Factor X Deficiency Management for Elective Cesarean Delivery in a Pregnant Patient.

BACKGROUND Congenital factor X deficiency is a rare inherited coagulopathy. Pregnancies in women with this disorder are often associated with adverse outcomes, including miscarriage, premature labor, and hemorrhage during pregnancy and in the peripartum period. The literature on this disorder is sparse and shows a limited number of successful pregnancies in women with factor X deficiency. CASE REPORT In this report, we present the case of a successful pregnancy and term delivery by elective cesarean section in a 39-year-old primigravida with congenital factor X deficiency. Medical management followed the recommendations of an interdisciplinary team comprising specialists in obstetrics, anesthesia, transfusion medicine, hematology, and neonatology. This high-risk pregnancy was successfully brought to term, and a healthy male neonate was delivered by elective cesarean section at 39 weeks' gestation. The patient's factor X deficiency (0.19 kIU/L) was treated using 4 units of solvent-detergent-treated fresh frozen plasma (SD-FFP) 1 h before the cesarean section, leading to hemostatic levels of factor X and an uneventful intraoperative course. Postoperatively, the patient's factor X levels were controlled daily and corrected using SD-FFP as needed, with no clinically significant blood loss. CONCLUSIONS SD-FFP can be used to manage congenital factor X deficiency in the peripartum period and maintain perioperative blood loss within normal limits.

Are Croatian blood donors obese?

The rising prevalence of overweight and obesity is characterized as a pandemic of the modern era. The purpose of this study was to analyze the prevalence of overweight and obesity in healthy blood donors in Primorje-Gorski Kotar County, Croatia, and the relationship between socio-demographic factors, lifestyle and eating habits, and body mass index (BMI), including the association of these factors with overweight and obesity. This cross-sectional study included 1255 healthy individuals aged between 18 and 70 years who donated blood between January 2015 and October 2016 at the Clinical Institute of Transfusion Medicine. Each participant completed a questionnaire regarding weight, height, blood type, socio-demographic factors, health parameters, physical activity, alcohol consumption, and smoking habits. Overweight was defined as BMI of 25-29.9 kg/m2, and obesity as BMI ≥30 kg/m2. A logistic regression model was used on data assessment. BMI was normal in 33.6% of participants, whereas 44.1% were overweight and 21.8% were obese. Higher BMI was correlated with male sex (odds ratio [OR]=0.21), lower education level (OR=0.77) and unhealthy diet (OR=0.57), whereas lower BMI was correlated with lower age (OR=2.05) and unemployment (OR=1.85). To our knowledge, this is the first study to investigate the prevalence of BMI in a healthy Croatian population; our results confirmed the findings of studies conducted in other European countries. Our results highlighted the importance of improving education levels and raising awareness of healthy dietary habits in high-risk groups, i.e. men and older individuals with lower education levels.

Interleukin-17 and Toll-like Receptor 10 genetic polymorphisms and susceptibility to large joint osteoarthritis.

Primary osteoarthritis (OA) is the most common type of a joint disease. It has a polygenic risk inheritance pattern and affects older people. The etiology of this disease is not fully understood. The aim of this study was to investigate the associations between polymorphisms in pro-inflammatory interleukin-17 (IL17A and IL17F) and anti-inflammatory Toll-like Receptor 10 (TLR10) genes with the risk for development of advanced stage hip and knee primary OA in the Croatian population. A total of 500 OA patients and 597 controls were genotyped for IL17A SNP (rs2275913), IL17F SNPs (rs763780 and rs1889570), and TLR10 (rs11096957) genes. The allelic and genotypic frequencies of IL17F SNP (rs763780) showed statistically significant differences in comparisons of controls with hip-but not knee-OA patients. The major allele (T) of rs763780 was associated with the lower risk for developing hip OA (p = 7.9 × 10-4 , OR = 0.45, 95%CI = 0.27-0.74), whereas the minor allele (C) was associated with susceptibility to hip OA (p = 7.9 × 10-4 , OR = 2.24, 95%CI = 1.35-3.72). The genotype T/T was associated with the protection to hip OA (p = 3.9 × 10-4 , OR = 0.41, 95%CI = 0.24-0.70), and, lastly, the genotype T/C was associated with the higher risk to acquiring hip OA (p = 2.6 × 10-4 , OR = 2.50, 95%CI = 1.47-4.25). TLR10 SNP rs11096957 was found significantly associated with predisposition to hip OA (p = 0.04, OR = 1.41, 95%CI = 1.02-1.94) but not knee OA. Our findings suggest that hip OA in Croatian population might have a different genetic risk regarding the IL17 and TLR10 gene locus than knee OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1684-1693, 2018.

