Perioperative SBP changes during orthopedic surgery in the elderly: clinical implications.

OBJECTIVES: We aimed to determine SBP changes during the perioperative period of a scheduled knee surgery under regional anesthesia and the extent of perioperative (in-hospital) white-coat effect. METHODS: All patients (aged ≥60 years) underwent clinic SBP measurements during both cardiological and anesthesiological visits, while home SBP the week before admission was obtained. Clinic SBP was registered just before surgery, during surgery and reanimation. Ambulatory monitoring was also performed (12 h before surgery to 6-8 h after surgery). One month after discharge, clinic SBP was measured at hypertension unit. RESULTS: Eligible participants (N = 50, mean age 74 ±â€Š7 years, 34% men, 26% with history of cardiovascular disease) had higher SBP during the anesthesiologic than the cardiological evaluation (157 ±â€Š23 vs. 144 ±â€Š18 mmHg, P < 0.001), and the former levels were almost identical to those clinically measured just before surgery. A significant white-coat effect between ambulatory and clinic measurements just before surgery (16.4 ±â€Š21 mmHg, P < 0.001) and between entire ambulatory recording and clinic BP measurements the day before surgery (12.4 ±â€Š16 and 24.8 ±â€Š21 mmHg for cardiologic and anesthesiologic visit, respectively, P < 0.001 for both) was noticed, whereas intraoperatively the white-coat effect faded away. There was a greater SBP decline during surgery in patients aged more than 75 years compared with younger, whereas selective treatment discontinuation (except beta blockers and calcium channel blockers) did not modulate SBP trajectories. CONCLUSION: The significant white-coat effect observed in scheduled noncardiac surgery is clinically important and the home BP measurement performed before surgery or ABPM, highly reflects the hypertensive burden of the patient. Blood pressure decrease during surgery is quite pronounced especially in patients aged more than 75 years. Aggressive BP lowering should be avoided.

Effects of metabolic syndrome on arterial function in different age groups: the Advanced Approach to Arterial Stiffness study.

OBJECTIVE: The aim of the Advanced Approach to Arterial Stiffness study was to compare arterial stiffness measured simultaneously with two different methods in different age groups of middle-aged and older adults with or without metabolic syndrome (MetS). The specific effects of the different MetS components on arterial stiffness were also studied. METHODS: This prospective, multicentre, international study included 2224 patients aged 40 years and older, 1664 with and 560 without MetS. Patients were enrolled in 32 centres from 18 European countries affiliated to the International Society of Vascular Health & Aging. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI) and the carotid-femoral pulse wave velocity (CF-PWV) in four prespecified age groups: 40-49, 50-59, 60-74, 75-90 years. In this report, we present the baseline data of this study. RESULTS: Both CF-PWV and CAVI increased with age, with a higher correlation coefficient for CAVI (comparison of coefficients P < 0.001). Age-adjusted and sex-adjusted values of CF-PWV and CAVI were weakly intercorrelated (r = 0.06, P < 0.001). Age-adjusted and sex-adjusted values for CF-PWV but not CAVI were higher in presence of MetS (CF-PWV: 9.57 ±â€Š0.06 vs. 8.65 ±â€Š0.10, P < 0.001; CAVI: 8.34 ±â€Š0.03 vs. 8.29 ±â€Š0.04, P = 0.40; mean ±â€ŠSEM; MetS vs. no MetS). The absence of an overall effect of MetS on CAVI was related to the heterogeneous effects of the components of MetS on this parameter: CAVI was positively associated with the high glycaemia and high blood pressure components, whereas lacked significant associations with the HDL and triglycerides components while exhibiting a negative association with the overweight component. In contrast, all five MetS components showed positive associations with CF-PWV. CONCLUSION: This large European multicentre study reveals a differential impact of MetS and age on CAVI and CF-PWV and suggests that age may have a more pronounced effect on CAVI, whereas MetS increases CF-PWV but not CAVI. This important finding may be due to heterogeneous effects of MetS components on CAVI. The clinical significance of these original results will be assessed during the longitudinal phase of the study.

The optimal night-time home blood pressure monitoring schedule: agreement with ambulatory blood pressure and association with organ damage.

