Time course of asymmetric dimethylarginine (ADMA) and oxidative stress in fructose-hypertensive rats: a model related to metabolic syndrome

ObjectiveAsymmetric dimethylarginine (ADMA) is an endogenous modulator of endothelial function and oxidative stress, and increased levels of this molecule have been reported in some metabolic disorders and cardiovascular diseases. The aim of this work was to analyze the time course of dimethylarginine compounds and oxidative stress levels and the relationship between these and cardiovascular function in fructose-hypertensive rats.Methods and results90 male Sprague–Dawley rats were randomized into 2 groups, fed for 3 months with standard (C) chow supplemented or not with fructose (F, 60%). After sacrifice at different weeks (W), the aorta and plasma were harvested to assess the vascular and biochemical parameters. Our work showed that the plasma levels of ADMA in the fructose-fed rats increased after 2 weeks of the diet (1.6 ± 0.3 μM vs. 1.2 ± 0.3 μM, p < 0.05) with no changes in plasma levels of either SDMA or l-arginine and after an increase in glycemia. Levels of vascular oxidative stress, estimated in aortic segments using an oxidative fluorescence technique, were higher in the F group (W2: 1.14 ± 0.2% vs. 0.33 ± 0.02%, p < 0.01). An increase in expression levels of nitrotyrosine (3-fold) and iNOS (2-fold) were noted in the fructose-fed rats. After 1 month, this was associated with a significant increase in NAD(P)H oxidase activity. Concerning vascular function, a 15% decrease in maximal endothelium-dependent relaxation was found in the aorta of the F group. Our work showed that the presence of exogenous L-MMA, an inhibitor of NO synthase, was associated with a significant reduction in endothelium-dependent relaxation in isolated aorta rings of the C group; this effect was not observed in the vessels of fructose-fed rats.ConclusionOur findings suggest that the elevated levels of ADMA observed could in part be secondary to the early development of oxidative stress associated with the development of hypertension.     

The biological effect of pharmacological treatment on dimethylaminohydrolases (DDAH-1) and cationic amino acid transporter-1 (CAT-1) expression in patients with acute congestive heart failure

AimAsymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) which plays an important role in controlling vascular tone and regulates the contractile properties of cardiac myocytes. The aim of this study was to investigate the effect of pharmacological treatment on symmetric dimethylarginine (SDMA), ADMA and arginine plasma concentrations in patients with acute congestive heart failure (ACHF) through the evaluation of type-1 system cationic amino acid transporter-1/type 1 dimethylarginine dimethylaminohydrolases-1 (CAT-1/DDAH-1).Methods and results25 hospitalized cardiology patients with symptomatic acute congestive HF (NYHA Class III-IV) and impaired left ventricular (LV) function (ejection fraction < 35%) were included in the study. ADMA, SDMA, and arginine plasma concentrations were assessed before and after pharmacological treatment by high performance liquid chromatography. All patients received an adequate pharmacological treatment for ACHF. ADMA and SDMA plasma levels were significantly higher after pharmacological treatment respect to baseline values (pre-treatment) (0.75 vs 0.48; 1.31 vs 1.03; p < 0.01). Arginine plasma concentration was significantly lower after therapy respect to baseline values (0.78 vs 0.99; p < 0.01). This is associated more with the modulation of DDAH-1 protein than with of CAT-1 system transport.ConclusionsIn patients with ACHF, acute renal impairment function and the modulation of metabolism and extracellular transport by the DDAH-1/CAT-1 system determine high ADMA and SDMA levels after therapy for acute congestive heart failure.     

