Efficacy of amiodarone for the prevention of atrial fibrillation recurrence after cardioversion.

The restoration and maintenance of sinus rhythm is a desirable strategy for many patients with atrial fibrillation (AF) since it has been associated with improvement in symptoms and a better quality of life. Sinus rhythm can be achieved by pharmacological or electrical cardioversion or after catheter ablation of AF. Despite high rates of successful cardioversion, AF recurrence remains a major challenge. Anti-arrhythmic drug therapy currently plays a significant role in maintaining sinus rhythm after cardioversion. Amiodarone is the most commonly prescribed anti-arrhythmic drug for patients with AF. This is due to its particular electrophysiological properties and superior anti-arrhythmic effects in comparison with other anti-arrhythmic drugs. Understanding the cardiac electrophysiology and arrhythmogenesis mechanisms may result in identification of new targets for anti-arrhythmic therapy. The aim of this article was to review amiodarone's clinical pharmacology and evaluate evidence supporting amiodarone for treatment and prevention of AF recurrence after cardioversion.

Evaluation of prognostic factors for 5 year-survival after surgery for colorectal cancer.

AIM: The aim of this study was to assess and analyze the prognostic factors for survival in patients undergoing curative surgery for colorectal cancer and to identify new prognostic factors. METHODS: The prospective study included 301 patients diagnosed with colorectal cancer, stages I-III, undergoing curative surgery. Demographic data, clinical and anamnestic data, laboratory exams, paraclinical examinations, morphological and pathological examination were recorded. The Petersen index was calculated. Tumor necrosis, desmoplasia and mucinous component were assessed. Local inflammatory response was calculated using Klintrup criteria. Patients were followed for five years after surgery. RESULTS: There were 197 patients (66.4%) who survived and 104 patients (34.6%) who died during the 5-year follow- up period. Multivariate analysis showed that death was mostly associated with patients over 60 years of age (p=0.05). Tumor location within the colon was associated with a better survival than tumor location within the rectum (HR - 0.57; p=0.02). Patients with T>2 had a poor prognosis compared to those with T=<2 (HR - 2.23; p=0.02). Patients with Klintrup score >1 had a better prognosis (HR - 0.20; p <0.001). Patients with venous invasion showed significantly worse prognosis (HR - 2.26; p=0.003). Patients with desmoplasia score 3 had lower death rates than those with score 1 (HR - 0.42; p=0.01). CONCLUSION: Survival was superior in patients with cancer of the colon. The following parameters had a strong independent prognostic factor for survival: age, stage T>2, venous invasion, mucinous component and desmoplasia. KEY WORDS: Colorectal cancer, Prognostic factors, Survival.

Resistin and Cardiac Arrest-A Prospective Study.

. The systemic response to ischemia-reperfusion that occurs after a cardiac arrest (CA) followed by the return of spontaneous circulation leads to endothelial toxicity and cytokine production, both responsible for the subsequent occurrence of severe cardiocirculatory dysfunction and early death. Resistin is emerging as a biomarker of proinflammatory status and myocardial ischemic injury and as a mediator of endothelial dysfunction. The study aimed to analyze the possible associations between several clinical and biological variables and the serum levels of resistin in CA survivors. Forty patients with out-of-hospital resuscitated CA, were enrolled in the study. Demographic, clinical and laboratory data (including serum resistin measurements at admission and at 6, 12, 24, 48 and 72 h) were recorded. For resistin, we calculated the area under the curve (AUC) using the trapezoidal method with measurements from 0 to 12 h, 0 to 24 h, 0 to 48 h and 0 to 72 h. Fifteen (37.5%) patients died in the first 72 h after CA. Cardiovascular comorbidities were present in 65% of patients. The majority of patients had post-CA shock (29 (72.5%)). Resistin serum levels rose in the first 12-24 h and decreased in the next 48-72 h. In univariate analysis, advanced age, longer duration of resuscitation, high sequential organ failure assessment score, high lactate levels, presence of cardiovascular comorbidities and the post-CA shock were associated with higher resistin levels. In multivariate analysis, post-CA shock or cardiovascular comorbidities were independently associated with higher AUCs for resistin for 0-12 h and 0-24 h. The only identified variable to independently predict higher AUCs for resistin for 0-48 h and 0-72 h was the presence of post-CA shock. Our data demonstrate strong independent correlation between high serum resistin levels, cardiac comorbidities and post-CA shock. The impact of the post-CA shock on serum concentration of resistin was greater than that of cardiac comorbidities.

