Combined GSTM1 and GSTT1 null genotypes are strong risk factors for atherogenesis in a Serbian population.

Oxidative stress (OS) plays an important role in atherogenesis and since glutathione S-transferases (GSTs) provide protection against OS, we have tested the hypothesis that deletion polymorphisms in two GSTs (GSTM1 and GSTT1) may affect the risk of developing atherosclerosis. A total of 382 individuals (200 patients with atherosclerosis and 182 healthy controls) were included in this association study. Genomic DNA was isolated from peripheral blood cells or from buccal epithelial cells and genotyping was performed using multiplex-PCR or real-time PCR methods. GSTM1 null genotype was significantly more frequent in atherosclerotic patients than in controls (52.0% vs 34.1%) and individuals with the GSTM1 null genotype had an approximately 2-fold increase in atherosclerosis risk (OR: 2.1, 95%CI=1.39-3.17, P=0.0004). GSTT1 null genotype alone did not show a statistically significant effect on atherosclerosis risk modulation, but the association approached significance (OR: 1.57, 95%CI=0.94-2.64, P=0.08). The combined analysis showed that the presence of both genes had a protective effect against atherosclerosis (OR=0.55, 95%CI=0.37-0.83, P=0.005) while double null genotypes led to a robust atherosclerosis risk increase (OR: 8.14, 95%CI= 2.41-27.51, P < 0.0001). This study demonstrated that the GSTM1 null and combined GSTM1/GSTT1 null genotypes are susceptibility factors for development of atherosclerosis in a Serbian population.

TNF-α (-308G>A) and TNF-R1 (36A>G) single nucleotide polymorphisms are strong risk factors for odontogenic keratocystic tumor development.

BACKGROUND: Polymorphisms in genes encoding tumor necrosis factor-α (TNF-α) and its receptor TNF-R1 have been shown to affect one person's susceptibility to develop certain neoplastic diseases. The aim of the present association study was to investigate whether single nucleotide polymorphisms (SNPs) in TNF-α (-308G>A) and TNF-R1 (36A>G) genes modulate the susceptibility for keratocystic odontogenic tumors (KCOTs) development in Serbian patients. METHODS: Genotyping was performed in 60 KCOT patients and 125 healthy individuals, using polymerase chain reaction/restriction fragment length polymorphism analysis. RESULTS: A significant difference in genotype and allele frequencies was found between patients and controls for both SNPs (P < 0.05). Carriers of the TNF-α A variant had an eightfold increase of KCOT risk (OR = 8.12, 95% CI = 3.98-16.56, P < 0.0001), while carriers of the TNF-R1 G variant had approximately a fourfold increase of KCOT risk (OR=3.65, CI: 1.60-8.40, P = 0.001). CONCLUSIONS: Our findings suggest that the two polymorphisms are strong risk factors for KCOT development in Serbian population.

External Validation of the Simple NULL-PLEASE Clinical Score in Predicting Outcome of Out-of-Hospital Cardiac Arrest.

BACKGROUND: Rapid clinical decision-making on further management of patients with out-of-hospital cardiac arrest may be challenging. Recently, a "futility" score (NULL-PLEASE) incorporating multiple adverse resuscitation features (Nonshockable rhythm, Unwitnessed arrest, Long no-flow or Long low-flow period, blood PH <7.2, Lactate >7.0 mmol/L, End-stage chronic kidney disease on dialysis, Age ≥85 years, Still resuscitation, and Extracardiac cause) has been proposed to help identify patients with out-of-hospital cardiac arrest unlikely to survive; however, external independent score validation is lacking. METHODS: We retrospectively validated the NULL-PLEASE predictive ability for early in-hospital outcome of out-of-hospital cardiac arrest in a single-center cohort of 547 consecutive patients with out-of-hospital cardiac arrest who were admitted from April 2013 to October 2016 (mean age, 66.3 ± 13.2 years); 227 patients (41.5%) died. Because pH and lactate were inconsistently measured, a modified NULL-PLEASE score excluding both variables was calculated as the principal analysis. A sensitivity analysis included the subgroup with pH data available (n = 177). RESULTS: Long low-flow period and age ≥85 years were independently associated with fatal outcome (both P < .001). Patients with a modified NULL-PLEASE score of ≥5 had a 3.3-fold greater risk of fatal outcome compared with a score of 0 to 4 (odds ratio, 3.34; 95% confidence interval [CI], 2.29-4.89; P < .001); 77% of nonsurvivors had a score ≥5; NULL-PLEASE showed a modest predictive ability for fatal outcome (c-statistic 0.658; 95% CI, 0.613-0.704; P < .001). Sensitivity analysis yielded similar results, with 88% of nonsurvivors having a score ≥5. CONCLUSIONS: The NULL-PLEASE score was predictive for early in-hospital outcome of out-of-hospital cardiac arrest, with a 3.3-fold greater odds for fatal outcome at the score values of ≥5.

Combined GSTM1 and GSTT1 null genotypes are strong risk factors for atherogenesis in a Serbian population

Abstract Oxidative stress (OS) plays an important role in atherogenesis and since glutathione S-transferases (GSTs) provide protection against OS, we have tested the hypothesis that deletion polymorphisms in two GSTs (GSTM1 and GSTT1) may affect the risk of developing atherosclerosis. A total of 382 individuals (200 patients with atherosclerosis and 182 healthy controls) were included in this association study. Genomic DNA was isolated from peripheral blood cells or from buccal epithelial cells and genotyping was performed using multiplex-PCR or real-time PCR methods. GSTM1 null genotype was significantly more frequent in atherosclerotic patients than in controls (52.0% vs 34.1%) and individuals with the GSTM1 null genotype had an approximately 2-fold increase in atherosclerosis risk (OR: 2.1, 95%CI=1.39-3.17, P=0.0004). GSTT1 null genotype alone did not show a statistically significant effect on atherosclerosis risk modulation, but the association approached significance (OR: 1.57, 95%CI=0.94-2.64, P=0.08). The combined analysis showed that the presence of both genes had a protective effect against atherosclerosis (OR=0.55, 95%CI=0.37-0.83, P=0.005) while double null genotypes led to a robust atherosclerosis risk increase (OR: 8.14, 95%CI= 2.41-27.51, P < 0.0001). This study demonstrated that the GSTM1 null and combined GSTM1/GSTT1 null genotypes are susceptibility factors for development of atherosclerosis in a Serbian population.

Myocardial reinfarction in a patient with coronary ectasia.

A 47-year-old male patient was admitted to our Emergency Hospital's coronary unit with an acute myocardial infarction, localized inferolaterally. He had been hospitalized 2 months before this occurrence because of persistent chest pain accompanied by elevation of the ST segment in precordial and inferior leads, for which he received thrombolytic therapy. Selective cardiac catheterization was then also effected, and showed diffuse ectasia of coronary arteries with no significant stenoses. Since streptokinase had been applied recently, the patient was given standard therapy as well as electroshocks because of chamber fibrillation. Two hours after admission, the infarct pain ceased and rapid ECG improvement occurred. Repeated coronarography showed a situation identical to the previous one. The patient was sent home to proceed with drug therapy.