Arterial stiffness indexes and serum cytokine levels in seronegative spondyloarthritis: relationships between stiffness markers and metabolic and immunoinflammatory variables.

OBJECTIVE: The aim of this study was to investigate the relationship between immunoinflammatory markers and indexes of arterial stiffness in patients with seronegative spondyloarthritis (SpA). METHOD: We enrolled consecutive patients with inflammatory seronegative SpA referred to a rheumatology outpatient clinic. Control subjects were patients admitted in the same period for any cause other than chronic inflammatory disease or acute cardiovascular and cerebrovascular events. Carotid-femoral pulse wave velocity (PWV) was measured and the aortic pressure waveform was used to calculate the augmentation index (Aix). We also evaluated plasma levels of C-reactive protein (CRP), interleukin (IL)-1ß, tumour necrosis factor (TNF)-α, and interleukin (IL)-6 as markers of immunoinflammatory activation. RESULTS: This study enrolled 53 patients with SpA and 55 control subjects. After adjustment for blood glucose, cholesterol, and triglyceride levels, and systolic (SBP) and diastolic blood pressure (DBP), patients with seronegative SpA showed higher mean PWV and Aix compared to controls. Moreover, in patients with seronegative SpA, we observed higher mean plasma levels of IL-6, IL-1ß, and TNF-α in subjects with mean PWV > 8 m/s in comparison with those with PWV < 8 m/s. Multivariate analysis revealed a significant association between PWV > 8 m/s and male gender, age, diabetes, hypertension, low density lipoprotein cholesterol (LDL-C) > 120 mg/dL, total cholesterol (TC) > 200 mg/dL, coronary artery disease (CAD), microalbuminuria, carotid plaque, and plasma levels of IL-6, IL-1ß, and TNF-α. CONCLUSIONS: These findings emphasize the role of inflammatory variables and metabolic factors in indexes of high arterial stiffness. Thus, an inflammatory-metabolic background may influence the pathogenesis of increased arterial stiffness in seronegative inflammatory arthritis.

Use of QT intervals for a more accurate diagnose of syncope and evaluation of syncope severity.

BACKGROUND: This study aimed to evaluate the use of QT intervals, their diagnostic predictive value in patients with syncope and their relationship with syncope severity. METHODS: One hundred and forty nine patients with a diagnosis of syncope were admitted to Internal Medicine departments at the University of Palermo, Italy, between 2006 and 2012, and 140 control subjects hospitalised for other causes were enrolled. QT maximum, QT minimum, QTpeak, QT corrected, QT dispersion and Tpeak-to-Tend interval were compared between two groups. The paper medical records were used for scoring with San Francisco Syncope Rule (SFSR), Evaluation of Guidelines in SYncope Study (EGSYS) score and Osservatorio Epidemiologico sulla Sincope nel Lazio (OESIL) risk score. RESULTS: Mean QTc (p < 0.0005), mean QTmax (p < 0.0005), mean QTdisp (p < 0.0005), mean QTpeak (p = 0.005) and mean TpTe (p = 0.018) were significantly longer in patients with syncope compared with control subjects. A QTc > 424.8 ms (sensibility: 81.88 - specificity: 57.86) showed the greatest predictive value for diagnosis of syncope. On the EGSYS score and on the OESIL score, QTc was significantly prolonged in high-risk patients compared with low-risk patients. On the San Francisco Syncope Rule, QTc and QTdisp were significantly prolonged in high-risk patients compared with low-risk patients. CONCLUSION: Mean QTc, mean QTdisp, mean TpTe, mean QTmax and mean QTpeak were significantly longer in patients with syncope compared with control subjects. Furthermore, prolonged QTc and QTdisp were associated with major severe syncope according to San Francisco Syncope Rule, EGSYS and OESIL risk scores.

Metabolic and anti-inflammatory effects of a home-based programme of aerobic physical exercise.