Determination of Cut-off Serum Values for Resistin and S100B Protein in Patients Who Survived a Cardiac Arrest.

INTRODUCTION: In an attempt to identify patients who have successfully survived a resuscitated cardiac arrest (CA), attention is drawn to resistin and S100B protein, two biomarkers that have been studied in relation to CA. AIM: The study aimed to identify the potential cut-off serum values for resistin and S100B in patients who had CA, compared to healthy volunteers, given that, currently, none of the markers have normal and pathological reference range limits for human assay levels related to this pathology. MATERIALS AND METHODS: Forty patients, resuscitated after out-of-hospital CA and forty healthy controls, were included in the study. All patients were followed up for seventy-two hours after CA or until death. Blood samples for biomarkers were collected on admission to the ED (0-time interval) and at 6, 12, 24, 48 and 72 hours following resuscitation. Only one blood sample was collected from the controls. The serum concentrations of biomarkers were measured. RESULTS: For each time interval, median serum levels of resistin and S100 B were ​ significantly higher in patients with CA compared to healthy controls. The cut-of value for resistin in patients with CA, at the 12-hours versus controls, was > 8.2 ng/ml. The cut-of value for S100B in patients with CA versus controls recorded at 6 hours, was > 11.6 pg/ml. CONCLUSION: Serum levels of resistin and S100B are higher among resuscitated CA patients compared to controls.

The prognostic role of microsatellite instability in colorectal cancer patients.

BACKGROUND: Data from the literature regarding the prognostic role of DNA mismatch repair system (MMR) in colorectal cancer are still controversial. AIM: The aim of the study was to identify the prognostic role of different phenotypic, clinical and pathological characteristics in microsatellite unstable vs. microsatellite stable colorectal cancer in terms of survival and disease free interval. METHODS: We conducted a retrospective study that included a total of 103 patients who underwent curative surgery for colorectal cancer. Immunohistochemistry testing revealed MLH1, MLH2, MLH6, PMS2 genes and mutations of the BRAF gene. We identified three groups of patients: patients with colorectal tumors with MSI produced by hypermethylation, (MLH1/BRAF+) group, patients with microsatellite instable tumours produced by genetic mutations MSI groupb(MLH1, MLH2, MLH6, PMS2) and patients with microsatellite stable tumours (MSS). RESULTS: The study shows that: MSI tumours (MLH1/BRAF+) group occur more frequently in women (p=0.05), on the right side of the colon (p=0.001). The 5-year survival rate was higher in patients with MSI tumours (MLH1/BRAF+) group than in those with microsatellite stable tumours, the differences were not statistically significant ; relapse rate was higher in patients with MSI tumors than in those with MSI tumours (MLH1/BRAF+) group (p=0.03) or with MSS tumors (p=0.004). CONCLUSIONS: The identification of microsatellite unstable colorectal tumours is an important molecular marker with role in recognition subgroups of patients with different phenotypic characteristics, survival and relapse rates. KEY WORDS: Colorectal cancer, Mismatch repair genes, Prognostic role.

VKORC1-1639 G>A Polymorphism and the Risk of Non-Variceal Upper Gastrointestinal Bleeding.

