Krisztián Vörös

Human serum fetuin A/α2HS-glycoprotein level is associated with long-term survival in patients with alcoholic liver cirrhosis, comparison with the Child-Pugh and MELD scores

BackgroundSerum concentration of fetuin A/α2HS-glycoprotein (AHSG) is a good indicator of liver cell function and 1-month mortality in patients with alcoholic liver cirrhosis and liver cancer. We intended to determine whether decreased serum AHSG levels are associated with long-term mortality and whether the follow-up of serum AHSG levels can add to the predictive value of the Child-Pugh (CP) and MELD scores.MethodsWe determined serum AHSG concentrations in 89 patients by radial immunodiffusion. Samples were taken at the time of enrolment and in the 1st, 3rd, 6th, and the 12th month thereafter.ResultsForty-one patients died during the 1-year follow-up period, 37 of them had liver failure. Data of these patients were analysed further. Deceased patients had lower baseline AHSG levels than the 52 patients who survived (293 ± 77 vs. 490 ± 106 μg/ml, mean ± SD, p < 0.001). Of all laboratory parameters serum AHSG level, CP and MELD scores showed the greatest difference between deceased and survived patients. The cutoff AHSG level 365 μg/ml could differentiate between deceased and survived patients (AUC: 0.937 ± 0.025, p < 0.001, sensitivity: 0.865, specificity: 0.942) better than the MELD score of 20 (AUC: 0.739 ± 0.052, p < 0.001, sensitivity: 0.595, specificity: 0.729). Initial AHSG concentrations < 365 μg/ml were associated with high mortality rate (91.4%, relative risk: 9.874, 95% C.I.: 4.258–22.898, p < 0.001) compared to those with ≥ 365 μg/ml (9.3%). Fourteen out of these 37 fatalities occurred during the first month of observation. During months 1–12 low AHSG concentration proved to be a strong indicator of mortality (relative risk: 9.257, 95% C.I.: 3.945–21.724, p < 0.001). Multiple logistic regression analysis indicated that decrease of serum AHSG concentration was independent of all variables that differed between survived and deceased patients during univariate analysis. Multivariate analysis showed that correlation of low serum AHSG levels with mortality was stronger than that with CP and MELD scores. Patients with AHSG < 365 μg/ml had significantly shortened survival both in groups with MELD < 20 and MELD ≥ 20 (p < 0.0001 and p = 0.0014, respectively).ConclusionSerum AHSG concentration is a reliable and sensitive indicator of 1-year mortality in patients with alcoholic liver cirrhosis that compares well to the predictive value of CP score and may further improve that of MELD score.

Gyakori a magas fokú kiégés a háziorvosok és háziorvosi rezidensek körében

UNLABELLED General practitioners (GPs) play a central role in patient care and are exposed to high levels of work strain and consequent burnout due to the large number of stressful patient-doctor relationships. Despite the high likelihood of burnout among GPs, limited information is available about this topic. AIMS To explore the prevalence of burnout among GPs and residents in Hungary. METHODS Exploratory/descriptive, cross-sectional study with self-administered questionnaires among 453 GPs and 43 residents. To assess burnout, the Maslach Burnout Inventory (MBI-GS) was used. To evaluate the level of burnout, mean (+/- SD) scores on the emotional exhaustion, cynicism/depersonalization, and personal accomplishment dimensions of the MBI were determined among male and female GPs and residents. Differences in the level or degree of burnout (high, intermediate and low) in all three burnout dimensions between male and female GPs and residents were examined by independent samples t -test and chi 2 -tests. Socio-demographic antecedents to burnout were assessed by linear regression analyses. RESULTS Residents reported significantly lower cynicism/depersonalization [ t (df): 2.8 (476); p < 0.01] and personal accomplishment [ t (df): 2.0 (485); p < 0.05] compared to GPs. No gender differences were identified in the level of burnout. Significantly more GPs then residents reported high [chi 2 (df) = 5.9 (1); p < 0.05] or intermediate [chi 2 (df) = 4.6 (1); p < 0.05] degree of depersonalization. Emotional exhaustion, depersonalization, and low personal accomplishment were reported by around 30%, 60%, and 100% of the physicians, respectively. Being a resident emerged as the strongest negative predictor of depersonalization (beta = -0.09, 95% CI -0.22 - -0.002). CONCLUSIONS The prevalence of burnout is high among GPs, and almost all GPs report low degree of personal accomplishment. Residency emerged as a significant protective correlate of depersonalization. These findings provide further data for cross-cultural burnout research.

Association of human fetuin-A rs4917 polymorphism with obesity in 2 cohorts.