AIMS: Regular exercise demonstrated the ability to provide enormous benefits to many diseases, atherosclerotic-based, degenerative and neoplastic, but also to grant anti-inflammatory actions, assessed by various authors in different populations. Despite of these clear benefits, many patients are unable to attain long-term results through chronic physical activity for different causes. On this basis, the aim of our study was to assess the metabolic and anti-inflammatory effects of a home-based programme of fast walking in patients affected by metabolic syndrome (MS). MATERIALS AND METHODS: We enrolled 176 subjects with MS as stated by ATP III criteria. Patients were invited to walk for 1 h every day 5 days a week for 24 weeks. The walking velocity was required higher than the one retained 'comfortable' by the patient, previously assessed in the run-in visit. Monitoring of physical activity was carried out through an OMRON step counter type Walking Style II. All the subjects enrolled completed the training period. RESULTS: After the 24 weeks of intervention body mass index changed from 31.59 to 29.23 (p < 0.001); mean waist circumference passed from 105.19 to 100.06 cm (p < 0.001); mean fasting glucose changed from 119.76 to 114.32 mg/dl (p < 0.001); for diabetic population (n = 70) mean glicated haemoglobin levels changed from 7.38% to 6.86% (p < 0.001); total cholesterol levels from 192.15 to 185.78 mg/dl (p < 0.001); HDL cholesterol levels raised from 44.03 to 47.63 mg/dl (p < 0.001); triglycerides levels lowered from 148.29 to 135.20 mg/dl (p < 0.001); WBC changed from 7361.08 to 7022.56/mm(3) (p < 0.001); hs-CRP from 0.55 to 0.28 mg/dl (p < 0.001); fibrinogen serum levels lowered from 339.68 to 314.86 mg/dl (p < 0.001). CONCLUSIONS: A long-term home-based programme of aerobic physical activity improves metabolic asset and reduces systemic inflammation in sedentary people.

Effects of clinical and laboratory variables at admission and of in-hospital treatment with cardiovascular drugs on short term prognosis of ischemic stroke. The GIFA study.

INTRODUCTION: No information exists, to our knowledge, about the possible role of cardiovascular drug administration in the acute phase of ischemic stroke and possible effects on stroke outcome. The aim of our study was to evaluate the relationship between in-hospital treatment with cardiovascular drugs in patients with acute ischemic stroke and some outcome indicators. METHODS AND RESULTS: 1096 subjects enrolled in the GIFA study, who had a main discharge diagnosis of ischemic stroke represent the final sample. Drugs considered for the analysis were the following: ACE-inhibitors (ACEI), angiotensin II receptor blockers (ARBs), statins, calcium-channel-blockers (CCBs), antiplatelet (APL) drugs, antivitamin-k (VKAs), and heparins. As outcome indicators we choose in-hospital mortality, cognitive function evaluated by Hodkinson Abbreviated Mental Test (HAMT), and functional status evaluated by activity daily living (ADL). Indicators of a good outcome were: no in-hospital mortality, HAMT >6 and 0 ADL impaired. Patients with a good outcome showed a higher rate of in-hospital treatment with ACE-inhibitors, calcium-channel blockers and a lower rate of pre-treatment with heparin. CONCLUSIONS: Our study suggests that if a patient with acute ischemic stroke has higher SBP at admission, higher total cholesterol plasma levels, a lower Charlson index and is treated with ACE-inhibitors, calcium channel blockers and antiplatelet drugs, the short term outcome is better in terms of in-hospital mortality and functional indicators such as cognitive and functional performance at discharge.

Aerobic physical activity based on fast walking does not alter blood pressure values in non-dipper essential hypertensives.

AIM: Walking is a very acceptable form of aerobic exercise. Several trials have demonstrated significant benefits of fast walking on the risk factors of cardiovascular disease, particularly for hypertension. Aim of our study was to assess whether physical activity obtained through fast walking might lead to a different reduction of blood pressure levels in hypertensive patients in relation to different circadian profile of blood pressure. METHODS: We have enrolled 84 hypertensive patients, with evidence of stage I hypertension and non-dipper nocturnal profile. All subjects underwent a six weeks physical intervention based on fast walking, three sessions a week. Main outcome measurements were diurnal, nocturnal and 24-h blood pressure levels. RESULTS: After the sixth week of physical exercise there was not any significant change in 24-hour mean systolic blood pressure and diastolic blood pressure ABPM values when compared to baseline (respectively 143.2±5.2 vs. 141±4.4 and 91.4±4.8 vs. 90.1±2.5); also no differences in heart rate have been found. CONCLUSION: In non-dipper hypertensives a light aerobic program of physical activity based on fast walking seems to be less effective to reduce blood pressure values, contrary to what has been observed in dipper ones.