OBJECTIVE: Night-time home blood pressure (HBP) monitoring has emerged as a feasible, reliable and low-cost alternative to ambulatory blood pressure (ABP) monitoring. This study evaluated the optimal schedule of night-time HBP monitoring in terms of agreement with night-time ABP and association with preclinical target-organ damage. METHODS: Untreated hypertensive adults were evaluated with ABP (24-h) and HBP monitoring (daytime: six days, duplicate morning and evening measurements; night-time: three nights, three-hourly automated measurements/night), and determination of left ventricular mass index, common carotid intima-media thickness and urinary albumin excretion. RESULTS: A total of 94 patients with all nine night-time HBP measurements were analysed [mean age 51.8 ±â€Š11.1 (SD) years, men 57%). By averaging an increasing number of night-time systolic HBP readings, there was a consistent trend towards stronger association of night-time HBP with night-time ABP (correlation coefficients r increased from 0.69 to 0.81), and with target-organ damage indices (for left ventricular mass index r increased from 0.13 to 0.22, carotid intima-media thickness 0.12-0.25, urinary albumin excretion 0.33-0.41). However, no further improvement in the association was observed by averaging more than four to six night-time readings. The diagnostic agreement between HBP and ABP in detecting nondippers was improved by averaging more readings, with a plateau at four readings (single reading: agreement 81%, kappa 0.37; four readings: 88%, 0.49; nine readings: 84%, 0.40). CONCLUSION: A two-night HBP schedule (six readings) appears to be the minimum requirement for a reliable assessment of night-time HBP, which gives reasonable agreement with ABP and association with preclinical organ damage.

Thermal ablation may improve outcomes in patients with colorectal liver metastasis: a case-control study.

PURPOSE: Local thermal ablation may extend the scope of palliative therapy in patients with colorectal liver metastasis. We performed a retrospective, case-controlled study to compare patients with colorectal liver metastases that were treated with percutaneous radiofrequency (RF) or microwave (MW) thermal ablation, against the control group of chemotherapy alone. METHODS: We described baseline demographics, ablation sessions, procedure duration and related complications. We compared outcomes of percutaneous thermal ablation versus chemotherapy alone (controls) in patients with colorectal liver metastasis. The control group assigned (non-ablated patients) had similar demographics and prior treatment profile when compared to ablated patients. Progression-free survival (PFS) and overall survival (OS) were estimated for the two groups. RESULTS: Twenty-eight cases with 57 baseline hepatic lesions (median age 68 years; male to female ratio 2:1) were evaluated and compared with 48 controls. A total of 55 sessions (52 RF, 3 MW) were performed among the cases, with minimal procedural time (median 8 min), zero mortality and no severe complications (3 cases of local hepatic hematoma not requiring hospitalization). Ablated patients had prolonged median PFS (19.4 months) and OS (27.5 months) when compared against controls (14.0 and 21.4 months, respectively). After adjusting for hepatic involvement, PFS estimates were comparable and OS was better for the ablated group. One and 2-year survival estimates were 0.96 and 0.79 for thermal ablation patients compared with 0.82 and 0.52 for controls (p=0.05 and p=0.07, respectively). CONCLUSION: Percutaneous thermal ablation may delay progression and death in colorectal cancer patients with metastatic liver disease.

Methodology and technology for peripheral and central blood pressure and blood pressure variability measurement: current status and future directions - Position statement of the European Society of Hypertension Working Group on blood pressure monitoring and cardiovascular variability.

Office blood pressure measurement has been the basis for hypertension evaluation for almost a century. However, the evaluation of blood pressure out of the office using ambulatory or self-home monitoring is now strongly recommended for the accurate diagnosis in many, if not all, cases with suspected hypertension. Moreover, there is evidence that the variability of blood pressure might offer prognostic information that is independent of the average blood pressure level. Recently, advancement in technology has provided noninvasive evaluation of central (aortic) blood pressure, which might have attributes that are additive to the conventional brachial blood pressure measurement. This position statement, developed by international experts, deals with key research and practical issues in regard to peripheral blood pressure measurement (office, home, and ambulatory), blood pressure variability, and central blood pressure measurement. The objective is to present current achievements, identify gaps in knowledge and issues concerning clinical application, and present relevant research questions and directions to investigators and manufacturers for future research and development (primary goal).