Background Previous studies have shown association of the multifunctional hepatic protein α2HS-glycoprotein/human fetuin A with insulin resistance, type 2 diabetes mellitus, metabolic syndrome, obesity, and atherosclerosis. Reports of contribution of α2HS-glycoprotein/human fetuin A rs4917 single-nucleotide polymorphism to the development of these pathologic processes are inconsistent. We aimed to investigate the association between variants of rs4917 and parameters of obesity, lipid status, the proinflammatory cytokine tumor necrosis factor α (TNF-α), adipokines (adiponectin, resistin), and insulin resistance in 2 cohorts. Methods Eighty-one healthy persons (cohort 1) and 157 patients with previous myocardial infarction (cohort 2) were included in this cross-sectional study. rs4917 Polymorphism was determined by the allele-specific KASP by design genotyping assays. Results In cohort 1, T-nucleotide carriers had lower low-density lipoprotein cholesterol levels compared with non-T carriers. The serum concentration of TNF-α was found to be higher carrying the non-T allele in cohort 1; however, this difference was not observed in cohort 2. In cohort 2, T carriers had lower body mass index and abdominal and waist circumferences than did non-T carriers. The T nucleotide was more frequent in nonobese than in obese patients (χ2 = 5.217, P = 0.022). Nonobese, nondiabetic T carriers still had lower body mass index and waist circumference than did non-T carriers. Conclusions Our data suggest that the T nucleotide in rs4917 is associated with more favorable lipid status among healthy persons (i.e., lower low-density lipoprotein cholesterol) and anthropologic parameters of obesity in cohort 2. The protective role of the T allele may also be associated with lower TNF-α levels found in healthy individuals.

Serum ghrelin level and TNF-α/ghrelin ratio in patients with previous myocardial infarction.

BACKGROUND AND AIMS Studies investigating serum ghrelin level in atherosclerosis yielded contradictory results. Interaction of ghrelin with adipocytokines is obscure in cardiovascular diseases. We undertook this study to determine which molecules influence ghrelin level and to see whether post-myocardial infarction (MI) patients have decreased ghrelin levels. METHODS In this cross-sectional study, acyl-ghrelin concentration was determined by radioimmunoassay in sera of 171 patients (ages 62 ± 6 years, mean ± SD) with previous MI and 81 age-matched referent subjects. We evaluated the associations of ghrelin with insulin, adiponectin, leptin, resistin, fetuin-A and tumor necrosis factor-alpha (TNF-α). RESULTS Patients had lower ghrelin levels compared to referent subjects (240.55 ± 59.33 vs. 337.96 ± 30.75 pg/mL, p <0.001) even after excluding diabetic and obese patients (240.63 ± 54.08 vs. 337.96 ± 30.75, p <0.001). In multivariate analysis, insulin (β = -0.327, p <0.001) and adiponectin (β = 0.301, p <0.001) determined ghrelin level (R(2) = 0.199, p <0.001). There was no association between ghrelin and TNF-α levels. In discriminant analysis using ghrelin, adiponectin, leptin, fetuin-A, resistin and TNF-α, the structure matrix revealed ghrelin and TNF-α as strongest predictors for belonging to the patient group (0.760 and -0.569, respectively). Using these two parameters, 89.7% of cases were correctly classified. Subjects with high TNF-α/ghrelin ratio had 11.25 times higher chance for belonging to the patient group (95% CI 5.80-21.80; χ(2) (1) = 215.6, p <0.001) CONCLUSIONS Acylated ghrelin levels are decreased in patients with coronary atherosclerosis, independently of body weight and the presence of type 2 diabetes mellitus. Ghrelin level is determined by elevated insulin and decreased adiponectin levels. Ghrelin alone or in combination with TNF-α may prove to be a novel indicator of coronary atherosclerosis.

[Frequent high-level burnout among general practitioners and residents].