Effects of physical exercise on inflammatory markers of atherosclerosis.

It is well established that physically fit individuals have a reduced risk of developing CVD (cardiovascular disease) and other age-related chronic disorders. Regular exercise is an established therapeutic intervention with an enormous range of benefits. Chronic low-grade systemic inflammation may be involved in atherosclerosis, diabetes and in pathogenesis of several chronic pathological conditions; recent findings confirm that physical activity induces an increase in the systemic levels of a number of cytokines and chemokines with anti-inflammatory properties. The possibility that regular physical exercise exerts anti-inflammation activity, being the interaction between contracting muscle and the other tissues and the circulating cells mediated through signals transmitted by "myokines" produced with muscle contractions. To date the list of myokines includes IL-6, IL-8, and IL-15. During muscle contractions are also released IL-1 receptor antagonis and sTNF-R, molecules that contribute to provide anti-inflammatory actions. Nevertheless discrepancies, analysis of available researches seem to confirm the efficacy of regular physical training as a nonpharmacological therapy having target chronic low-grade inflammation. Given this, physical exercise could be considerate a useful weapon against local vascular and systemic inflammation in atherosclerosis. Several mechanisms explain the positive effect of chronic exercise, nevertheless, these mechanisms do not fully enlighten all pathways by which exercise can decrease inflammation and endothelial dysfunction, and hence modulate the progression of the underlying disease progress.

Effects of ACE-inhibitors and angiotensin receptor blockers on inflammation.

The role of inflammation in cardiovascular disease and in hypertensive disease above all, is complex. Several studies confirm that activation of renin-angiotensin-aldosterone system (RAAS), through increase in the production of angiotensin II (Ang II), is closely related to local vascular inflammation. Over the BP lowering effects of anti-hypertensive treatments, several ancillary effects for every class may be found, distinguishing the various drugs from one another. Given the pro-inflammatory effects of Ang II and aldosterone, agents that interfere with the components of RAAS, such as ACE inhibitors, Angiotensin Receptor Blockers (ARBs), and mineralocorticoid receptor antagonists (spironolactone or the more selective eplerenone), represent logical therapeutic tools to reduce vascular inflammation and cardiovascular risk, as suggested in large clinical trials in patients with hypertension and diabetes. Regarding ACE inhibitors, actually there is no convincing evidence indicating that ACEi's reduce plasma levels of major inflammatory markers in hypertension models. Lack of evidence concerns especially these inflammation markers, such as fibrinogen of CRP, which are less closely related to atherosclerotic disease and vascular damage and conversely are affected by several more aspecific factors. Results obtained by trials accomplished using ARBs seem to be more univocal to confirm, although to great extent, these is an anti-inflammatory effect of drugs blocking AT1 receptor. In order to strictly study the effects of blockage of RAAS on inflammation, future studies may explore different strategies by, for example, simultaneously acting on the ACE and the AT1 angiotensin receptors.

Changes in natriuretic peptide and cytokine plasma levels in patients with heart failure, after treatment with high dose of furosemide plus hypertonic saline solution (HSS) and after a saline loading.