Expert consensus on the rational clinical use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

Two proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, evolocumab and alirocumab, have recently been approved by both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of hypercholesterolemia. These fully human monoclonal antibodies selectively block PCSK9, thus permitting the low-density lipoprotein (LDL) receptor to effectively recycle to the surface of liver cells. The administration of these antibodies leads to robust LDL cholesterol (LDL-C) lowering by 50-60% on top of maximum hypolipidemic treatment. At least 4 randomized, placebo-controlled studies are under way and will address the question of whether the administration of these PCSK9 inhibitors is associated with a significant reduction of cardiovascular events. Because of the high cost associated with the use of these medications it is very important to consider which patients may gain the most benefit, at least until the results of outcome studies are available. In this Consensus paper, 34 clinicians/scientists define 3 groups of patients that should be currently considered as candidates for the use of these novel drugs. These include: 1a. Adults with established cardiovascular disease and LDL-C≥100 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe, 1b. Adults with diabetes and established cardiovascular disease or chronic kidney disease or target organ damage and LDL-C ≥100 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe, 2. Adults with familial hypercholesterolemia (FH) without established cardiovascular disease and LDL-C ≥130 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe (evolocumab is also indicated in children above 12 years with homozygous FH), and 3. Adults at high or very high cardiovascular risk who are statin intolerant and have an LDL-C ≥100 and ≥130 mg/dL, respectively, while on any tolerated hypolipidemic treatment.

Night-time home versus ambulatory blood pressure in determining target organ damage.

OBJECTIVE: This study aimed to evaluate the association of night-time blood pressure (BP) assessed by home blood pressure (HBP) or ambulatory blood pressure (ABP) monitoring with preclinical target organ damage in untreated hypertension. METHODS: Untreated hypertensive study participants were evaluated with ABP monitoring (24-h) and HBP monitoring during daytime (6 days, duplicate morning and evening measurements) and night-time (automated asleep measurements, three nights, 3-hourly measurements/night). Target organ damage was assessed by echocardiographic left ventricular mass index (LVMI), common carotid intima-media thickness (cIMT), urine albumin excretion (UAE), and ankle-brachial index (ABI). RESULTS: A total of 131 study participants were analysed [mean age 52.1 ±â€Š11.9 (SD) years, BMI 29.9 ±â€Š5.3  kg/m2, men 58%, cardiovascular disease history 6.1%]. Daytime and night-time HBP were slightly higher than the respective ABP values (mean difference for systolic daytime/night-time 3.5 ±â€Š10.6/2.6 ±â€Š9.8  mmHg, P < 0.01 for both comparisons and diastolic -0.3 ±â€Š6.8/1.2 ±â€Š6.2  mmHg, P = NS/0.02, respectively). There was a strong correlation between daytime ABP and HBP (r = 0.71/0.72, systolic/diastolic), as well as between the respective night-time values (r = 0.80/0.79; all P < 0.01). Night-time ABP and HBP presented strong and comparable correlations with all the indices of preclinical target organ damage. In multivariate analyses, both LVMI (R2 = 0.26) and cIMT (R2 = 0.25) were determined by night-time systolic HBP, age and male sex; UAE (R2 = 0.28) by night-time systolic HBP and male sex; ABI (R2 = 0.20) by male sex and night-time home pulse pressure. CONCLUSION: In untreated hypertensives, night-time BP assessed by home monitoring appears to be as good as night-time ambulatory monitoring in determining preclinical target organ damage.

The diverse roles of adiponectin in non-small-cell lung cancer: current data and future perspectives.

In recent years, there is growing research interest for the biological role of adipose tissue-derived bioactive factors, mainly including adipokines, in various forms of cancer. Adiponectin (APN) is the most abundant circulating adipokine, and a key mediator of several cancer-related processes, such as cell proliferation, apoptosis, regulation of tumor cell invasion and angiogenesis. In this review we summarize and critically discuss the published literature on the diverse roles of APN in non-small-cell lung cancer, including its implication in lung cancer development, its use as a diagnostic and prognostic biomarker, and its correlation with cancer-related cachexia. The main challenges and future perspectives, mainly with regard to the potential development of APN-targeted therapeutic agents in cancer therapeutics, are also briefly presented and discussed.

