was acknowledged as a crucial driver for optimal management of patients with CKD. Joint efforts are required to persuade healthcare authorities to establish specific policies for better care of kidney patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Introduction/Objective. Fabry disease (FD) is an X-linked lysosomal storage disease that develops as a consequence of mutation in the alpha-galactosidase A (GLA) gene. There are more than 1080 known ...variants in the GLA gene. Some of them are pathogenic, but most of them are benign or represent the genetic change that can be classified as a genetic variant of unknown significance or simply be a representation of genetic polymorphism. There are two main features of FD, classic form and late-onset variants of disease. The main target organs in patients with FD are the kidneys, heart, and nervous system. Bearing in mind the fact that FD is a rare disease, the best way for active searching of patients is high-risk population screening, after which family screening for every proband case should be performed. Methods. In this paper, we present results of a multicentric pilot study that represents findings from the screening of hemodialysis patients for FD in six hemodialysis units in Vojvodina. Results. We have found one patient with benign mutation and 16 patients with genetic polymorphisms in GLA gene. We have learned that genetic changes in GLA gene can be frequent, but very rarely are of clinical significance and lead to manifestations of FD. Conclusion. Results of this screening study will give us important insights into our future work.
Introduction. A single pass albumin dialysis (SPAD) is a form of extracorporeal liver support system for removing albumin-bound toxins and water-soluble substances that accumulate in liver failure ...(LF). Case report. We presented three patients hospitalized for LF and treated using the SPAD at the University Clinical Center of Vojvodina, Serbia, from 2018 to 2019. Two of the patients presented with acute LF and one with acute-on-chronic LF. A total of 6 SPAD sessions were performed on each patient, resulting in decreased serum bilirubin and bile acid levels and hepatic encephalopathy grade. On discharge from the hospital, the liver function was improved in all the patients. Conclusion. SPAD removes the hepatotoxic substances without improvement of synthetic liver function. It represents a supportive treatment for LF patients who do not respond to the standard of care, offering a longer time for bridging to organ transplantation or spontaneous recovery of the liver function.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background/Aim. Catheter-related infections are a significant morbidity and mortality cause in patients on hemodialysis. The objective of this study was to determine the incidence, to analyze risk ...factors and to identify etiological causes of catheter-related infections in these patients. Methods. The study was carried out at the Clinic for Nephrology and Clinical Immunology of the Clinical Centre of Vojvodina, from August, 2012 to May, 2015. One hundred and thirteen patients on chronic hemodialysis participated in the study. The risk factors of catheterrelated infections in the infected patients were to those in the control group, as follows: demographic and laboratory parameters, co-morbidities and the use of immunosuppressive therapy, the length of hemodialysis treatment, urgent catheter placement, the position and placement difficulties, the number of insertions and catheter maneuvering, the existence of permanent vascular access in maturation or without a vascular access in the course of catheter positioning, catheter life, surgical procedures (? 30 days from catheter placing), the length of hospitalization and isolated infection causes. Results. One hundred and ninety-seven catheters were placed in 113 patients, among which 182 of them temporary. The total number of catheter days was 17.842, the incidence of infections was 3.53/1,000 catheter days. During the monitoring period, 63 catheter-related infections were diagnosed, 54 (85.7%) with temporary and 9 (14.3%) with permanent catheters. Multivariate logistic regression analysis (with border values/ levels determined by receiver operating characteristic ? ROC analysis) determined independent predictors of catheter-related infections in the following order: hemoglobin levels < 95 g/l (p < 0.001) and albumin levels < 33 g/l (p = 0.041), catheter duration of > 90 days (p = 0.004), > 2/day catheter maneuvering (p = 0.011) and the duration of hospitalization of > 15 days (p = 0.003). The main pathogen was Staphylococcus spp. Coagulase negative. Conclusion. Intensifying of prevention measures and infection control would significantly reduce the frequency of catheter-related infections and the number of hospitalizations. The timely creation of a native arteriovenous fistula would decrease the use of hemodialysis catheters.
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Introduction. Post-transplant lymphoproliferative disorder (PTLD) is one of the most severe and often fatal complications observed after solid organ and bone marrow transplantations. Case outline. We ...present a case of a patient born in 1989 who underwent a living related donor renal transplantation at the age of 16. Induction therapy implied the administration of anti-thymocyte globulin and corticosteroids, and maintenance therapy encompassed a combination of three immunosuppressive agents ? tacrolimus, mycophenolate mofetil, and corticosteroid. The patient experienced first complications six months after transplantation, manifested as aggravation of tonsillitis symptoms and subsequent dysphagia. Histopathological and immunohistochemical finding of tonsillectomy specimens suggested polymorphic PTLD (with high expression of Epstein?Barr virus latent membrane protein antigen). Definitive diagnosis of diffuse large B-cell lymphoma (CD20+) was established upon analysis of oesophageal bioptate. Antiviral therapy was applied, along with rituximab and a combination of cyclophosphamide, doxorubicin (hydroxydaunomycin), vincristine, and prednisolone (CHOP therapy), whilst the dosage of basic immunosuppressive drugs was reduced. Complex diagnostic procedures confirmed the absence of disease recurrence and stable graft function five years after completing the PTLD therapy. Conclusion. The presented case of our patient, who developed PTLD after renal transplantation, demonstrated that appropriate early diagnosis, reduction of immunosuppressive regimens, and vigilant application of immunomodulatory and chemotherapy could result in complete disease remission, yet preserving and maintaining the stable function of the transplant.