BACKGROUND AND AIMS: Neurohormonal activation and inflammation characterizes heart failure, relates to outcome, and is a therapeutic target. The aim of this study was to evaluate the effects of high-dose furosemide plus small-volume hypertonic saline solutions (HSS) on natriuretic peptides and immuno-inflammatory marker levels and to analyze, after treatment, the response to acute saline loading. METHODS AND RESULTS: 120 patients with heart failure treated with high-dose furosemide+HSS (Furosemide/HSS group) were matched with: 30 subjects with heart failure treated with high-dose furosemide (furosemide group), 30 controls with asymptomatic left-ventricular dysfunction (ALVD) (asymptomatic group) and 30 controls without heart failure or ALVD (Healthy group). We evaluated plasma levels of natriuretic peptides and cytokine levels in baseline, after treatment and after acute saline load. After treatment with high-dose furosemide+HSS compared to treatment with furosemide alone we observed a significant lowering of ANP [96 (46.5-159.5) pg/ml vs 64 (21-150) pg/ml], BNP [215.5 (80.5-487) pg/ml vs 87 (66-141.5) pg/ml], TNF-α [389.5 (265-615.5) pg/ml vs 231.5 (156-373.5) pg/ml], IL-1ß [8 (7-9) pg/ml vs 4 (3-7) pg/ml], IL-6 [5 (3-7.5) pg/ml vs 3 (2-4) pg/ml], plasma values and after an acute saline load, a lower percentage change of ANP (+18.6% vs +28.03% vs +25% vs +29%), BNP (+14.5% vs +29.2% vs +30% vs +29.6%) TNF-α (+10.8% vs +15.8% vs +17.8% vs +11.3%), IL-1ß (+20% vs 34.4% vs 40% vs 34.4%) compared to control groups. CONCLUSIONS: Treatment with HSS could be responsible for a stretching relief that could influence natriuretic and immuno-inflammatory markers.

Fetuin-A and CD40 L plasma levels in acute ischemic stroke: differences in relation to TOAST subtype and correlation with clinical and laboratory variables.

INTRODUCTION: Accumulating evidence suggests that inflammation plays an important role in the acute phase of ischemic stroke. CD40 L is a well recognized atherosclerotic inflammatory marker, whereas recent evidence suggests a pro-inflammatory role of Fetuin-A. To analyze the role of an inflammatory marker such as CD40 L and of a candidate pro-inflammatory marker such as Fetuin-A in acute stroke we evaluated their serum levels in subjects with acute ischemic stroke and their possible association with other laboratory and clinical variables. MATERIALS AND METHODS: We enrolled 107 consecutive patients with a diagnosis of acute ischemic stroke admitted to the Internal Medicine Department at the University of Palermo between November 2006 and January 2008, and 102 hospitalized control patients without a diagnosis of acute ischemic stroke. RESULTS: Patients with acute ischemic stroke in comparison to control subjects without acute ischemic stroke had significantly higher CD40 L levels and Fetuin-A serum levels. No significant differences in plasma CD40 L or Fetuin-A levels among different TOAST groups were detected. At intragroup (intra-TOAST-subtype) correlation analysis, among subjects classified as lacunar, CD40 L plasma levels were positively correlated with LDL-cholesterol and with diabetes, whereas Fetuin-A was significantly (positively) correlated with hypertension and white blood cell count. Among subjects with LAAS subtype, CD40 L levels were positively correlated with triglyceride plasma levels and Fetuin-A, whereas Fetuin-A levels were positively correlated with LDL-cholesterol. DISCUSSION: Our findings suggest a pro-inflammatory role of Fetuin-A and CD40 L in acute stroke setting. Whether this role should be construed as direct or as a simple expression of a general inflammatory activation will be up to future studies to clarify.

Clinical Trial: High-dose furosemide plus small-volume hypertonic saline solutions vs. repeated paracentesis as treatment of refractory ascites.

BACKGROUND: In patients with cirrhosis, ascites is defined as refractory when it cannot be mobilized or recurs early in standard diuretic therapy. AIM: To compare the safety and efficacy of intravenous high-dose furosemide + hypertonic saline solutions (HSS) with repeated paracentesis in patients with cirrhosis and refractory ascites. PATIENTS AND METHODS: Eighty-four subjects (59/25 M/F) with cirrhosis, mostly of viral aetiology, admitted for refractory ascites, were randomly assigned to receive furosemide (250-1000 mg/bid i.v.) plus HSS (150 mL H(2)O with NaCl 1.4-4.6% or 239-187 mEq/L) (60 patients, Group A) or to repeated paracentesis and a standard diuretic schedule (24 patients, Group B). RESULTS: During hospitalization, Group A patients had more diuresis (1605 +/- 131 mL vs. 532 +/- 124 mL than Group B patients; P < 0.001) and a greater loss of weight at discharge (-8.8 +/- 4.8 kg vs. -4.5 +/- 3.8 kg, P < 0.00). Control of ascites, pleural effusions and/or leg oedema was deemed significantly better in Group A. CONCLUSIONS: This randomized pilot study suggests that HHS plus high-dose furosemide is a safe and effective alternative to repeated paracentesis when treating hospitalized patients with cirrhosis and refractory ascites. Larger studies will be needed to evaluate long-term outcomes such as readmission and mortality.