Cost estimation of hypertension management based on home blood pressure monitoring alone or combined office and ambulatory blood pressure measurements.

This study aims at estimating the resources consumed and subsequent costs for hypertension management, using home blood pressure (BP) monitoring (HBPM) alone versus combined clinic measurements and ambulatory blood pressure monitoring (C/ABPM). One hundred sixteen untreated hypertensive subjects were randomized to use HBPM or C/ABPM for antihypertensive treatment initiation and titration. Health resources utilized within 12-months follow-up, their respective costs, and hypertension control were assessed. The total cost of the first year of hypertension management was lower in HBPM than C/ABPM arm (€1336.0 vs. €1473.5 per subject, respectively; P < .001). Laboratory tests' cost was identical in both arms. There was no difference in achieved BP control and drug expenditure (HBPM: €233.1 per subject; C/ABPM: €247.6 per subject; P = not significant), whereas the cost of BP measurements and/or visits was higher in C/ABPM arm (€393.9 vs. €516.9, per patient, respectively P < .001). The cost for subsequent years (>1) was €348.9 and €440.2 per subject, respectively for HBPM and C/ABPM arm and €2731.4 versus €3234.3 per subject, respectively (P < .001) for a 5-year projection. HBPM used alone for the first year of hypertension management presents lower cost than C/ABPM, and the same trend is observed in 5-year projection. The results on the resources consumption can be used to make cost estimates for other health-care systems.

Left-ventricular hypertrophy is associated better with 24-h aortic pressure than 24-h brachial pressure in hypertensive patients: the SAFAR study.

OBJECTIVE: To test the hypothesis that left-ventricular hypertrophy (LVH) is better associated with aortic, than brachial, 24-h average blood pressure (BP) in individuals with hypertension. BACKGROUND: The office aortic BP is associated better with organ damage, such as LVH, than the office brachial BP; whether the 24-h average aortic BP associates better with LVH, than the 24-h average brachial BP, has never been tested. METHODS: Aortic ambulatory BP monitoring (ABPM) was performed with a novel validated oscillometric cuff-based BP recording device, also used for simultaneous brachial ABPM, and the application of pulse wave analysis method. Office brachial and aortic BP were assessed with validated oscillometric recording device and pulse wave analysis, respectively; left-ventricular mass was measured by ultrasound. RESULTS: Regression analysis performed in 229 individuals (aged 54.3 ±â€Š14.6 years; 56% men; 75% hypertensive patients) showed that the 24-h average aortic SBP was significantly better associated with left-ventricular mass index and LVH than the 24-h average brachial, as well as, office (brachial or aortic) SBP, independently of age, sex, obesity or treatment. Receiver operator characteristics curve analysis showed a higher discriminatory ability of 24-h average aortic than brachial SBP to detect the presence of LVH (area under the curve: 0.73 versus 0.69; P = 0.007). A high degree of interindividual overlap regarding aortic 24-h average SBP level was found in individuals in whom the corresponding brachial measurements denoted different hypertension levels. CONCLUSION: These data suggest that aortic ABPM, when compared to brachial ABPM, improves the individualized assessment of the BP-associated heart damage.

Stress management and dietary counseling in hypertensive patients: a pilot study of additional effect.

BACKGROUND: In Western societies, cardiovascular (CV) disease is the primary cause of mortality, and high blood pressure (BP) is the main reversible factor leading to CV disease. Dietary habits and psychosocial stress contribute to the establishment of hypertension, while its role in the control of high BP is currently examined. In this study, we examined the effect and feasibility of a combined intervention of dietary education and stress management on the control of hypertension. METHODOLOGY: A randomized, controlled pilot study was designed to evaluate the effect of combined education on stress management techniques and dietary habits (Mediterranean diet principle) on office BP after eight weeks. RESULTS: Of the 45 randomized subjects, 36 were included in the final analysis (control group = 20 (age: 67 ± 12 years, 31.8%, males) and intervention group = 16 (age: 62 ± 12 years, 47%, males)). CV disease risk factors (except smoking), BP, dietary habits, perceived stress and physical activity (all assessed with validated questionnaires) were similar between the two groups at baseline. After eight weeks, office BP (systolic and diastolic) and perceived stress were significantly reduced, whereas the adherence in Mediterranean diet principle was significantly increased, but only in the intervention group. CONCLUSIONS: A combined intervention of stress management techniques and Mediterranean diet education seems to be beneficial for BP reduction. Such interventions could possibly serve as a complementary treatment along with drug therapy or in the early treatment of high normal BP. A call to action for designing epidemiological studies and evaluating the efficacy of such non-pharmacological treatment strategies is therefore warranted.