UNLABELLED General practitioners (GPs) play a central role in patient care and are exposed to high levels of work strain and consequent burnout due to the large number of stressful patient-doctor relationships. Despite the high likelihood of burnout among GPs, limited information is available about this topic. AIMS To explore the prevalence of burnout among GPs and residents in Hungary. METHODS Exploratory/descriptive, cross-sectional study with self-administered questionnaires among 453 GPs and 43 residents. To assess burnout, the Maslach Burnout Inventory (MBI-GS) was used. To evaluate the level of burnout, mean (+/- SD) scores on the emotional exhaustion, cynicism/depersonalization, and personal accomplishment dimensions of the MBI were determined among male and female GPs and residents. Differences in the level or degree of burnout (high, intermediate and low) in all three burnout dimensions between male and female GPs and residents were examined by independent samples t -test and chi 2 -tests. Socio-demographic antecedents to burnout were assessed by linear regression analyses. RESULTS Residents reported significantly lower cynicism/depersonalization [ t (df): 2.8 (476); p < 0.01] and personal accomplishment [ t (df): 2.0 (485); p < 0.05] compared to GPs. No gender differences were identified in the level of burnout. Significantly more GPs then residents reported high [chi 2 (df) = 5.9 (1); p < 0.05] or intermediate [chi 2 (df) = 4.6 (1); p < 0.05] degree of depersonalization. Emotional exhaustion, depersonalization, and low personal accomplishment were reported by around 30%, 60%, and 100% of the physicians, respectively. Being a resident emerged as the strongest negative predictor of depersonalization (beta = -0.09, 95% CI -0.22 - -0.002). CONCLUSIONS The prevalence of burnout is high among GPs, and almost all GPs report low degree of personal accomplishment. Residency emerged as a significant protective correlate of depersonalization. These findings provide further data for cross-cultural burnout research.

The role of fetuin-A in cardiovascular diseases

Fetuin-A (also known as α2-Heremans-Schmid glycoprotein) is a multifunctional molecule secreted by the liver. It is a negative acute phase reactant with a debated role in subclinical inflammation. Fetuin-A is an inhibitor of the insulin receptor and its serum level correlates with insulin resistance. The protein has been implicated in adipocyte dysfunction and it is associated with obesity and non-alcoholic fatty liver disease. Although all these properties seem to promote atherosclerosis, the role of fetuin-A in cardiovascular diseases is more complex. As a natural inhibitor of tissue and vascular calcification, fetuin-A also acts as a protective factor in atherosclerosis. The potential role and prognostic value of fetuin-A in arterial calcification and cardiovascular diseases is discussed in this review, along with explanations for seemingly contradicting results in the literature and possible directions for future research.

Human fetuin-A Rs4918 polymorphism and its association with obesity in healthy persons and in patients with myocardial infarction in two Hungarian cohorts

Background Human fetuin A (AHSG) has been associated with the development of obesity, insulin resistance, type 2 diabetes mellitus, and atherosclerosis. Observations on the role of AHSG rs4918 single-nucleotide polymorphism are contradictory. We investigated the association between variants of rs4918 and parameters of obesity, lipid status, tumor necrosis factor-α (TNFα), adipokines (adiponectin, resistin, leptin), and insulin resistance in healthy persons and in patients with previous myocardial infarction. Material/Methods This was a cross-sectional study comprising cohort 1 (81 healthy individuals) and cohort 2 (157 patients with previous myocardial infarction). We used the allele-specific KASP genotyping assay to detect rs4918 polymorphism. Results In cohort 1, G-nucleotide carriers had significantly lower serum TNFα, adiponectin, and higher leptin concentrations than in non-G carriers. These differences, however, were not observed in cohort 2. In cohort 2, G-carriers had lower BMI and waist circumferences than in non-G carriers. The G allele was more frequent among lean than obese patients (RR=1.067, 95%CI=1.053–2.651, p=0.015). An association between BMI and rs4918 polymorphism was observed among patients without diabetes (CC/CG/GG genotypes: p=0.003, G vs. non-G allele: p=0.008) but not in diabetics. In addition, a strong linearity between BMI and the CC/CG/GG genotypes (association value: 4.416, p=0.036) and the frequency of the G allele (7.420, p=0.006) could be identified. In cohort 2, non-obese, non-diabetic G-carriers still had lower BMI and waist circumferences than in non-G carriers. Conclusions The rs4918 minor variant is associated with lower TNFα and adiponectin, higher leptin levels in healthy persons, and more favorable anthropomorphic parameters of obesity in cohort 2.

Association of PPAR Alpha Intron 7 G/C, PPAR Gamma 2 Pro12Ala, and C161T Polymorphisms with Serum Fetuin-A Concentrations

Background Both peroxisome activator proteins (PPARs) and fetuin-A play a role in lipid and glucose metabolism. Aims We investigated whether PPARα intron 7 G2468/C and PPARγ2 Pro12Ala and PPARγ exon 6 C161T polymorphisms are associated with serum fetuin-A concentrations. Patients and Methods The PPARα intron 7 G/C polymorphism was studied in cohort 1 (79 reference individuals, 165 postinfarction patients). The two PPARγ polymorphisms were investigated in cohort 2 (162 reference individuals, 165 postinfarction patients). Fetuin-A levels and PPAR polymorphisms were determined by radial immunodiffusion and polymerase chain reaction-restriction fragment length polymorphism techniques. Results The C allele variant of PPARα intron 7 G2467C was associated with higher fetuin-A levels (p = 0.018). Postinfarction status (p = 0.001), PPARα intron 7 GG/GC/CC genotypes (p = 0.032), and the C allele (p = 0.021) were the strongest determinants of fetuin-A concentration in a multiple regression model. Higher fetuin-A levels were associated with the Pro variant of PPARγ2 (p = 0.047). Postinfarction status (p = 0.041) and BMI (p < 0.001) but not PPARγ2 Pro were the strongest determinants of fetuin-A concentrations. PPARγ exon 6 C161T genotypes were not associated with fetuin-A levels. Conclusions Fetuin-A was determined mainly by the PPARα intron 7C allele and postinfarction status in cohort 1 and the BMI and postinfarction in cohort 2. The PPARα intron 7C and PPARγ2 Pro variants are associated with fetuin-A levels.