BACKGROUND AND AIMS: The mutations in the gene that encodes vitamin K epoxide reductase (VKOR) enzyme are responsible for low levels of vitamin K. The purpose of this study was to evaluate whether the presence of the VKORC1 -1639 G> A polymorphism is a risk factor for non-variceal upper gastrointestinal bleeding (UGIB) in patients without concomitant therapy with vitamin K antagonists. METHODS: This case-control study comprised 163 consecutive patients diagnosed with UGIB and 178 controls, in whom the diagnosis of UGIB was excluded. The following data were recorded: age, gender, alcohol consumption, smoking, history of UGIB, nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin consumption. Genetic analysis included genotyping for the VKORC1 -1639 G>A polymorphism. RESULTS: History of UGIB (OR 3.463, CI95% 1.463-8.198, p=0.005), smoking (OR 2.498, CI95% 1.358-4.597, p=0.003), alcohol consumption (OR 3.283, CI95% 1.796-6.000, p<0.001), use of NSAIDs (OR 4.542, CI95% 2.502-8.247, p<0.001) or of low-dose aspirin (OR 2.390, CI95% 1.326-4.310), and the VKORC1 -1639 G> A AA genotype (OR 1.364, CI95% 0.998-1.863, p=0.05) were associated with an increased risk of UGIB. The risk of UGIB was analyzed in patients with genotype AA who used aspirin or NSAIDs. The genotype AA has not kept its status of independent risk factor (p=0.3). In subjects with NSAIDs/aspirin therapy and genotype AA there was a two times higher chance of UGIB compared to those under NSAIDs/aspirin therapy alone (OR 7.6 vs. 3.6, p<0.001). CONCLUSION: Patients with non-variceal UGIB caused by the use of NSAIDs or low-dose aspirin are more frequent carriers of the VKORC1 -1639 G>A AA genotype, as compared to those without UGIB.

In Vivo Anti-Inflammatory Effect of H1 Antihistamines in Allergic Rhinitis: A Randomized Clinical Trial.

BACKGROUND: Allergic rhinitis is characterized by a chronic inflammation of nasal mucosa and represents a risk factor for asthma occurrence. H1 antihistamines reduce the symptoms of rhinitis, but some compounds may have anti-inflammatory properties. AIMS: We evaluated the plasma level of some cytokines in patients with persistent allergic rhinitis (PAR) and their evolution after a 4-week treatment with H1 anti-histamines, as well as the risk of asthma after 1.5 years. STUDY DESIGN: Randomized clinical trial. METHODS: Eighty-five patients with PAR and 30 healthy volunteers were included in the study. The patients with PAR were randomly divided into 2 groups: 41 patients treated with 5 mg/day desloratadine and 44 patients under 5 mg/day levocetirizine for 4 weeks. The clinical and biological evaluations were performed before and after treatment and included rhinitis symptoms and total symptoms score, type of sensitization, and plasmatic levels of total IgE, IL-1ß, IL-6, IL-8 and TNF-α. RESULTS: IL-8 and TNF-α were significantly increased in patients with PAR compared to healthy volunteers (5.85 vs 3.12, p<0.001 and 2.32 vs 1.06, p<0.001, respectively). Both H1 antihistamines reduce all symptoms of allergic rhinitis, including nasal congestion and the plasmatic level of IL-1ß, IL-6, IL-8 and TNF-α, after 4 weeks of treatment. The reduction of cytokine levels was not influenced by patients' age, sex, duration or severity of rhinitis, or type of sensitization. Levocetirizine has a superior effect compared to desloratadine in reducing the rhinitis symptoms and cytokines' level. Twenty eight (32.9%) of the patients presented asthma symptoms after 1.5 years. The occurrence of asthma was influenced by house dust sensitization (OR-14.6; CI 95% 1.8-116.3; p=0.01), but baseline values of cytokines were not predictive factors for its appearance. CONCLUSION: Levocetirizine and desloratadine as a prolonged therapy reduce plasmatic levels of some pro-inflammatory cytokines in patients with PAR. Levocetirizine has a better effect on decreasing the symptoms and plasmatic levels of IL-1ß and IL-8. (ClinicalTrials. gov Identifier: NCT02507635). FOUNDING: POSDRU and University of Medicine and Pharmacy, Iuliu Hatieganu, Cluj Napoca.