Complement-dependent cytotoxicity and Luminex technology for human leucocyte antigen antibody detection in kidney transplant candidates exposed to different sensitizing events.

BACKGROUND: The aim of this study was to determine the frequency of exposure to different sensitizing events (SEs) and to assess their effects on human leucocyte antigen (HLA) alloimmunization in transplant candidates using two different HLA antibody screening techniques: complement-dependent cytotoxicity (CDC) and Luminex. METHODS: This retrospective study included HLA antibody screening results for 163 patients on the kidney transplant waiting list (WL) tested from March 2012 until the end of December 2015 at the Tissue Typing Laboratory, Rijeka, Croatia. All sera samples were tested using the CDC and Luminex techniques in parallel. RESULTS: Two-thirds of the patients [114 (70%)] on the WL were exposed to transfusions, pregnancies and/or kidney transplant. The pre-transplant sera of 104 (63.80%) patients were negative for antibodies. In the sera of 23 (14.11%) patients, HLA antibodies were detected by CDC and Luminex and in the sera of 36 (22.09%) patients by Luminex only. CONCLUSION: In patients on kidney WL, previous organ transplantation represents the strongest immunogenic stimulus, followed by blood transfusions (the most frequent SE) and pregnancies. Although Luminex is more sensitive than CDC in HLA antibody detection, the decision on unacceptable HLA antigens in WL patients has to be based on the results of both assays and the patient's immunization history.

Endothelial dysfunction mediated by interleukin-18 in patients with ischemic heart disease undergoing coronary artery bypass grafting surgery.

When medication management or percutaneous coronary intervention is not successful in patients with advanced ischemic heart disease, surgical revascularisation-predominantly coronary artery bypass grafting (CABG)-is considered the gold standard. However, CABG surgery can lead to ischemia/reperfusion injury, which is characterized by a strong inflammatory response. Interleukin (IL)-18, is a strong inflammatory mediator, that is released from cardiomyocytes and can be found in the systemic circulation of patients during and immediately after CABG surgery. The existing damage of endothelial glycocalyx in patients with ischemic heart disease is further impaired concurrently during the surgery due to the anaesthesia-surgical technique used and intravascular fluid loading. This results in the increased incidence of adverse events, including myocardial infarction. IL-18 leads to the activation of lymphocyte cytotoxicity via cytotoxic mediators (Fas ligand, Tumour necrosis factor (TNF)-related apoptosis-inducing ligand, perforin, and granulysin). We hypothesize that IL-18 is released locally in the heart and the systemic circulation in patients undergoing CABG surgery and may be correlated with the level of activity of circulating lymphocytes. In turn, this may lead to lymphocyte-mediated cytotoxicity directed toward damaged and activated endothelial cells. Shear stress glycocalyx, as well as damaged and activated endothelial cells then become the main the source of pro-inflammatory cytokines, chemokines, and adhesion molecules. These attract activated lymphocytes to adhere to the endothelium or enter the subintimal layer, increasing existing or initiating the formation of new plaques, which leads to the development of myocardial infarction during or shortly after surgery. To evaluate our hypothesis, we will measure the local concentration of IL-18 in the sinus coronarius and systemic circulation. These values will then be correlated with immunological and biochemical parameters, predominantly with the concentration of degradation products of glycocalyx and cytotoxic mediators in activated lymphocytes. If our hypothesis is correct, measuring the IL-18 concentration that is responsible for glycocalyx deterioration, may become a useful tool for predicting myocardial infarction occurrence in patients undergoing CABG surgery.

Pretransplantation monitoring of HLA antibodies by complement dependent cytotoxicity and Luminex-based assays.

