The Prognostic Role of CYP Enzyme in Kidney Transplantation: A Single Centre Experience.

BACKGROUND: The main goal of immunosuppressive agents is to reach a balance of preserving allograft function while minimizing adverse effects. The purpose of our research is to corroborate the role of CYP3A enzyme in developing individual medication therapy via measuring medicine levels in patients' blood samples. METHODS: This retrospective analysis studies 15 kidney transplant recipients. We carried out genotyping (CYP3A5, CYP3A4) after isolating DNA and RNA in patient and donor blood samples; we also determined CYP3A4 messenger RNA expression in case of recipients. Tacrolimus blood levels, dosage, and tacrolimus concentration normalized by dose and the body weight (C0/D ratio) were evaluated. RESULTS: In this research, recipients were divided into 2 groups based on their CYP3A5 genotype. Those who carry CYP3A5*1 allele (*1/*1 or *1/*3) are CYP3A5 expressors, whereas those who are homozygous for the nonfunctional CYP3A5*3 allele are CYP3A5 nonexpressors. There were 3 patients with functioning CYP3A5 enzyme (patients with CYP3A5*1/*3 genotype) where increased tacrolimus metabolism was expected. Our data show that C0/D ratio of CYP3A5 nonexpressors was around 3 times higher than of CYP3A5 expressors. Looking at CYP3A4 enzyme, we found 1 patient carried CYP3A4*22/*22 genotype where we expected decreased CYP3A4 expression. It is clear that this patient had adequate therapy medication levels (9.50 µg/L) despite having received very low dosage of tacrolimus (0.03 mg/weight/d). CONCLUSIONS: Our results confirmed the importance of determining CYP status of recipients after a transplant because individual differences were observed in tacrolimus treatment that were partly influenced by CYP status of recipients.

Depression and Anxiety Symptoms Are Associated with Mean Platelet Volume in Autoimmune Disorders.

Platelets are increasingly considered a bridge between mental and immunological disorders. However, data relating to platelet parameters in patients with autoimmune disorders are limited. The aim of the present study was to investigate, for the first time, the association of platelet parameters with the symptoms of affective disorders in patients with autoimmune conditions. In this cross-sectional study, we measured the complete blood count (CBC), the Generalized Anxiety Disorder Scale for anxiety (GAD-7), and the Beck Depression Inventory for depression (BDI) in 121 patients with autoimmune disorders. Mean platelet volume (MPV) was positively correlated with both anxiety and depression. Platelet distribution width (PDW) was negatively correlated with anxiety and depression. Before adjustment for covariates, logistic regression analysis revealed a significant association of MPV with depression and anxiety. After adjustment for covariates, only depression was associated with MPV. The area under the ROC curve of MPV for GAD-7 determined anxiety and BDI determined depression was 0.63. Our study showed that among the CBC hematological parameters, the MPV might be a useful biomarker of depression and anxiety in patients with autoimmune disorders. Further investigations of platelet parameters in controlled prospective studies are warranted to confirm our preliminary results.

Platelet count and mean volume in acute stroke: a systematic review and meta-analysis.

Changes of mean platelet volume (MPV) and platelet count (PC) could be a marker or a predictor of acute stroke (AS). We conducted a systematic review and meta-analysis of the published literature on the reporting of MPV and PC in AS. Studies were included in accordance with Patient Population or Problem, Intervention, Comparison, Outcomes, and Setting framework. The PRISMA strategy was used to report findings. Risk of bias was assessed with the Newcastle-Ottawa Scale. We included 34 eligible articles retrieved from the literature. PC was significantly lower in AS patients [standardized mean difference (SMD) = - 0.30, (95% CI: - 0.49 to - 0.11), N = 2492, P = .002] compared with controls (N = 3615). The MPV was significantly higher [SMD = 0.52 (95% CI: 0.28-0.76), N = 2739, P < .001] compared with controls (N = 3810). Subgroup analyses showed significantly lower PC in both ischemic stroke (Difference SMD = -0.18, 95% CI: -0.35-0.01) and hemorrhagic stroke (-0.94, -1.62 to -0.25), but only samples by citrate anticoagulant showed significantly lower result for patients compared to controls (-0.36, -0.68 to -0.04). Ischemic stroke patients had higher MPV (0.57, 0.31-0.83), and samples by Ethylenediaminetetraacetic acid (EDTA) anticoagulant showed significantly higher result for patients compared to controls (0.86, 0.55-1.17). PC and MPV appeared to be significantly different between patients with AS and control populations. MPV was significantly higher in ischemic stroke and PC was significantly lower in both ischemic and hemorrhagic strokes. These characteristics might be related to AS and associated with it. It is advisable to pay attention to elapsed time between phlebotomy and hematology analysis, anticoagulant and hemocytometer types in AS. SYSTEMATIC REVIEW REGISTRATION: This meta-analysis is registered on the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42017067864 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=67864).