Gyakori a magas fokú kiégés a háziorvosok és háziorvosi rezidensek körében = Frequent occurance of level burnout among general practitioners and residents

UNLABELLED General practitioners (GPs) play a central role in patient care and are exposed to high levels of work strain and consequent burnout due to the large number of stressful patient-doctor relationships. Despite the high likelihood of burnout among GPs, limited information is available about this topic. AIMS To explore the prevalence of burnout among GPs and residents in Hungary. METHODS Exploratory/descriptive, cross-sectional study with self-administered questionnaires among 453 GPs and 43 residents. To assess burnout, the Maslach Burnout Inventory (MBI-GS) was used. To evaluate the level of burnout, mean (+/- SD) scores on the emotional exhaustion, cynicism/depersonalization, and personal accomplishment dimensions of the MBI were determined among male and female GPs and residents. Differences in the level or degree of burnout (high, intermediate and low) in all three burnout dimensions between male and female GPs and residents were examined by independent samples t -test and chi 2 -tests. Socio-demographic antecedents to burnout were assessed by linear regression analyses. RESULTS Residents reported significantly lower cynicism/depersonalization [ t (df): 2.8 (476); p < 0.01] and personal accomplishment [ t (df): 2.0 (485); p < 0.05] compared to GPs. No gender differences were identified in the level of burnout. Significantly more GPs then residents reported high [chi 2 (df) = 5.9 (1); p < 0.05] or intermediate [chi 2 (df) = 4.6 (1); p < 0.05] degree of depersonalization. Emotional exhaustion, depersonalization, and low personal accomplishment were reported by around 30%, 60%, and 100% of the physicians, respectively. Being a resident emerged as the strongest negative predictor of depersonalization (beta = -0.09, 95% CI -0.22 - -0.002). CONCLUSIONS The prevalence of burnout is high among GPs, and almost all GPs report low degree of personal accomplishment. Residency emerged as a significant protective correlate of depersonalization. These findings provide further data for cross-cultural burnout research.

Frequent occurance of level burnout among general practitioners and residents

UNLABELLED General practitioners (GPs) play a central role in patient care and are exposed to high levels of work strain and consequent burnout due to the large number of stressful patient-doctor relationships. Despite the high likelihood of burnout among GPs, limited information is available about this topic. AIMS To explore the prevalence of burnout among GPs and residents in Hungary. METHODS Exploratory/descriptive, cross-sectional study with self-administered questionnaires among 453 GPs and 43 residents. To assess burnout, the Maslach Burnout Inventory (MBI-GS) was used. To evaluate the level of burnout, mean (+/- SD) scores on the emotional exhaustion, cynicism/depersonalization, and personal accomplishment dimensions of the MBI were determined among male and female GPs and residents. Differences in the level or degree of burnout (high, intermediate and low) in all three burnout dimensions between male and female GPs and residents were examined by independent samples t -test and chi 2 -tests. Socio-demographic antecedents to burnout were assessed by linear regression analyses. RESULTS Residents reported significantly lower cynicism/depersonalization [ t (df): 2.8 (476); p < 0.01] and personal accomplishment [ t (df): 2.0 (485); p < 0.05] compared to GPs. No gender differences were identified in the level of burnout. Significantly more GPs then residents reported high [chi 2 (df) = 5.9 (1); p < 0.05] or intermediate [chi 2 (df) = 4.6 (1); p < 0.05] degree of depersonalization. Emotional exhaustion, depersonalization, and low personal accomplishment were reported by around 30%, 60%, and 100% of the physicians, respectively. Being a resident emerged as the strongest negative predictor of depersonalization (beta = -0.09, 95% CI -0.22 - -0.002). CONCLUSIONS The prevalence of burnout is high among GPs, and almost all GPs report low degree of personal accomplishment. Residency emerged as a significant protective correlate of depersonalization. These findings provide further data for cross-cultural burnout research.