BACKGROUND: The introduction of more sensitive techniques, such as Luminex® for HLA antibody screening of patients awaiting organ transplantation has resulted in a better understanding of transplantation immunology and improvements in clinical practice. OBJECTIVE: The interpretation of the results obtained only by Luminex® can lead to inaccurate evaluation of a patient's antibody status and unjustified rejection of a potential organ donor. The aim of this study was to demonstrate the benefits of performing HLA antibody screening in the sera of patients on the waiting list for organ transplantation by two different assays, complement dependent cytotoxicity (CDC) and Luminex®. METHODS: A retrospective analysis was performed on 563 pretransplant serum samples from 141 patients on the kidney transplantation waiting list in Rijeka, tested from March 2012 until March 2015. All samples were tested in parallel by the CDC assay and the Luminex®-based assay. RESULTS: Out of the 563 samples tested 302 (53.7%) tested negative for HLA antibodies and 88 (15.6%) positive by both assays. From 173 (30.7%) samples with discordant results 149 (26.5%) were CDC negative and Luminex® positive, while 24 (4.3%) were CDC positive and Luminex® negative. Among the Luminex positive patients seven did not experience any immunizing events. CONCLUSION: Evaluation of the HLA antibody status in patients on a waiting list for organ transplantation should be based on the results of the both CDC and Luminex® (or other sensitive) assays in accordance to information about patient's clinical status and exposure to immunizing events.

Donor-specific antibodies require preactivated immune system to harm renal transplant.

BACKGROUND: It is an unresolved issue why some kidney transplant recipients with pretransplant donor-specific HLA antibodies (DSA) show a high transplant failure rate, whereas in other patients DSA do not harm the graft. We investigated whether help from preactivated T-cells might be necessary for DSA to exert a deleterious effect. METHODS: The impact of pretransplant DSA and immune activation marker soluble CD30 (sCD30) on 3-year graft survival was analyzed in 385 presensitized kidney transplant recipients. FINDINGS: A deleterious influence of pretransplant DSA on graft survival was evident only in patients who were positive for the immune activation marker sCD30. In the absence of sCD30 positivity, 3-year graft survival was virtually identical in patients with or without DSA (83.1±3.9% and 84.3±2.8%, P=0.81). A strikingly lower 3-year graft survival rate of 62.1±6.4% was observed in patients who were both sCD30 and DSA positive (HR 2.92, P<0.001). Even in the presence of strong DSA with ≥5000 MFI, the 3-year graft survival rate was high if the recipients were sCD30 negative. INTERPRETATION: Pretransplant DSA have a significantly deleterious impact on graft survival only in the presence of high pretransplant levels of the activation marker sCD30.

Connections between nutritional status and proton pump inhibitor therapy in patients scheduled for cardiovascular rehabilitation after treatment for ischaemic and valvular heart disease.

BACKGROUND: Multiple and yet uncertain connections exist between cardiovascular diseases and the nutritional status of patients, particularly in relation to cardiovascular treatments. Proton pump inhibitors (PPI) are among the most commonly used group of drugs. AIM: To analyse utilisation of PPI in association with nutritional risk of patients scheduled for rehabilitation after treatment for ischaemic and valvular heart disease. METHODS: Retrospective analyses on a consecutive sample of patients, which included drug utilisation of PPI and nutritional risk screening, using a standardised NRS-2002 tool. The patients (n = 536) were divided into groups based on previous cardiovascular treatments and use of PPI. RESULTS: Nearly half of the patients (244, 46.1%) had PPI in their chronic therapy despite the clinically negligible prevalence of conditions that are their fundamental indications. The odds for using PPI in patients with increased nutritional risk, estimated by logistic regression, were 3.34 (95% confidence intervals [CI] 2.26-4.94), p < 0.001. Receiver operating curve analyses also revealed significant differences of PPI utilisation in connection with NRS-2002 > 3: positive likelihood-ratio (LR) 2.35 (95% CI 2.10-2.60); negative LR 0.46 (95% CI 0.4-0.6); area under the curve (AUC) 0.720; p < 0.001; as well as the percentage weigh loss history > 6.36% (positive LR 2.22 [95% CI 2.00-2.50]; negative LR 0.41 [95% CI 0.30-0.50]; AUC 0.707; p < 0.001). CONCLUSIONS: Utilisation of PPI was found to be of relatively high prevalence and significantly associated with parameters of nutritional risk screening. Furthermore, it was in correlation with the age of patients and the existence of chronic kidney disease, which are well-established predispositions for poor nutritional status. Nutritional risk seems to be additionally negatively challenged by utilisation of PPI due to gastric malabsorption and anaemia.