Factor XIII-A subunit Val34Leu polymorphism in fatal atherothrombotic ischemic stroke.

Factor XIII (FXIII) is a regulator of fibrinolysis and clot firmness. Val34Leu polymorphism of its potentially active A subunit (FXIII-A) leads to faster activation of FXIII, influences clot structure and provides a moderate protection against coronary artery disease. The effect of FXIII-A Val34Leu polymorphism on the risk of atherothrombotic ischemic stroke (AIS) has been investigated in a few studies with contradictory results. In all previous studies, only patients surviving AIS were enrolled and sex-specific effects were not explored. In this retrospective multicenter cohort, we investigated the effect of FXIII-A Val34Leu polymorphism on the risk of fatal AIS in women and men. DNA isolation and genetic determinations in the case of 316 patients who died of AIS were carried out on paraffin-embedded tissue specimens. Genetic analyses for population controls, patients with history of AIS and sex-matched controls were performed on extracted genomic DNA from peripheral blood leukocytes. The prevalence of homozygous wild-type, and heterozygous genotypes, Leu34 carriers and Leu34 allele was not different significantly between the patients with fatal AIS and their respective controls. Logistic regression analysis with age as co-variant demonstrated that in women, homozygous presentation of Leu34 allele represented a more than three-fold increased risk of AIS with fatal outcome. The results demonstrate that FXIII-A Val34Leu polymorphism does not influence the occurrence of AIS, but has an effect on the severity of its outcome. This effect is sex-specific and in homozygous women, the prothrombotic/antifibrinolytic effects of FXIII-A Val34Leu polymorphism seem to prevail.

Vitamin B12 level in peripheral arterial disease.

Hyperhomocysteinemia is considered a risk factor for atherosclerosis. Methyltetrahydrofolate reductase (MTHFR) gene mutation and low level of plasma vitamin B12 and folate could take part in the etiology of peripheral arterial disease (PAD). We examined whether plasma vitamin B12 and folate levels and MTHFR-C677T polymorphism are associated with the risk of PAD. The study comprised 293 patients (107 females, 186 males, mean age of 66 ± SEM0.7 years) and 293 sex-matched control subjects (mean age of 62 ± SEM0.8 years). We also determined plasma lipid profile, hs-CRP, creatinine, vitamin B12, folate and total homocysteine (tHcy) for all patients and controls. Odds ratios were non-significant for different genotypes of MTHFR-C677T polymorphism. There was a significant lower level of vitamin B12 in PAD patients. 43 and 25 % of patient and control populations were in the lowest quartile of vitamin B12 (<188 pmol/L), respectively. Plasma level of vitamin B12 in the lowest quartile significantly increased tHcy level in PAD patients, and it was independent of plasma folate level. Low level of plasma vitamin B12 was independently associated with hyperhomocysteinemia in PAD patients. The prevalence of the MTHFR-C677T mutation was not significantly different in patients with PAD compared with controls.

Prothrombotic polymorphisms in patients with Raynaud's phenomenon and migraine.