Circulating homocysteine levels in patients with type 2 diabetes mellitus

Background and aimPrevious studies have shown conflicting results regarding circulating homocysteine levels in patients with type 2 diabetes.Methods and resultsThis observational study included 2121 patients with angiographically proven coronary artery disease (507 patients with type 2 diabetes and 1614 patients without diabetes). Circulating homocysteine levels, methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, renal function, presence of coronary artery disease (CAD) diagnosed by coronary angiography, and circulating folate and vitamin B₁₂ status were assessed. Plasma homocysteine levels [median (25th; 75th percentile)] were significantly higher in patients with diabetes than in those without [12.4 μmol/L (9.9 μmol/L; 15.9 μmol/L) versus 11.7 μmol/L (9.6 μmol/L; 14.5 μmol/L), P = 0.011]. Diabetes affected homocysteine levels only in patients with a glomerular filtration rate <90 mL/min [13.0 μmol/L (10.5 μmol/L; 16.7 μmol/L) in patients with diabetes versus 12.2 μmol/L (10.1 μmol/L; 15.2 μmol/L) in patients without diabetes, P = 0.006] but not in those with a glomerular filtration rate ≥90 mL/min [10.1 μmol/L (8.1 μmol/L; 12.4 μmol/L) versus 10.2 μmol/L (8.8 μmol/L; 12.3 μmol/L), P = 0.267]. Multivariable analysis did not show an independent association between diabetes and homocysteine level (P = 0.342).ConclusionCirculating homocysteine levels are increased in patients with type 2 diabetes compared with non-diabetic patients due to a more diabetes-associated adverse risk profile rather than to diabetes itself.     

Plasma asymmetric dimethylarginine concentrations in sickle cell disease are related to the hemolytic phenotype

Asymmetric dimethylarginine (ADMA) is associated with pulmonary hypertension (PHT) in sickle cell disease (SCD). We studied the relationship of ADMA to other SCD-related complications. Plasma ADMA and associated parameters were determined in 52 HbSS/HbSβ⁰-thalassemia and 24 HbSC/HbSβ⁺-thalassemia patients. As expected ADMA levels were higher in HbSS/HbSβ⁰-thalassemia patients with PHT (p = 0.018), but also in those with other hemolysis-associated complications such as leg ulcers (p = 0.012), cholelithiasis (p = 0.008) and priapism (p = 0.02) compared with counterparts without these complications. ADMA levels did not differ between patients with and without other disease related complications such as retinopathy and avascular osteonecrosis. Higher ADMA concentrations therefore seem to be associated to the hemolytic phenotype of SCD.     

The relation of serum gamma-glutamyl transferase levels with coronary lesion complexity and long-term outcome in patients with stable coronary artery disease

BackgroundRelation of serum gamma-glutamyl transferase (GGT) levels with extent, severity, and complexity of coronary artery disease has not been adequately studied. Therefore, we evaluated the relationship between GGT levels and coronary complexity, severity and extent assessed by SYNTAX score and long-term adverse events.MethodsWe enrolled 442 consecutive patients with stable angina pectoris who underwent coronary angiography. Baseline serum GGT levels were measured and SYNTAX score was calculated from the study population. Median follow-up duration was 363 days. Endpoints were all cause mortality and any revascularization.ResultsGGT levels demonstrated an increase from low SYNTAX tertile to high tertile. In multivariate analysis serum GGT, diabetes mellitus, HDL-cholesterol, eGFR and ejection fraction were found to be independent predictors of high SYNTAX score. The survival analysis showed that long-term revascularization rates were comparable between the GGT groups (for 36 U/l cut point) of the overall population (7.7% vs 8.6% logrank, p = 0.577), whereas long-term all cause mortality rate was higher in the GGT ≥ 36 U/l group (3.6% vs 11.6% logrank, p = 0.001). In Cox proportional hazards regression model, GGT ≥ 36 U/l group was found to be an independent predictor of long-term all cause mortality in the unadjusted (HR 2.54, 95% CI 1.17–5.48, p = 0.018) and age- and gender-adjusted (HR 2.58, 95% CI 1.19–5.58, p = 0.016) models.ConclusionSerum GGT level was independently associated with coronary complexity and long-term mortality in patients with stable coronary artery disease.     