Serum homocysteine levels, oxidative stress and cardiovascular risk in non-alcoholic steatohepatitis.

INTRODUCTION: Hyperhomocysteinemia is considered an independent risk factor for cardiovascular disease. Oxidative stress is one of the major pathogenic mechanisms in non-alcoholic fatty liver disease and atherosclerosis. AIM: Our study aimed to evaluate serum homocysteine levels and oxidative stress in patients with biopsy-proven non-alcoholic steatohepatitis and possible association with cardiovascular risk measured by carotid artery intima-media thickness (c-IMT). PATIENTS AND METHODS: 50 patients with non-alcoholic steatohepatitis and 30 healthy controls, age and gender matched, were recruited. Lipid profile, liver biochemical markers, serum homocysteine, vitamins B6 and B12, folic acid, glutathione (reduced and total), erythrocyte superoxide dismutase, whole blood glutathione peroxidase, malondialdehyde and carotid intima-media thickness were assayed. RESULTS: Patients had an altered lipid profile and liver biochemical markers; carotid intima-media thickness and serum homocysteine levels were significantly higher compared to controls, but there were no differences in folate, B12 and B6 vitamins levels. Patients had significantly lower levels of glutathione peroxidase activity, total and reduced glutathione and higher levels of malondialdehyde, but unchanged superoxide dismutase activity compared to control group. Also, serum homocysteine level showed significant positive correlation with waist circumference, body mass index, free cholesterol, triglycerides, LDL-cholesterol, amino transferases and negative correlation with reduced and total glutathione, superoxide dismutase and γ-GT. CONCLUSION: Non-alcoholic steatohepatitis is an independent cardiovascular risk factor, associated with elevated homocysteine levels, oxidative stress and c-IMT. c-IMT could be used as an indicator of early atherosclerotic changes initiated by dyslipidemia and oxidative stress, while higher level of homocysteine might be an effect of liver damage.

The relationship between factor V Leiden, prothrombin G20210A, and MTHFR mutations and the first major thrombotic episode in polycythemia vera and essential thrombocythemia.

Arterial and venous thrombosis are the most frequent complications in patients with polycythemia vera and essential thrombocythemia. We sought to demonstrate a possible contribution of the factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) 677 C > T and 1298 A > C mutations to the thrombotic risk in patients with polycythemia vera and essential thrombocythemia along with other biological features of these patients. We included 86 patients with polycythemia vera, of which 34 (39.5 %) had major thrombosis and 95 patients with essential thrombocythemia, of which 22 (23.1 %) had major thrombosis. In the whole cohort of patients, only the factor V Leiden mutation was significantly associated with both arterial and venous thrombosis in univariate and multivariate analysis (odds ratio (OR) = 4.3; 95 % confidence interval (CI) = 1.5-12.5; p = 0.008 and OR = 4.3; 95 % CI = 1.2-15.9; p = 0.02, respectively). Other factors significantly associated with thrombosis in both univariate and multivariate analysis were male sex (OR = 2.8, 95 % CI = 1.4-5.4, p = 0.002 and OR = 3.5, 95 % CI = 1.6-7.6, p = 0.002, respectively) and the JAK2 V617F mutation (OR = 5.5, 95 % CI = 2.1-15, p = 0.0001 and OR = 6.9, 95 % CI = 2.2-21.2, p = 0.001, respectively). In conclusion, among the four mutations analyzed (factor V Leiden, prothrombin G20210A, and MTHFR 677 C > T and 1298 A > C), only factor V Leiden is a major contributor to thrombosis in polycythemia vera and essential thrombocythemia.