Association of the FAM46A gene VNTRs and BAG6 rs3117582 SNP with non small cell lung cancer (NSCLC) in Croatian and Norwegian populations.

We analyzed for associations between a variable number of tandem repeat (VNTR) polymorphism in the Family with sequence similarity 46, member A (FAM46A) gene and a single nucleotide polymorphism (rs3117582) in the BCL2-Associated Athanogene 6 (BAG6) with non small cell lung cancer in Croatian and Norwegian subjects. A total of 503 (262 Croatian and 241Norwegian) non small cell lung cancer patients and 897 controls (568 Croatian and 329 Norwegian) were analyzed. We found that the frequency of allele b (three VNTR repeats) of FAM46A gene was significantly increased in the patients compared to the healthy controls in the Croatian and the combined Croatian and Norwegian subjects. Genotype frequencies of cd (four and five VNTR repeats) and cc (four VNTR repeats homozygote) of the FAM46A gene were significantly decreased in the patients compared to the healthy controls in the Croatian and Norwegian subjects, respectively. Logistic regression analyses revealed FAM46A genotype cc to be an independent predictive factor for non small cell lung cancer risk in the Norwegian subjects after adjustment for age, gender and smoking status. This is the first study to suggest an association between the FAM46A gene VNTR polymorphisms and non small cell lung cancer. We found also that BAG6 rs3117582 SNP was associated with non small cell lung cancer in the Norwegian subjects and the combined Croatian-Norwegian subjects corroborating the earlier finding that BAG6 rs3117582 SNP was associated with lung cancer in Europeans. Logistic regression analyses revealed that genotypes and alleles of BAG6 were independent predictive factor for non small cell lung cancer risk in the Norwegian and combined Croatian-Norwegian subjects, after adjustment for age and gender.

Association of Kidney Graft Loss With De Novo Produced Donor-Specific and Non-Donor-Specific HLA Antibodies Detected by Single Antigen Testing.

BACKGROUND: The association of donor-specific HLA antibodies (DSA) with kidney graft failure has been addressed previously; however, the majority of studies were based on small numbers of patients with graft failure. METHODS: We investigated 83 patients with failed kidney transplants for a possible association of de novo development and persistence or loss of pre-existing DSA with graft failure. Single Antigen Bead assay-detected DSA and non-DSA antibodies were compared between patients with graft loss and matched controls with functioning grafts. RESULTS: The incidence of weak de novo DSA or non-DSA at a mean fluorescence intensity of 500 or higher was higher in the graft loss than in the nonrejector group (76% vs 40%, P < 0.001). Because of the low number of patients developing de novo DSA, the DSA results did not reach statistical significance (only 22% of patients with graft loss developed de novo DSA). However, at all cutoffs, there was a significantly higher rate of graft loss in patients with de novo non-DSA. The incidence of strong pretransplant DSA that persist after transplantation was higher in the graft loss group (10% vs 1%, P = 0.034). When C1q-binding ability in sera of rejectors and nonrejectors with posttransplant de novo or persistent DSA was compared, none of the nonrejectors demonstrated C1q positivity, whereas 43% of patients with graft loss showed C1q-positive antibodies, although not necessarily donor-specific (P < 0.001). CONCLUSIONS: Our data show that the posttransplant presence of persisting or de novo HLA antibodies, especially if C1q binding, is associated with graft loss, even if the antibodies are not specific for mismatched donor HLA.

Susceptibility to large-joint osteoarthritis (hip and knee) is associated with BAG6 rs3117582 SNP and the VNTR polymorphism in the second exon of the FAM46A gene on chromosome 6.

Family with sequence similarity 46, member A (FAM46A) gene VNTR and BCL2-Associated Athanogene 6 (BAG6) gene rs3117582 polymorphisms were genotyped in a case-control study with 474 large-joint (hip and knee) osteoarthritis (OA) patients and 568 controls in Croatian population by candidate-gene approach for association with OA. We found that BAG6 rs3117582 SNP genotypes were associated with protection (major allele homozygote) and susceptibility (major-minor allele heterozygote) to OA. BAG6 rs3117582 major allele (A) was associated with reduced risk to OA while the minor allele (C) was associated with increased risk to OA. We identified 6 alleles harboring 2 to 7 repeats making 20 genotypes for FAM46A. A rare FAM46A VNTR genotype comprising VNTR alleles with four and seven repeats (c/f) was associated with increased OA risk in both genders. The genotype with four and six repeats (c/e) was also associated with increased risk to OA in males. A polymorphic FAM46A allele with six repeats (e) was associated with reduced risk to OA in females. Our results suggest association between the FAM46A gene, BAG6 gene and OA in Croatian population, respectively. This is the first study to show associations between these genetic loci and OA.