Atrial fibrillation and acute myocardial infarction: antithrombotic therapy and outcomes

BackgroundAtrial fibrillation guidelines recommend long-term use of warfarin according to a patient's predicted risk of stroke. After acute myocardial infarction, however, combining warfarin and antiplatelet medications poses challenges.MethodsBy using data from more than 69,255 patients with acute myocardial infarction who were enrolled in the National Cardiovascular Data Registry's Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines at 309 hospitals from July 1, 2008, to September 30, 2009, we describe the characteristics and outcomes of the population with myocardial infarction with atrial fibrillation diagnosed within 2 weeks before index myocardial infarction admission (7.1%, N = 4947). Use of discharge antithrombotic therapy is described overall and across levels of predicted stroke and bleeding risks.ResultsCompared with patients without atrial fibrillation, those with atrial fibrillation before their index myocardial infarction were older and had more comorbidities and worse in-hospital outcomes. Only 32.5% of patients with atrial fibrillation were taking warfarin before their myocardial infarction admission. In these patients, use of warfarin at discharge increased with higher Congestive heart failure, Hypertension, Age, Diabetes, Stroke [Doubled] (CHADS₂) risk strata (28.5%, 34.6%, and 43.5% for CHADS₂ scores 0, 1, and ≥2; P < .001) and increased in patients at low, intermediate, and high risk of bleeding (25.4%, 42.3%, and 42.1%; P = .004). Triple therapy at discharge (aspirin plus clopidogrel plus warfarin) was used in a minority of this population (14.6%).ConclusionsUse of warfarin at discharge in patients with atrial fibrillation is greater among those with higher stroke and bleeding risks, but despite higher-risk profiles, less than half received warfarin at discharge. These findings highlight that clarification is needed to guide choice of antithrombotic therapy for patients with both atrial fibrillation and acute myocardial infarction.     

D-dimer levels in assessing severity and clinical outcome in patients with community-acquired pneumonia. A secondary analysis of a randomised clinical trial

BackgroundD-dimer levels are in several studies elevated in patients with CAP. In this study we assess the use of D-dimer levels and its association with severity assessment and clinical outcome in patients hospitalised with community-acquired pneumonia.MethodsIn a subset of randomised trial patients with community-acquired pneumonia serial D-dimer levels was analysed. CURB-65 scores were calculated at admission.ResultsA total of 147 patients were included. D-dimer levels at admission were higher in patients with severe CAP (2166 ± 1258 versus1630 ± 1197 μg/l, p = 0.03), with clinical failure at day 30 (2228 ± 1512 versus 1594 ± 1078 μg/l, p = 0.02) and with early failure (2499 ± 1817 μg/l versus 1669 ± 1121 μg/l, p = 0.01). Non-survivors had higher D-dimer levels (3025 ± 2105 versus 1680 ± 1128 μg/l, p = 0.05). None of the 16 patients with D-dimer levels < 500 μg/l died. In multivariate analysis D-dimer levels were not associated with clinical outcome. D-dimer levels have poor accuracy for predicting clinical outcome at day 30 (AUC 0.62, 95% CI 0.51–0.73) or 30 day mortality (AUC 0.71 (95% CI 0.51–0.91)). Addition of D-dimer levels to CURB-65 did not increase accuracy. No differences were observed in serial D-dimer levels between patients with clinical success or failure at day 30.ConclusionD-dimer levels are elevated in patients with CAP. Significantly higher D-dimer levels are found in patients with clinical failure and with severe CAP. D-dimer levels as single biomarker or as addition to the CURB-65 have no added value for predicting clinical outcome or mortality. D-dimer levels < 500 μg/l may identify candidates at low risk for complications.     

The L-Arginine–Asymmetric Dimethylarginine Ratio is an Independent Predictor of Mortality in Dilated Cardiomyopathy