Long-term impact of multifactorial treatment on new-onset diabetes and related cardiovascular events in metabolic syndrome: a post hoc ATTEMPT analysis.

This post hoc analysis of the Assessing The Treatment Effect in Metabolic Syndrome Without Perceptible diabeTes (ATTEMPT) study assesses the 3½ year incidence of new-onset diabetes (NOD) and related cardiovascular disease (CVD) events in patients with metabolic syndrome (MetS), after multifactorial (lifestyle and drug, including atorvastatin) intervention. Patients were randomized to group A (low-density lipoprotein cholesterol [LDL-C] target < 100 mg/dL) and group B (< 130 mg/dL). The incidence of NOD during the 42-month follow-up was very low, 0.83 to 1.00/100 patient-years in patients with MetS and MetS with impaired fasting glucose, respectively. Older age, increased waist circumference, and persistent MetS were determinants of NOD. One CVD nonfatal event occurred in the 28 patients with NOD. Our findings suggest that treating the characteristics of MetS is achievable and beneficial. New-onset diabetes incidence and CVD events were negligible and not different from what is expected in the general population.

Assessing the treatment effect in metabolic syndrome without perceptible diabetes (ATTEMPT): a prospective-randomized study in middle aged men and women.

AIM: To assess the reduction in estimated cardiovascular disease (e-CVD) risk after multifactorial treatment for 6 months and follow this change during the next 3-years. PATIENTS-METHODS: This prospective, randomized, target driven study included 1,123 subjects (512/611 men/women, aged 45-65 years) with metabolic syndrome (MetS) without diabetes or CVD referred to specialist outpatient clinics. Patients were randomized to two treatment groups: group A with low density lipoprotein cholesterol (LDL-C) target of < 100 mg/dl and group B with a target of < 130 mg/dl. Atorvastatin was used in both groups on top of optimal multifactorial treatment, (quinapril, amlodipine, hydrochlorothiazide for hypertension, metformin for impaired fasting glucose, and orlistat for obesity). The e-CVD risk was calculated using the Framingham, the PROCAM and Reynold's equations. RESULTS: Reductions in e-CVD risk at 6 months were > 50%in all patients, but were superior in group A and in women. Reductions were even greater during the next 3-years and were mainly attributed to changes in lipid profile. Actual CVD events were 1 in group A and 13 in group B; p=0.0012. CONCLUSIONS: Attaining the treatment target of LDL-C < 100 mg/dl within multifactorial treatment of MetS by expert clinics, is achievable and beneficial even in patients without diabetes or known CVD. This induces a considerable e-CVD risk reduction in MetS patients. Actual CVD events were negligible, suggesting that e-CVD risk overestimates actual CVD risk in MetS, at least in patients achieving LDL-C < 100 mg/dl [ClinicalTrials.gov ID: NCT00416741].

Multiplexed analysis of angiogenesis and lymphangiogenesis factors predicts outcome for non-small cell lung cancer patients.