Association of variable number of tandem repeats in the coding region of the FAM46A gene, FAM46A rs11040 SNP and BAG6 rs3117582 SNP with susceptibility to tuberculosis.

We analyzed for association between the Family with sequence similarity 46, member A (FAM46A) gene (located on chromosome 6q14.1), BCL2-Associated Athanogene 6 (BAG6) gene (located on chromosome 6p21.3) and tuberculosis in Croatian Caucasian. We genotyped the FAM46A rs11040 SNP, FAM46A VNTR and BAG6 rs3117582 polymorphisms in a case-control study with 257 tuberculosis patients and 493 healthy individuals in a Croatian Caucasian population. We found that genotype FAM46A 3/3 (three VNTR repeats homozygote) was associated with susceptibility to tuberculosis (p<0.0015, Pcorr.<0.029, Odds ratio = 2.42, 95% Confidence Interval = 1.34-4.3). This association suggests that the protein domain encoded by the VNTR might be important for the function of the FAM46A protein, which, in turn, could be relevant in developing tuberculosis. In addition, we found that FAM46A rs11040 SNP:FAM46A VNTR:BAG6 haplotype 132 (G-3-C) is associated with susceptibility to tuberculosis (p<0.012, pcorr.<0.024, Odds ratio 3.45, 95% Confidence Interval = 1.26-9.74). This may suggests that the interaction between the FAM46A and BAG6 proteins may be involved in tuberculosis etiology. We found also that infection of human macrophages with heat-killed M. tuberculosis (H37Rv) led to over-expression of FAM46A (VNTR 3/4) transcript. This is the first study to show associations between the FAM46A gene VNTR polymorphisms, FAM46A rs11040 SNP:FAM46A VNTR:BAG6 haplotypes and any disease.

IL1B -511(G>A) and IL1RN (VNTR) allelic polymorphisms and susceptibility to knee osteoarthritis in Croatian population.

Osteoarthritis (OA) is a frequent, destructive joint disease, with debilitating impact on a society regarding medical, social, and economic issues. Although causes of primary OA were still not fully elucidated, evidence points to complex genetic risk that varies among different population groups, including the interleukin-1 (IL-1) gene cluster. Here, we sought to determine allelic and genotypic frequencies of the IL-1ß (IL1B) and the IL-1 receptor antagonist (IL1RN) genes using single nucleotide polymorphism (SNP) at -511(G>A; rs16944) and the variable number tandem repeat (VNTR) in a case-control study with 238 patients that have undergone total or partial knee replacement and 495 healthy blood donors as controls in Croatia. The alleles of the IL1B gene at -511G>A were detected by Taqman real-time polymerase chain reaction (PCR) method and IL1RN VNTR by amplifying its DNA by PCR. The genotypes 1-2/1-2 and 2-1/2-2 at IL1B G -511A-IL1RN (VNTR) showed trends for association with the occurrence of the knee OA in this population (P = 0.09; P = 0.07, respectively). Furthermore, neither the alleles nor the haplotypes were found associated with the predisposition to knee OA. Our findings suggest that knee OA might have a different genetic risk in this Caucasian population. We did not found significant association of the IL1 gene cluster (IL1B-IL1RN) with severe knee OA. However, we found that two genotypes (1-2/1-2 and 2-1/2-2) show a trend toward association with susceptibility to disease.

Helicobacter pylori infection and acute myocardial infarction.

The aim of this investigation was to determine whether H. pylori infection is an independent risk factor for acute myocardial infarction (AMI), determine is there a link between H. pylori infection and severity of disease. In this prospective, single centre study, were enrolled 100 patients with AMI and control group was consisted 93 healthy individuals. The results of this study showed no difference between H. pylori seropositivity distribution in the investigate and control group (29 vs. 26 %) and there was no significant difference on the severity of the disease. There was significant association in the patients with three and more risk factors, where the patients with lower blood pressure (124.4/77.4 vs. 145.9/87.7 mmHg) and better controlled diabetes (HbA1c 6.1% vs. 6.9%) had greater risk for AMI if they are H. pylori seropositive. The large multicentric trials would be needed to define a precise role of H. pylori infection on the developement of AMI.