BackgroundAsymmetric dimethylarginine (ADMA) is associated with increased mortality in patients with chronic heart failure but it remains unclear if the etiology of heart failure influences the prognostic value of dimethylarginines.Methods and ResultsL-Arginine, ADMA, and symmetric dimethylarginine (SDMA) were measured by liquid chromatography–tandem mass spectrometry in 341 patients with chronic heart failure due to dilated cardiomyopathy (DCM; n = 226) or ischemic cardiomyopathy (ICM; n = 115). Median (interquartile range [IQR]) ADMA and SDMA plasma levels were higher, L-arginine and the L-arginine–ADMA ratio were lower in patients with severe forms of heart failure (New York Heart Association (NYHA) functional class III or IV) compared with milder forms (NYHA functional class I or II) (ADMA 0.57 (0.14) μmol/L vs 0.54 (0.12) μmol/L [P < .001]; SDMA 0.47 (0.27) μmol/L vs 0.37 (0.13) μmol/L [P < .001]; L-arginine 81.8 (39.1) μmol/L vs 92.6 (39.3) μmol/L [P < .01]), but no significant differences were observed between the different etiologies. The L-arginine–ADMA ratio was associated with outcome only in patients with DCM. In multivariate analysis, the mortality risk of DCM patients was significantly lower for those in the highest quartile compared with the lowest quartile during a median observation time of 3.3 years (hazard ratio 0.31, 95% CI 0.11–0.88; P = .028, adjusted for other risk factors).ConclusionsDCM patients with unfavourable L-arginine–ADMA ratio are at increased risk for death.     

Vascular disease and stroke risk in atrial fibrillation: a nationwide cohort study

BackgroundVascular disease (including myocardial infarction and peripheral artery disease) has been proposed as a less well-validated risk factor for stroke in patients with atrial fibrillation. We investigated whether vascular disease is an independent risk factor of stroke/thromboembolism in atrial fibrillation and whether adding vascular disease improves Congestive heart failure, Hypertension, Age 75 years, Diabetes, previous Stroke (CHADS₂) risk stratification.MethodsBy using nationwide Danish registers, we identified all patients discharged with atrial fibrillation and not treated with vitamin K antagonist or heparin between 1997 and 2008. The rate of stroke/thromboembolism in patients with atrial fibrillation with and without vascular disease was determined, and the risk associated with vascular disease was estimated in Cox regression analyses. The value of adding vascular disease to the CHADS₂ score was evaluated by Net Reclassification Improvement and Integrated Discrimination Improvement.ResultsWe included 87,202 patients with non-valvular atrial fibrillation; of these, 15,212 (17.4%) had vascular disease, 11,750 (77.2%) had myocardial infarction, 2503 (16.5%) had peripheral artery disease, and 959 (6.3%) had both. In patients with a CHADS₂ score = 0, the rate of stroke/thromboembolism at 1-year follow-up was 2.31 (1.63-3.26) and 1.52 (1.34-1.73) per 100 person-years in patients with and without vascular disease, respectively. Vascular disease increased the risk of stroke/thromboembolism in both univariate (hazard ratio [HR] 1.26; confidence interval [CI], 1.18-1.35) and multivariate (HR, 1.12; CI, 1.05-1.21) analyses. The risk of stroke/thromboembolism associated with peripheral artery disease alone (HR, 1.93; CI, 1.70-2.19) was greater than the risk with myocardial infarction alone (HR, 1.12; CI, 1.04-1.21), and vascular disease significantly improved the predictive ability of the CHADS₂ score (Net Reclassification Improvement 0.032, P < .001).ConclusionsVascular disease is an independent predictor of stroke/thromboembolism in atrial fibrillation and improves the predictive ability of the CHADS₂ score.     

The coexistence of heart failure predicts short term mortality, but not disability, in patients with acute ischemic stroke treated with thrombolysis: The Florence area Registry

BackgroundThrombolysis in ischemic stroke reduces disability but not mortality. Our aim was to evaluate the predictivity of heart failure (HF) diagnosis on 90-day mortality and disability in stroke patients undergoing thrombolysis.Material and methodsHospital records of all consecutive stroke patients treated with thrombolysis at our University Hospital were reviewed. Clinical assessment for HF and echocardiogram were available for all patients according to the thrombolysis institutional protocol. History of HF, LVEF < 40%, or BOSTON score ≥ 5 were tested as predictors.ResultsOf 130 patients (age 66 ± 14 years, 64.6% males, baseline NIHSS 15.6 ± 8.8), 17 (13.1%) had a history of HF, 16 (12.7%) a BOSTON score ≥ 5, 13 (10.9%) a LVEF < 40% and 24 (19.0%) met clinical criteria for HF diagnosis. Ninety-day mortality and incidence of disability were 16.1% and 36.1%, respectively. After adjustment for age, sex, baseline stroke severity and pre-stroke disability, LVEF < 40% and clinical diagnosis of HF were predictors of 90-day mortality, (p = 0.007 and p = 0.037, respectively).ConclusionClinical diagnosis of HF predicts mortality, but not disability, in acute stroke patients undergoing thrombolysis. Unlike anamnestic record of HF, clinical evaluation of cardiac function, with estimation of LVEF, predicts mortality.     