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Suboptimal correction of anemia is associated with increased prevalence of cardiovascular diseases and increased morbidity and mortality of pre-dialysis and dialysis patients. The aim of the study ...was to compare the effect of optimal vs. suboptimal correction of anemia in hemodialysis patients with left ventricular hypertrophy.
The study included 50 patients, 32 males and 18 females, their mean age being 49.4±11.8 years, from five hemodialysis centers (Clinical Hospital Center Zvezdara, Beograd, Clinical Center Novi Sad, hospitals in Krusevac, Pirot and Zrenjanin). The patients had suboptimal hemoglobin level in spite of therapy (7.8±3.8 g/dl). In addition, the most important inclusion criteria was the left ventricular mass index above 160 g/m2 and the primary efficacy parameter was a decrease in the left ventricular mass index during 12 month study period.
During the study, the number of patients who reached their hemoglobin >12 g/dl increased and the target hemoglobin (12-13 g/dl) was achieved in 24 (52%) of patients at the end of the study. At the same time, the left ventricular mass index significantly decreased as compared with the initial values (p=0.014). The left ventricular mass index was not significantly decreased in the patients who did not achieve the target hemoglobin level (207±65 vs. 217±38 g, p=ns) as compared with the patients who achieved the target hemoglobin (179±32 g/ m2 vs. 197±38 g/m2, p=0.007). The left ventricular ejection fraction did not change significantly during the study period.
Anemia correction with erythropoietin β resulted in the significantly corrected left ventricular hypertrophy in hemodialysis patients who had had a suboptimal hemoglobin level. Our results have shown that correction of left ventricular hypertrophy
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The aims of the study were to determine the percentage of patients on regular hemodialysis (HD) in Serbia failing to meet KDOQI guidelines targets and find out factors associated with the risk of ...time to death and the association between guidelines adherence and patient outcome.
A cohort of 2153 patients on regular HD in 24 centers (55.7% of overall HD population) in Serbia were followed from January 2010 to December 2012. The percentage of patients failing to meet KDOQI guidelines targets of dialysis dose (Kt/V>1.2), hemoglobin (>110g/L), serum phosphorus (1.1–1.8mmol/L), calcium (2.1–2.4mmol/L) and iPTH (150–300pg/mL) was determined. Cox proportional hazards analysis was used to select variables significantly associated with the risk of time to death.
The patients were on regular HD for 5.3±5.3 years, dialyzed 11.8±1.9h/week. Kt/V<1.2 had 42.4% of patients, hemoglobin <110g/L had 66.1%, s-phosphorus <1.1mmol/L had 21.7% and >1.8mmol/L 28.6%, s-calcium <2.1mmol/L had 11.7% and >2.4mmol/L 25.3%, iPTH <150pg/mL had 40% and >300pg/mL 39.7% of patients. Using Cox model (adjustment for patient age, gender, duration of HD treatment) age, duration of HD treatment, hemoglobin, iPTH and diabetic nephropathy were selected as significant independent predictors of time to death. When targets of five examined parameters were included in Cox model, target for KtV, hemoglobin and iPTH were found to be significant independent predictors of time to death.
Substantial proportion of patients examined failed to meet KDOQI guidelines targets. The relative risk of time to death was associated with being outside the targets for Kt/V, hemoglobin and iPTH.
Los objetivos del estudio fueron determinar el porcentaje de pacientes en tratamiento de hemodiálisis (HD) regular de Serbia en los que no se alcanzaron los objetivos de la guía KDOQI y determinar los factores asociados al riesgo de tiempo hasta la muerte, así como la asociación entre el cumplimiento de la guía y los resultados clínicos.
Se llevó a cabo un seguimiento de una cohorte de 2153 pacientes en HD regular de 24 centros de Serbia (un 55,7% de la población total en HD) entre enero de 2010 y diciembre de 2012. Se determinó el porcentaje de pacientes que no alcanzaron los objetivos establecidos en la guía KDOQI respecto a dosis de diálisis (Kt/V>1,2), hemoglobina (>110 g/L), fósforo en suero (1,1-1,8 mmol/L), calcio (2,1-2,4 mmol/L) e iPTH (150-300 pg/mL). Se utilizó un modelo de riesgos proporcionales de Cox para identificar las variables con una asociación significativa con el riesgo de tiempo hasta la muerte.
Los pacientes habían estado en HD regular durante un periodo de 5,3±5,3 años, con un tiempo de diálisis de 11,8±1,9 horas/semana. Se observaron valores de Kt/V <1,2 en el 42,4% de los pacientes, hemoglobina <110 g/L en el 66,1%, fósforo en suero <1,1 mmol/L en el 21,7% y >1,8 mmol/L en el 28,6%, calcio en suero <2,1 mmol/l en el 11,7% y >2,4 mmol/L en el 25,3%, iPTH <150 pg/mL en el 40% y >300 pg/mL en el 39,7%. Con el empleo de un modelo de Cox (con ajuste respecto a edad del paciente, sexo y duración del tratamiento de HD) se seleccionaron las variables de edad, duración del tratamiento de HD, hemoglobina, iPTH y nefropatía diabética como factores predictivos independientes significativos del tiempo hasta la muerte. Al introducir los objetivos de los cinco parámetros examinados en un modelo de Cox, se observó que los objetivos de KtV, hemoglobina e iPTH eran factores predictivos independientes para el tiempo hasta la muerte.
Una parte sustancial de los pacientes examinados no alcanzaron los objetivos establecidos en la guía KDOQI. El riesgo relativo del tiempo hasta la muerte se asoció al hecho de no estar en el objetivo de Kt/V, hemoglobina e iPTH.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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