Hip osteoarthritis susceptibility is associated with IL1B -511(G>A) and IL1 RN (VNTR) genotypic polymorphisms in Croatian Caucasian population.

Among the predisposing factors to osteoarthritis (OA), a frequent destructive joint disease, is the complex genetic heritage including the interleukin-1 family members like the IL1ß (IL1B) and the IL1 receptor antagonist (IL1RN) genes. The aim of this study was to investigate allelic and genotypic frequencies of the IL1B gene single nucleotide polymorphism (SNP) at -511(G>A) and the variable number tandem repeat (VNTR) in the IL1RN gene in a Croatian Caucasian population of hip OA (HOA) cases and healthy controls. A total of 259 HOA patients with total hip replacement (THR) and 518 healthy blood donors as controls were genotyped for IL1B gene SNP -511(G>A) and the VNTR in the IL1RN gene associated with HOA. The genotype G/A (1/2) at IL1B was significantly associated with the protection of the HOA (p < 0.036, OR = 0.72, 95% CI = 0.52-0.99). The genotype G/G (1/1) had only a trend towards the susceptibility (p = 0.053, OR = 1.35, 95% CI = 0.98-1.86) to disease. None of the haplotypes IL1B -511(G>A) and IL1RN (VNTR) were found associated with the HOA. The haplotype 1-2 at these loci had only a trend to susceptibility (p = 0.065). Haplotype 1-3 had a significant male bias in diseased. Furthermore, genotype comprising 2-1/2-2 haplotypes was found significantly associated with predisposition to HOA (p = 0.027, OR = 2.23, 95% CI = 1.03-4.88), whereas genotype 1-1/2-2 with protection to disease (p = 0.028, OR = 0.65, 95% CI = 0.43-0.97). Our findings suggest that HOA in Croatian population might have a different genetic risk regarding the IL1 locus than has been reported for other Caucasian populations previously.

Perforin expression after acute myocardial infarction--a pilot study.

Perforin is an important mediator of inflammatory reactions. It is a quick-action cytotoxic mediator accumulated in the cytoplasmic granules of effector immunity cells (T lymphocytes, NK and NKT cells) which provide death signal in infected or transformed cells. Perforin-positive cells were previously detected in myocardial tissue during Trypanosoma cruzi infection and viral myocarditis while its role in chronic and progressive cardiovascular inflammatory disease such as atherosclerosis is almost completely unexplored. The perforin activity is also untested during acute coronary events that represent unexpected atherosclerotic complications due to the inflammatory destabilisation and atherosclerotic plaque rupture. The aim of this study was to investigate the presence of perforin, an important immunological inflammatory molecule in peripheral blood lymphocytes during the early period after acute myocardial infarction. We analyzed three subject groups: women with ST-segment elevation acute myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI), conservatively treated women with acute myocardial infarction without ST-segment elevation (NSTEMI) and a control group of healthy volunteers. The STEMI and NSTEMI groups did not basically differ in medication neither in levels of routine laboratory tests, while troponin I were significantly higher in the STEMI group. In the study, we detected an early decrease of perforin-positive lymphocytes in STEMI patients that were in contrast with their persisting elevation among NSTEMI patients. Despite greater myocardial necrosis in the STEMI group, results of this pilot-study indicated the prolonged perforin-mediated inflammatory response in patients with NSTEMI. This perforin down-regulation that follows the coronary interventional reperfusion in STEMI emphasized the possible anti-inflammatory role of primary PCI among patients with acute myocardial infarction. Given that the issue of routine primary PCI in NSTEMI is nowadays highly topical, the results we expect in the wake of this pilot study could demonstrate a significant impact on clinical practice. Further research is needed to confirm these results, compare the perforin-mediated activity to other inflammatory mediators in acute coronary events and to examine their impact on the long-term outcome.

Evaluation of fresh frozen plasma usage at the University Hospital Center Rijeka.