Asymmetric dimethylarginine as a prognostic marker for cardiovascular complications in hypertensive patients

Hypertension has a serious harmful effect on the physiological and biochemical functions of heart that end with the appearance of cardio-vascular diseases. Asymmetric dimethylarginine (ADMA) has evolved as an important regulator of nitric oxide (NO) synthesis. The relationship between ADMA and essential hypertension has been scarcely explored. This study is aiming to investigate the physiological, pathological, and biochemical roles of plasma ADMA in relation to serum nitric oxide and also the relation between ADMA and NO with other traditional cardiovascular risk factors in hypertensive patients.MethodsThe study was designed as a prospective case-control study which included 60 hypertensive cardiovascular patients and 10 healthy volunteers as a control group. The patients were divided into four groups: hypertension with cardiovascular complications, uncontrolled hypertension (blood pressure >139/89), controlled hypertension, and control group. Levels of ADMA and nitric oxide were assessed and statistically correlated to other clinical and laboratory values [cholesterol, triglycerides, urea, creatinine, and fasting and postprandial blood sugar].ResultsThe plasma ADMA level in group I was significantly increased (2.29 ± 0.06 μmol/L) compared to control group (0.55 ± 0.05 μmol/L) P = 0.001 and also serum NO level was significantly decreased in this group (11.65 ± 0.75 μmol/L) compared to control group (52.11 ± 1.43 μmol/L) P = 0.001. This group had variable complications, e.g., ischemic heart disease, pulmonary hypertension, pulmonary embolism, and cerebrovascular disease. Group II: plasma ADMA level was significantly increased in this group (1.41 ± 0.06) and also serum NO level was significantly decreased (30.91 ± 1.31) compared to control group (P = 0.001). Group III: they had a lower plasma level of ADMA (1.11 ± 0.05) compared to groups I and II (P value: 0.001) and significantly higher than the control group. The serum NO level was significantly decreased (40.01 ± 0.67) compared to control group and significantly higher than groups I and II. Hypertensive groups I, II, and III showed a significant increase in mean fasting and postprandial blood sugar (171.4 ± 71.00, 143.64 ± 37.00, and 137.00 ± 27.06 mg/dl, respectively) compared to control group (85.32 ± 13.17 mg/dl). Urea, creatinine, cholesterol, and triglycerides in the hypertensive groups (I, II, and III) showed a significant increase compared to control group with significant positive correlation in relation to ADMA.ConclusionsADMA is elevated in hypertensive patients. Elevated ADMA concentrations are associated with impaired endothelium functions, which are demonstrated by NO reduction in the sera of hypertensive patients. ADMA is correlated positively with the traditional cardiovascular risk factors. Also there was a strong significant negative correlation between NO and ADMA levels in the whole hypertensive groups.     

Impacto pronóstico de la enfermedad renal crónica sobre el cierre percutáneo de la orejuela izquierda en la fibrilación auricular: una experiencia unicéntrica