Recurrent venous thromboembolism complicated by heparin-induced thrombocytopenia as a first manifestation of an occult cancer: a case report.

Heparin-Induced Thrombocytopenia (HIT) is a serious and potentially fatal complication of patients on heparins. Its management is difficult and it can be more complicated in patients with cancer because of the hemorrhagic risk carried out by direct inhibitor of thrombin, the currently approved drug for HIT. At present, it is not clear whether cancer patients also have an increased risk of HIT. We describe the case of a patient with occult cancer at the moment of the index venous thrombosis, who developed Deep Vein Thrombosis (DVT) and concomitant HIT with thrombotic complications (recurrent contra-lateral venous thrombosis). The management of HIT was efficaciously based on the combined use of alternative antithrombotic regimens (Dermatan-Sulphate and Defibrotide), without an increased risk of bleeding. This case highlights the potential relationship between DVT, as first episode of an occult cancer, and the risk of developing HIT. The use of alternative antithrombotic therapy seems to be efficacious even in this high-risk cancer patient.

Ischemic stroke in patients with diabetic foot.

AIM: The diabetic foot syndrome is the most frequent cause of hospitalization of diabetic patients and one of the economically most demanding complications of diabetes. People with diabetes have been shown to have higher mortality than people without diabetes, but the cerebrovascular risk profile of these patients is not fully evaluated. The aim of our study was to evaluate the possible role of diabetic foot as a cerebrovascular risk marker in type 2 diabetic patients. METHODS: We enrolled 102 type 2 diabetes patients with diabetic foot and 123 diabetic patients without diabetic foot. RESULTS: Statistically significant differences were found in the distribution of the main cardiovascular risk factors with exception of hypertension. We observed a higher prevalence of previous cerebrovascular events (transient ischemic attack, ischemic stroke) and of incidence of new onset cerebrovascular events at a 5-year follow-up. Regarding clinical subtype of ischemic stroke classified according to Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification on a retrospective and prospective basis, we observed a higher prevalence of both the lacunar and large artery atherosclerosis subtype with a slight higher prevalence of lacunar subtype in patients with diabetic foot. CONCLUSION: Our results show a worse cerebrovascular risk profile in diabetic patients with diabetic foot than in diabetic subjects without foot ulceration with a higher prevalence of cardiovascular risk factors and of anamnestic cerebrovascular events and incidence of new cerebrovascular events at a 5-year follow-up.

A case control study between diabetic and non-diabetic subjects with ischemic stroke.

AIM: The clinical and prognostic profile of diabetic stroke patients is still an unclarified topic. The aim of the present study is to compare clinical features and risk factor profile in diabetics and in non-diabetics affected by acute ischemic stroke. METHODS: We have included 98 diabetics and 102 matched non-diabetic subjects affected by acute ischemic stroke and matched by age (+/-3 years) and gender. We determined the Scandinavian Stroke Scale (SSS) on admission and the Rankin disability scale on discharge and after a 6 months follow-up. Ischemic stroke has been classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. We anamnestically evaluated the presence of hypertension, hypercholesterolemia, any records of transient ischemic attack, and stroke. Using conditional logistic regression analysis, we calculated adjusted odds ratio (OR) and 95% confidence interval (CI). RESULTS: Diabetes was associated with lacunar ischemic stroke subtype (OR 3.89, 95% CI 2.23-6.8), with a record of hypertension (OR 2.53, 95% CI 1.48-4.32), and with a better SSS score at admission (OR 0.58, 95% CI 0.36-0.96). The association of diabetes with lacunar stroke remained significant also after adjustment for hypertension (adjusted OR 3.37, 95% CI 1.9-5.99) or for large artery atherosclerotic and cardioembolic stroke subtypes (adjusted OR 2.69, 95% CI 1.08-6.69). CONCLUSIONS: Our study shows some significant differences in acute ischemic stroke among diabetics in comparison with non-diabetics (higher frequency of hypertension, higher prevalence of lacunar stroke subtype, lower neurological deficit at admission in diabetics).