Angiogenesis and lymphangiogenesis are key components of non-small cell lung cancer (NSCLC) tumor growth and metastatic spread; however, the prognostic and predictive role of angiogenic and lymphangiogenic biomarkers remains controversial for NSCLC patients. We assessed VEGF, VEGFC, VEGFD, VEGFR3 protein expression, tumor microvessel, and lymphatic vessel (LmVD) density by immunohistochemistry in 103 NSCLC; biomarkers were analyzed individually as well as multiplexed with each other. No correlations were identified between VEGF, VEGFC, VEGFD, or LmVD and clinical characteristics. VEGFR3 was correlated with VEGFC (p = 0.03), VEGFD (p < 0.0001), and intratumor LmVD (p = 0.03). Tumors that did not express VEGFR3 had a worse prognosis (log rank p = 0.03). VEGF was significantly correlated with survival in adenocarcinomas (log rank p = 0.014) but not in squamous cell carcinomas (log rank p = 0.5). Multivariate Cox regression analysis confirmed the independent prognostic potential of VEGFR3 (hazard ratio (HR) = 0.05; 95% confidence intervals (CI) = 0.008-0.32, p = 0.002) for all patients and VEGF (HR = 8.69, 95% CI = 1.4-53.69, p = 0.02) for adenocarcinomas. When biomarkers were multiplexed, only stage and VEGFC expression were independent predictors of survival for all patients. Weighted expression of VEGFC, VEGFR3, and stage was used to build a prognostic classifier for stage I-IIIA patients; patients in the low risk group had prolonged survival compared with high risk patients (log rank p = 0.02). There was no association between biomarkers and early recurrence or response to treatment. Angiogenic and lymphangiogenic biomarkers studied define subgroups of patients at high risk and may be useful for prognostic stratification of NSCLC patients especially those with early stage disease.

Blood pressure levels constitute the most important determinant of the metabolic syndrome in a Mediterranean population: a discrimination analysis.

BACKGROUND: The aim of the study was to evaluate the relative importance of the determinants of the metabolic syndrome in a sample with metabolic syndrome from the Greek population. METHODS: A random sample of 824 male (56 ± 11 years) and 1,199 female (58 ± 10 years) subjects with metabolic syndrome [National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III)], but without diabetes mellitus or established cardiovascular disease, was selected from all over Greece. Principal components analysis (PCA) was applied to evaluate the interrelationships between the inherent characteristics of the metabolic syndrome. RESULTS: Among the participants, 87.6% had elevated blood pressure levels, 79.9% had hypertriglyceridaemia, 62.6% had low high-density lipoprotein cholesterol (HDL-C) levels, 71.4% had impaired fasting glucose (FG), and 91.5% had abdominal obesity. The most common combination was elevated blood pressure levels, abdominal obesity, impaired fasting glucose (FG), and hypertriglyceridemia (14.2%). PCA revealed three main components that explained 68.4% of the total variation. The first one was heavily loaded by blood pressure (28.6% of the total variation explained), followed by a component characterized by lipid variables (21.7%) and a component characterized by FG and waist circumference measurements (18.1% explained variation). CONCLUSIONS: The most dominant characteristic of metabolic syndrome participants from a Mediterranean country (Greece) was elevated blood pressure levels, which were present in all eight of the most common combinations of metabolic syndrome components, rendering the "hypertensive aspect" of metabolic syndrome the most common one. Because a significant proportion of hypertensive subjects with metabolic syndrome receive no treatment, or are poorly controlled, targeting blood pressure levels in the general population may assist in better preventing metabolic syndrome and its complications.

Nitric oxide, ammonia, and CRP levels in cirrhotic patients with hepatic encephalopathy: is there a connection?

GOALS: Comparison of nitric oxide (NO) levels in cirrhotic patients with and without hepatic encephalopathy (HE), evaluation of possible correlation between HE and other clinical or laboratory characteristics, and estimation of utilization of NO levels in clinical practice. BACKGROUND: HE is a neuropsychiatric complication of cirrhosis. The exact pathogenetic mechanisms underlying the presence of HE are not known. However, dysfunction of the NO pathway and ammonia detoxification are thought to play a major role. STUDY: Sixty-seven cirrhotic patients, 36 (53.7%) without HE, and 31 (46.3%) with HE were included in the study. Eighteen healthy individuals were used as control group. Clinical and laboratory data, including ammonia and stable end products of NO using Griess reaction, were collected. RESULTS: NOx levels were statistically significantly higher in cirrhotic patients (225.5 µmol/L) than in control group [(67.94 µmol/L) (P=0.000)]. NOx levels were, also, statistically significantly higher in patients with HE compared with patients without HE (324.67 µmol/L vs. 141.96 µmol/L, P=0.000). Significant correlation between the presence of HE and NOx, ammonia, C-reactive protein, albumin, Model for End-Stage Liver Disease score, and Child-Pugh classification revealed. NOx levels also correlated with severity of HE. NOx and ammonia are independent factors predicting HE according to regression analysis. Diagnostic accuracy for the diagnosis of HE using a combination of NOx and ammonia was superior compared with standalone NOx or ammonia utilization. CONCLUSIONS: NOx levels are correlated with the presence and severity of HE. NOx levels determination, in addition to ammonia levels, could contribute in diagnosis of HE.