BackgroundPercutaneous left atrial appendage closure (LAAC) has been proposed as an alternative to anticoagulation therapy in patients with nonvalvular atrial fibrillation to decrease the thromboembolic risk, while avoiding the risks of chronic anticoagulation. This option may be attractive in patients with nonvalvular atrial fibrillation and chronic kidney disease (CKD), since they exhibit both high-thromboembolic and bleeding risks.ObjectiveTo evaluate the prognostic impact of the presence of CKD in patients with atrial fibrillation undergoing LAAC peri-procedure and during the follow-up as compared with patients with preserved renal function.MethodsRetrospective, observational study that included 124 consecutive patients with atrial fibrillation undergoing LAAC in a university hospital, and the results were evaluated according to the baseline renal function of the patients.ResultsThe median age was 75.5 years (IQR 67.6–80) and 62.1% were men, the median of CHA₂DS₂-Vasc and HASBLED scores was 4 (IQR 3–4) for both scores. Up to 57.3% of the total sample had CKD. Baseline characteristics were similar between groups, but CKD patients were older and had a higher HASBLED score. During the procedure, no thromboembolic, bleeding events, or deaths were observed. Combining the time of hospitalization and follow-up, no significant differences were observed between groups in the annual rate of thromboembolic events (0.97/100 patient-years [100PY] vs. 4.06/100PY, p = .09), but there was a higher rate of bleeding events (5.67/100PY vs. 13.3/100PY, p = .033) and mortality among CKD patients (6.50/100PY vs. 17.2/100PY, p = .009), with an odds ratio of 2.711 (95% CI 1.96–6.95). In the multivariate analysis, a preserved eGFR was independently associated with a lower mortality risk.ConclusionsLAAC is a valid alternative to oral anticoagulation in patients with CKD and atrial fibrillation, with a low-rate of peri- and post-procedure complications, although CKD patients exhibited a higher risk of bleeding and mortality during the follow-up. However, these higher rates may not be necessarily related to the procedure.     

Low ankle-brachial index predicts early risk of recurrent stroke in patients with acute cerebral ischemia

ObjectiveLow Ankle-Brachial Blood Pressure Index (ABI) identifies patients with symptomatic and asymptomatic peripheral arterial disease (PAD). We sought to investigate the association of low ABI with early risk of stroke recurrence in patients with acute cerebral ischemia (ACI) and without history of symptomatic PAD.MethodsConsecutive patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) and no previous history of PAD were prospectively evaluated with ABI measurements. Demographic characteristics, vascular risk factors and secondary prevention therapies were documented. An ABI ≤0.90 in either leg was considered as evidence of asymptomatic PAD, and an ABI >0.90 was considered as normal. Patients with elevated ABI (>1.30) were excluded. The outcome of interest was recurrent stroke during 30-day follow-up.ResultsA total of 176 patients with acute cerebral ischemia (mean age 64 ± 14 years, 59.1% men, 76.7% AIS) were evaluated. Asymptomatic PAD was detected in 14.8% (95%CI: 10.2–20.8%) of the studied population. The following factors were independently associated with low ABI on multivariate logistic regression models, after adjustment for potential confounders: coronary artery disease (p = 0.008), diabetes mellitus (p = 0.017) and increasing age (p = 0.042). The cumulative 30-day recurrence rate was higher in patients with low ABI (19.2%; 95%CI: 4.1–34.3) compared to the rest (3.3%; 95%CI: 0.4–6.2%; p = 0.001). Atherothrombotic stroke (ASCO grade I; p < 0.001), increasing age (p = 0.002) and low ABI (p = 0.004) were independent predictors of stroke recurrence on multivariate Cox regression models adjusting for confounders.ConclusionsLow ABI appears to be associated with a higher risk of early recurrent stroke in patients with ACI and no history of symptomatic PAD.     

Low cardiovascular event rate and high atrial fibrillation recurrence rate one year after electrical cardioversion

BackgroundElectrical cardioversion is widely used to restore sinus rhythm in patients with atrial fibrillation. However, the long term clinical event and sinus rhythm maintenance rates following electrical cardioversion still remains unclear. This study evaluated one year incidence and risk factors for cardiovascular events and atrial fibrillation recurrence in a single center clinical practice.MethodsIn a prospective study 188 patients with atrial fibrillation who underwent electrical cardioversion were enrolled. Patients and their primary care physicians were followed up one year after cardioversion and patient clinical and arrhythmic event rate was evaluated. Data obtained from patients and general practitioners were combined and the results were analyzed with PSPP 0.8.5 software.ResultsElectrical cardioversion success rate was 90.4%. Within a year after cardioversion one patient (0.6%) suffered myocardial infarction, three patients (1.9%) had a stroke/transitory ischemic attack (TIA), three patients (1.6%) died and three patients (1.9%) had a bleeding event that required hospitalization. The presence of diabetes mellitus was the only factor with a tendency to increase the risk of combined event of myocardial infarction, stroke/TIA and bleeding (P = 0.096). At follow up 30.0% of patients reported having atrial fibrillation and within a year 62.2% had suffered at least one atrial fibrillation paroxysm. The proportion of patients who underwent additional cardioversions after the initial hospitalization was 32.5%. The factors that significantly increased the risk of atrial fibrillation recurrence were history of stroke/TIA (P = 0.014) and increased left atrial volume index on echocardiography (P = 0.039). Greater left atrial diameter had a tendency toward an increased risk (P = 0.087).ConclusionsCardiovascular event rate one year after electrical cardioversion was low. Electrical cardioversion had a high immediate success rate, however, maintenance of stable sinus rhythm in the long term was low.     