We have investigated the prevalence and possible association of inherited prothrombotic risk factors in patients with primary Raynaud's phenomenon (PRP) and migraine. We performed genotypic analysis of FVLeiden, prothrombin G20210A, methyltetrahydrofolate reductase C677T and FXIII-A V34L mutations in these patients. Two hundred patients with primary Raynaud's phenomenon of Hungarian origin with migraine (57 female, one male, mean age of 43.8 ± 11.5 years) or without migraine (101 female, 41 male, mean age of 41.8 ± 14.5 years) were included in this study. Duration of PRP among migrainous patients was significantly longer than patients without migraine. The prevalence of methyltetrahydrofolate reductase T677 allele among patients with migraine was significantly higher than in patients without migraine (odds ratio 2.1, 95% CI: 1.4-3.3, p = 0.001). The prevalence of other thrombosis-associated alleles did not differ between patients with or without migraine. FVLeiden mutation, prothrombin G20210A mutation, and FXIII-A V34L polymorphism have no apparent effect on the occurrence of migraine in PRP.

Correlations between clinicopathological parameters and molecular signatures of primary tumors for patients with stage T3n0 colorectal adenocarcinomas: a single center retrospective study on 100 cases.

BACKGROUND/AIMS: To examine the clinical and protein expression characteristics of tumor tissues for prediction of prognosis in colorectal cancer (CRC). METHODOLOGY: We retrospectively analyzed the clinicopathological data of patients with stage T3N0 CRC, operated between 1997-2003 and the surgical materials for the relation between disease prognosis and p53, p21, p16, ß-catenin, E-cadherin, EGFR, hMLH1, hMSH2 and TS protein expressions. RESULTS: A significantly shorter 3-year disease free survival was observed in patients under the age of 50. The worst 5-year overall survival (OS) observed for patients over 70. Tumor localization and number of processed lymph nodes significantly affected prognosis. The EGFR, hMSH2 and TS expressions and the 5-fluorouracyl treatment were not found to be of prognostic value; p53 and p21 positivity had significantly worse survival. When ß-catenin membrane expression disappeared on tumor cells, the 5-year OS rate decreased and time to metastasis shortened significantly. Membrane ß-catenin expression, processed lymph nodes number and age were detected as independent prognostic markers. CONCLUSIONS: These results suggest that the evaluation of a clinicopathological profile, based on age, tumor localization, number of examined lymph nodes, p53, p21 and E-cadherin ß-catenin expression appears to be useful in identifying high risk patients.

Increased mean platelet volume in primary Raynaud's phenomenon.

We hypothesized that mean platelet volume (MPV), a reliable marker of platelet activation, might be elevated in primary Raynaud's phenomenon (PRP) even if there was no thrombotic complication in our subjects. In this retrospective-cohort study, we examined the clinical value of MPV in 200 patients with PRP and 116 clinical controls, and measured MPV and platelet P-selectin (CD62P) in all study participants. We also evaluated the effect of age, gender, and disease duration on these platelet activation markers in PRP. MPV and CD62 positivities were significantly (p<0.001) elevated in patients with PRP compared with controls. These differences retained when patients and controls were analyzed according to age, gender, and the disease duration. In logistic regression analysis, MPV (OR: 15.8, 95% CI: 8.14-30.64, p<0.001) and CD62P (OR: 11.3, 95% CI: 4.85-26.12, p<0.001) were found to be independently associated with PRP. In conclusion, increased MPV is independently related to PRP, and its level was not influenced by age, gender, and the duration of PRP.

Polymorphism of clotting factors in Hungarian patients with Raynaud's phenomenon.

Patients with primary Raynaud's phenomenon may have a genetically determined risk for clotting factors that predispose them to aberrant microvascular thrombosis. We investigated the prevalence of factor V substitution of G to A at position 1691 (FVLeiden), prothrombin G20210A, and methyltetrahydrofolate reductase C677T mutations in these patients. Two hundred (158 women, 42 men, mean age of 42.4 ± 13.7 years) consecutive patients with primary Raynaud's phenomenon and 200 age-sex-matched healthy controls of Hungarian origin were included in a case-control study. The prevalence of methyltetrahydrofolate reductase C677T homozygous among patients was significantly lower than in the control group (odds ratio 0.4, 95% confidence interval 0.2-0.9, P < 0.05). The prevalence of other thrombosis-associated alleles did not differ between patients with primary Raynaud's phenomenon and control subjects. FVLeiden, prothrombin G20210A, and polymorphism, prothrombin G20210A mutations have no apparent effect on the etiology of primary Raynaud's phenomenon.