Fever of unknown origin: discrimination between infectious and non-infectious causes.

OBJECTIVE: The present study aimed to develop and evaluate a simple diagnostic model that could aid physicians to discriminate between infectious and non-infectious causes of fever of unknown origin (FUO). DESIGN/SETTING/SUBJECTS: Patients with classical FUO were studied in two distinct, prospective, observational phases. In the derivation phase that lasted from 1992 to 2000, 33 variables regarding demographic characteristics, history, symptoms, signs, and laboratory profile were recorded and considered in a logistic regression analysis using the diagnosis of infection as a dependent variable. In the validation phase, the discriminatory capacity of a score based on the derived predictors of infection was calculated for FUO patients assessed from 2001 to 2007. RESULTS: Data from 112 individuals (mean age 56.5+/-11.2 years) were analyzed in the derivation cohort. The final diagnoses included infections, malignancies, non-infectious inflammatory diseases, and miscellaneous conditions in 30.4%, 10.7%, 33% and 5.4% of subjects, whereas 20.5% of cases remained undiagnosed. C-reactive protein>60 mg/L (odds ratio 6.0 [95% confidence intervals 2.5, 9.8]), eosinophils<40/mm(3) (4.1 [2.0, 7.3]) and ferritin<500 microg/L (2.5 [1.3, 5.2]) were independently associated with diagnosis of infection. Among the 100 patients of the validation cohort, the presence of > or =2 of the above factors predicted infection with sensitivity, specificity, and positive and negative predictive values of 91.4%, 92.3%, 86.5%, and 95.2%, respectively. CONCLUSIONS: The combination of C-reactive protein, ferritin and eosinophil count may be useful in discriminating infectious from non-infectious causes in patients hospitalised for classical FUO.

Polymorphisms of fractalkine receptor CX3CR1 gene in patients with symptomatic and asymptomatic carotid artery stenosis.

AIM: The chemokine fractalikine is expressed in vascular endothelium, exerting a pro-atherogenic effect. Two single-nucleotide polymorphisms of the CX3CR1 gene (T280M and V249I) affect frac-talkine receptor expression and function. We aimed to assess the prevalence of CX3CR1 polymor-phisms and the association with ischemic cerebrovascular attacks in a cohort of carotid atheromatous disease patients and age-matched controls. METHODS: Using PCR-RFLP, we analyzed allelotypes for T280M and V249I in 150 patients with and 151 controls without carotid atherosclerosis assessed using carotid duplex ultrasound; the subjects were patients admitted for any reason to a tertiary hospital. Genotype data were compared with modifiable risk factors for cerebrovascular disease and the reason for admission, using ischemic stroke as an endpoint. Stroke types associated with carotid atherosclerosis were analysed separately. RESULTS: The M280 allelic frequency was lower among carotid atherosclerosis patients than controls (0.15 versus 0.23, adjusted OR 0.47, 95% CI 0.30-0.74). Absence of M280 allele was an indepen-dent factor associated with carotid atherosclerosis (OR 3.70, 95% CI 1.92-7.14), stronger than hypertension, dyslipidemia, diabetes and cigarette smoking. The I249 allele was also under-repre-sented in carotid atherosclerosis; this was not statistically significant. T280M and V249I genotypes were not associated with admission due to ischemic stroke of the large vessel subtype (TOAST classi-fication, 73 episodes), whereas carotid atherosclerosis, previous ischemic event, age, hypertension, diabetes, hyperlipidemia and cigarette smoking were all independently associated. CONCLUSIONS: The M280 fractalkine receptor gene allele is associated with a lower risk of carotid ath-eromatous disease, independent from the modifiable cerebrovascular risk factors.