Type 2 diabetes mellitus and chronic hepatitis C: Which is worse? Results of a long-term retrospective cohort study

BackgroundThe long-term outcome in patients with chronic hepatitis C and type 2 diabetes mellitus treated with interferon and ribavirin is unclear. We compared incidence of liver-related events and mortality rates between hepatitis C virus-positive patients with or without diabetes mellitus, and the incidence of diabetes-related events between diabetic patients with and without hepatitis C.MethodsRetrospective study of 309 patients with chronic hepatitis C. Incidence of liver-related events, diabetes-related events and mortality rates were assessed over a mean follow-up of 11.02 ± 4.9 years.Results50 (16%) chronic hepatitis C patients had diabetes mellitus. Diabetics showed a higher number of diabetes- and liver-related events than non-diabetics (10% vs 1.5%, p = 0.006; 18% vs 5.7%, p = 0.007, respectively) with a mortality of 14% vs 1.5% (p = 0.0003). Baseline cirrhosis (p = 0.002) and non-sustained virological response (p = 0.01) were independent risk factors for liver events; diabetes mellitus (p = 0.01) and hypertension (p = 0.0017) were independent factors for diabetes-related events.ConclusionsIn patients with chronic hepatitis C, comorbidity with diabetes mellitus was associated with a higher mortality rate and incidence of liver/diabetes-related events. Independent risk factors for liver-related events were the non-response to antiviral therapy and cirrhosis at baseline.     

Different prognostic value of white blood cell subtypes in patients with acute cerebral infarction

ObjectiveWe aimed to investigate the relationship of each white blood cells (WBC) subtype with neurologic severity and outcome in acute stroke.MethodsWe included 779 patients with first-ever acute cerebral infarction within 72 h after symptom onset. We investigated the association between counts for WBC subtypes in peripheral blood at admission and (1) initial stroke severity; (2) early change in stroke severity within one week; and (3) functional outcome at three months.ResultsHigher total WBC and neutrophil counts were associated with more severe stroke at admission (p < 0.001). In contrast, lower lymphocyte counts were associated with a lesser improvement during the first week after admission (p < 0.05) and with poor functional outcome at three months (OR = 0.706 per 1000 lymphocyte counts/mm³, p = 0.020).ConclusionsOur study merits further investigation on the role of each WBC subtype in ischemic injury and different prognostic value of WBC subtypes measured at admission in acute stroke.     

Outcomes of contemporary management of gangrenous and non-gangrenous acute cholecystitis