The aim of this investigation was to assess the rate and appropriate use of fresh frozen plasma (FFP) at the Clinical Hospital Center Rijeka in two six-month periods, at an interval of 5 years, before and after introducing clinical standards for transfusion practice and hemovigilance, and to evaluate the results of applied measures. We studied 315 patients transfused with 1341 doses of FFP in two six-month periods from September to February of 1999/2000 and 2004/2005. The first period (1999/00) of the study was retrospective and 226 patients were transfused with 928 FFP units. The second period (2004/05) was prospective and we studied 89 patients transfused with 413 units. In the first period blood bank records were retrospectively reviewed and in the second period all FFP requests, performed coagulation tests and transfusion episodes were prospectively analyzed. The number of inappropriate transfusions decreased from 39.8% to 23.6%. In most patients (85.1%), coagulation tests were made prior to FFP transfusion. The number of patients transfused with one and two FFP doses decreased, while those transfused with three or more doses increased. Most of the appropriately transfused patients were those with active bleeding due to coagulation factor deficiency and massive transfusions. The least were those requiring reversal of warfarin effect. Our results demonstrated a decrease in the number of patients treated with FFP in the second period. The introduction of clinical standards of good transfusion practice and hemovigilance showed positive effects. Considering that there was a number of inappropriately transfused patients continued education of all health personnel engaged in transfusion treatment is evidently necessary.

Examining the presence of ABO(H) antigens of blood types in the saliva of patients with oral cancer.

Number of researches dealing with the influence of the ABO blood group antigens on the development of the oral cancer have hypothesized that people who do not secrete these substances in the saliva are more prone to suffer from this disease. The objective of this research is to examine this hypothesis. In total 114 subjects were examined, half of which suffered from oral cancer, while the other half was the healthy control group. All examinees were subjected to clinical examinations and the experimental group to pathohistological examination. An analysis of the secretor status was carried out using the Wiener agglutination test. The experimental group consisted of 78.95% of secretors, while the control group consisted of 82.46% of secretors. This difference is not statistically significant. The starting hypothesis that non-secretors are more prone to the development of oral cancer was not confirmed.

Association of CYP2C9 gene polymorphism with bleeding as a complication of warfarin therapy.

The aim of this study was to determine the association of bleeding as a complication of warfarin therapy with polymorphism of CYP2C9 gene (alleles 1, 2 and 3). The CYP2C9 is the main enzyme for warfarin metabolism. Study included 181 patients receiving warfarin for at least one month. Allele 1 of CYP2C9 gene (in 94.5%) and genotype *1/*1 (57.5%) prevailed. Allele 3 was found in 12.7% patients. Bleeding side-effects occurred in 18 patients (10%). Patients with allele *1 needed significantly higher maintenance warfarin dose (p=0.011). Those with allele *3 had significantly lower maintenance warfarin dose (p=0.005) and higher prothrombin time (PT) at induction (p=0.034). Bleeding occurred significantly more often in those with lower maintenance warfarin dose (p=0.017). Patients with allele *3 had increased risk of bleeding, with marginal significance (p=0.05). Polymorphism of CYP2C9 could determine dose of warfarin therapy and thus it could be related to the risk of bleeding complications. Allele *3 carriers need lower warfarin dose. Therefore, initially reduced warfarin induction dose in allele *3 carriers could avoid more prolonged PT and decrease the risk of bleeding complication.

Anti-inflammatory effects of exercise training in the early period after myocardial infarction.

The aim of this investigation was to determine the effect of exercise training on the levels of plasma cytokines and acute phase reactants in the early post acute myocardial infarction (AMI) period. Sixty patients were enrolled into this three-week cardiac rehabilitation study. The mean time from AMI was 7.08 +/- 1.60 days, and the patient mean age was 60 +/- 10 years. Subjects were randomly assigned to one of the two groups: the control group treated with standard measures, and the group with additional regular moderate-intensity exercise training. Physical activity was based on the ergospirometry test results. Apart from clinical follow-up and routine laboratory analysis we determined the levels of plasma cytokines: tumor necrosis factor (TNF-alpha), soluble TNF-alpha receptor 1 (TNF-alphaSR1), interleukin (IL)-8, IL-10, and acute phase reactants: high sensitivity C-reactive protein (hsCRP) and fibrinogen. The obtained results confirmed the hypothesis that the early post AMI period is an inflammatory state the intensity of which gradually decreases with standard treatment during the first month after AMI, while including patients into early exercise training improves their inflammatory profile by decreasing the level of acute phase reactant and TNF-alphaSR1.