Successful salvage therapy of intravenous cyclophosphamide for refractory polymyositis in an elderly patient: case report.

Dermatomyositis and polymyositis may affect children and adults and are now widely recognized as major causes of disability which, thanks to the introduction of immunosuppressive drugs, is often treatable, at least to some extent. Few data exist regarding polymyositis in elderly patients. We describe a case of refractory life-threatening polymyositis in an elderly patient, successfully treated with intravenous cyclophosphamide.

Immunoinflammatory activation during the acute phase of lacunar and non-lacunar ischemic stroke: association with time of onset and diabetic state.

Several studies have stressed the involvement of inflammation in the pathophysiology of acute brain ischemia, but the role of immunoinflammatory activation in diabetic stroke patients has not yet been fully evaluated. The aim of our study was to evaluate immunoinflammatory activation of acute phase of stroke in relation to time of symptoms onset, diabetic state and diagnostic subtype. We enrolled 60 patients (32 diabetics; 28 non- diabetics) with acute ischemic stroke and 123 subjects without acute ischemic stroke, and measured levels of IL-1beta, TNF-alpha IL-6, IL-10, E-selectin, P-selectin, sICAM-1, sVCAM-1, VWF, 24-72 h and 7-10 days after stroke onset; TPA, PAI-1 plasma levels at 24-72h. Our stroke patients exhibited significantly higher plasma levels of cytokines, selectins, adhesion molecules and PAI-1, and diabetic stroke patients exhibited higher plasma levels of PAI-1 in comparison with non-diabetic ones. Lacunar strokes in comparison with those non-lacunar exhibited significantly lower levels of TNF-alpha and IL1-beta P-selectin and ICAM-1. Moreover, diabetic patients with lacunar strokes exhibited a minor grade of immunoinflammatory activation of the acute phase at 24-72h and 7-10 days after stroke onset. The minor grade of immunoinflammatory activation of patients with lacunar strokes, particularly diabetic ones, could be related to the minor extension of the infarct size, owing to the typical microvascular disease of diabetic subjects which could also explain the reported better outcome of this subtype of ischemic stroke.

Risk factors profile and clinical outcome of ischemic stroke patients admitted in a Department of Internal Medicine and classified by TOAST classification.

AIM: A classification of ischemic stroke subtypes tailored for individual patients is hard to achieve. In 1993, the Trial of Org 10172 in Acute Stroke Treatment (TOAST) group developed a new system to classify the subtypes of ischemic stroke. In our study we applied the TOAST classification to a group of consecutive patients affected by ischemic stroke, to evaluate outcome and factors associated to each stroke subtype. METHODS: To evaluate the prognosis and the associated factors of ischemic stroke subtypes, we classified according to the TOAST classification a cohort of 159 consecutive patients affected by an acute ischemic stroke. We evaluated neurological deficit at admission by Scandinavian Stroke Scale and scored disability at discharge and 6 months after discharge using the Rankin disability scale. We determined 30 days survival and anamnestically evaluated major vascular risk factors. RESULTS: Patients with cardioembolic stroke and stroke of undetermined etiology had a greater neurological deficit on admission and the worst prognosis either in terms of disability or mortality. Lacunar stroke had the least neurological deficit at admission and the best prognosis. Hypercholesterolemia and smoking were more frequent among patients with large artery atherosclerotic stroke. Hypertension, a history of transient ischemic attack and diabetes were more frequent among patients with lacunar stroke. A weak association with hypertension and smoking was observed for cardioembolic stroke. CONCLUSIONS: The TOAST classification is useful in the clinical setting because it identifies ischemic stroke subtypes with different prognosis and with a different profile of associated factors.