BackgroundGangrenous cholecystitis (GC) is considered a more severe form of acute cholecystitis. The risk factors associated with this condition and its impact on morbidity and mortality compared with those of non-gangrenous acute cholecystitis (NGAC) are poorly defined and based largely on findings from older studies.MethodsPatients with histologically confirmed acute cholecystitis treated in specialized units in a tertiary hospital between 2005 and 2010 were identified from a prospectively maintained database. Data were reviewed retrospectively and patients with GC were compared with those with NGAC.ResultsA total of 184 patients with NGAC and 106 with GC were identified. The risk factors associated with GC included older age (69 years vs. 57 years; P= 0.001), diabetes (19% vs. 10%; P= 0.049), temperature of >38 °C (36% vs. 16%; P < 0.001), tachycardia (31% vs. 15%; P= 0.002), detection of muscle rigidity on examination (27% vs. 12%; P= 0.01) and greater elevations in white cell count (WCC) (13.4 × 10⁹/l vs. 10.7 × 10⁹/l; P < 0.001), C-reactive protein (CRP) (94 mg/l vs. 17 mg/l; P= 0.001), bilirubin (19 µmol/l vs. 17 µmol/l; P= 0.029), urea (5.3 mmol/l vs. 4.7 mmol/l; P= 0.016) and creatinine (82 µmol/l vs. 74 µmol/l; P= 0.001). The time from admission to operation in days was greater in the GC group (median = 1 day, range: 0–14 days vs. median = 1 day, range: 0–10 days; P= 0.029). There was no overall difference in complication rates between the GC and NGAC groups (22% vs. 14%; P= 0.102). There was a lower incidence of common bile duct stones in the GC group (5% vs. 13%; P= 0.017). Gangrenous cholecystitis was associated with increased mortality (4% vs. 0%; P= 0.017), but this was not an independent risk factor on multivariate analysis.ConclusionsGangrenous cholecystitis has certain clinical features and associated laboratory findings that may help to differentiate it from NGAC. It is not associated with an overall increase in complications when treated in a specialized unit.Case series which identifies patients at risk of having gangrenous cholecystitis when presenting with acute gallstone disease     

Colorectal stenting as a bridge to surgery reduces morbidity and mortality in left-sided malignant obstruction: a predictive risk score-based comparative study

BackgroundThe Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity model, and its Portsmouth and colorectal modifications are used to predict postoperative mortality and morbidity after colorectal surgery.AimsTo compare stent placement as a bridge to surgery vs. emergency surgical resection in patients with acute left-sided colorectal cancer obstruction using P-POSSUM and CR-POSSUM.MethodsFrom January 2008 to December 2009, the physiological and operative scores, morbidity and mortality predicted by the P-POSSUM and CR-POSSUM scores were collected in all consecutive patients with LCCO who underwent surgical resection directly (Group A) or after stent placement (Group B).ResultsEighty-six patients were enrolled (Group A-41 and Group B-45). The observed 30-day mortality rate was 9.8% (4/41) in Group A and 2.4% (1/45) in Group B. The 30-day morbidity rate was 61% (25/41) in Group A and 29% (13/45) in Group B. The mean values of P-POSSUM morbidity (A = 70.5% vs. B = 34.3%; p = 0.001), P-POSSUM mortality (A = 13.6% vs. B = 2.4%; p = 0.001) and CR-POSSUM mortality (A = 15.1% vs. B = 4.9%; p = 0.001) were significantly lower in the Group B patients than in the Group A patients.ConclusionsBridge to surgery strategy reduces the surgical risks in LCCO, and P-POSSUM and CR-POSSUM scores represent a good tool for comparing the two strategies.     

Unchanged plasma levels of dimethylarginines and nitric oxide in chronic hepatitis C

Objective. Previous studies have shown that asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and nitric oxide (NO) play a prominent role in liver dysfunction. The objective of this study was to determine whether plasma levels of ADMA, SDMA and NO are altered in patients with chronic hepatitis C. Material and methods. Plasma levels of ADMA, SDMA and NO (nitrite plus nitrate) were measured in 22 patients with chronic hepatitis C and 24 patients with sustained virologic response after treatment with peginterferon plus ribavirin. Seven healthy volunteers served as controls. Results. Plasma levels of ADMA, SDMA and NO were not significantly different between groups: chronic hepatitis C, ADMA 0.55±0.06, SDMA 0.22±0.03, NO 36.3±5.9 µmol/l; treated patients, ADMA 0.60±0.15, SDMA 0.31±0.05, NO 36.1±5.5 µmol/l; controls, ADMA 0.65±0.08, SDMA 0.28±0.05, NO 40.7±8.9 µmol/l). Conclusions. Our results show that plasma NO, ADMA and SDMA concentrations are not changed in patients with chronic hepatitis C without superimposed signs of acute inflammatory activity. Furthermore, no significant differences in plasma values of NO and dimethylarginines were observed between the group of untreated patients and the group of patients treated with interferon plus ribavirin