Three-dimensional echocardiographic evaluation of the right ventricle in patients with uncomplicated systemic lupus erythematosus.

Our aim was to identify subclinical right ventricular (RV) alterations in systemic lupus erythematosus (SLE) by combining standard and three-dimensional echocardiography (3DE). Fifty SLE patients without concomitant cardiac disease and 50 healthy controls, matched for age and gender, were enrolled. Disease damage was evaluated by inflammatory markers and SLE damage index. All patients underwent an echo-Doppler examination with 3DE assessment of RV function, RV septal and lateral longitudinal strain. The two groups had comparable body mass index and blood pressure. RV transversal middle diameter and pulmonary arterial pressure were significantly higher in SLE compared to controls. By 3DE, RV end-systolic volume ( p = 0.037) was greater, whereas stroke volume ( p = 0.023), ejection fraction ( p < 0.0001) and septal and lateral longitudinal strain (both p < 0.0001) were lower in SLE. SLE damage index ≥ 1 was negatively associated with tricuspid annular plane systolic excursion (TAPSE) ( p < 0.002), tricuspid E/A ratio ( p = 0.003), RV ejection fraction ( p < 0.05), lateral longitudinal strain ( p < 0.0001) and septal longitudinal strain ( p = 0.04). By separate multivariate models, after adjusting for age, C reactive protein and proBNP, SLE damage index was independently associated with TAPSE ( p = 0.009) and RV lateral longitudinal strain ( p = 0.007). In conclusion, a subclinical RV systolic dysfunction is detectable in SLE by 3DE, RV lateral wall strain being a key parameter. RV dysfunction is associated with cumulative disease damage.

Stapled haemorrhoidopexy vs. Milligan-Morgan haemorrhoidectomy for grade III haemorrhoids: a randomized clinical trial.

The aim of this double blind randomized clinical trial was to compare the short-term and long-term outcomes of stapled haemorrhoidopexy (SH group) performed using a circular stapler with that of the Milligan-Morgan haemorrhoidectomy (MMH group). A total of 79 consecutive patients with grade III haemorrhoids were randomized into two groups treated with SH (n. 39) and MMH (n. 40). The outcomes of the procedures were evaluated postoperatively and over a follow-up period of minimum 2 years. Patients undergoing the SH procedure showed greater short term advantages than MMH group with reduced pain, shorter length of hospital stay, earlier return to work and high patient satisfaction. Long-term follow-up has indicated more favourable results in MMH group in terms of resumption of symptoms with absence of residual prolapse and risk of recurrence of prolapse. At two years follow-up recurrent prolapse was confirmed in six patients of SH group (13%) whereas in none of the MMH group. At six months follow-up there weren't significant difference in the mean satisfaction score for the two groups. At two years the mean satisfaction score was higher in the MMH group vs SH group. Seven patients in the SH group needed a reoperation whereas none in MMH group. From January 2009, in our Surgery Unit the patients are always informed about a higher recurrence rate of SH and we perform this technique only when the patient choices to accept this risk to take advantage of the short-term benefits of this procedure.

Traumatic abdominal wall hernia. Case report.

Despite the high incidence of abdominal traumas, traumatic abdominal wall hernias (TAWHs) remain rare probably because of elasticity of the abdominal wall. The TAWH is due to blunt abdominal trauma with disruption of the abdominal wall muscles and fascia with intact overlying skin. TAWH can be classified into high energy injures (generally motor vehicle accidents) and low energy injures (impact on a small blunt object). Common example of the latter type is a fall onto a bicycle handlebar. The mechanism of the trauma includes sudden increase of intra-abdominal pressure and extensive shear forces applied to the abdominal wall. The diagnosis of TAWH is difficult in the Emergency Room because during the primary diagnostic process most attention is directed toward the detection of internal injures and TAWH can be missed. In this article we report a case of TAWH caused by a work accident (an heavy steel tube fallen onto the abdominal wall of the patient from a height of five meters) with delayed diagnosis.

Inferior epigastric artery pseudoaneurysm secondary to port placement during a robot-assisted laparoscopic radical cystectomy.

Pseudoaneurysm occurs when the artery wall is damaged and the blood is contained by the surrounding tissues with the eventual formation of a fibrous sac communicating with the artery. We report a case of a 74-year-old man with inferior epigastric artery (IEA) pseudoaneurysm secondary to an 8-mm port placement during a robot-assisted laparoscopic radical cystectomy with ureteroileocutaneostomy. The pseudoaneurysm was initially diagnosed by contrast-enhanced ultrasound (CEUS); subsequently, a computed tomography (CT) scan and an angiography test were performed. The pseudoaneurysm was then treated successfully with embolization of the inferior epigastric artery. Awareness of this rare complication is of clinical importance to avoid excessive morbidity of affected individuals.

Longer-acting factor VIII to overcome limitations in haemophilia management: the PEGylated liposomes formulation issue.

Injected factor VIII (FVIII), the current treatment for haemophilia A, leads to major improvements in the quality of life and life expectancy of individuals with this disorder. However, because injected FVIII has a short half-life in vivo, this strategy has major limitations for highly demanding regimens (e.g. prophylaxis, immune tolerance induction, surgery). Newer formulations of longer-acting FVIII are presently under investigation. The use of low molecular weight polyethylene glycol (PEG)-containing liposomes as carriers for recombinant FVIII (rFVIII) results in the prolongation of haemostatic efficacy. Data from preclinical experiments in mice, early clinical evaluations, and pharmacokinetics and pharmacodynamics results indicate that an rFVIII pegylated liposomal formulation may provide potential clinical benefit to patients with severe haemophilia A by prolonging the protection from bleeding. In light of this potential clinical benefit, a multicentre, randomized, active-controlled, non-inferiority phase II trial with two parallel treatment arms and equal randomization after stratification for the presence or absence of target joints in patients and for ages >/=18 years vs. <18 years is currently being conducted. The study will test the hypothesis that rFVIII-Lip once-weekly prophylaxis is not inferior to rFVIII-water for injection thrice-weekly prophylaxis. A total of 250 patients will be enrolled with severe haemophilia A (<1% FVIII) on on-demand or secondary prophylaxis treatment and with documented bleeds or injections during the 6 months before study entry. Sixty-four centres in 14 different countries are involved in the study; recruitment is underway. In Italy, six centres have already included 15 patients (no screening failure). Eight of these patients have completed the run-in phase and have begun the home treatment. No unexpected serious adverse events have been reported thus far. Data emerging from this phase II study will help collect relevant data to overcome current limitations in haemophilia management by employing treatment with longer-acting rFVIII.

Cardiovascular events in patients with antiphospholipid antibodies: strategies of prevention.

Antiphospholipid antibodies are a heterogeneous group of auto-antibodies against phospholipids-binding proteins. The antiphospholipid syndrome is an autoimmune disorder characterized by the clinical association of antiphospholipid antibodies with a condition of hypercoagulability that can affect any blood vessel. Involvement of larger vessels, such as arteries or veins, manifests in the form of thrombosis or thromboembolism, whereas involvement of small vessels manifests as thrombotic micro-angiopathy. The antiphospholipid syndrome is also characterized by the presence of recurrent fetal loss. Patients who are persistently positive for antiphospholipid tests, and who have an arterial thrombosis or venous thrombosis history, are at increased risk of recurrence. Oral anticoagulant therapy is the mainstay of treatment for the thrombotic manifestations of the syndrome. Therapy with anticoagulant drugs should be long-term. On the other hand, although the thromboembolic potential of antiphospholipid antibodies has been well documented, there is still no general consensus on the prophylactic treatment of antiphospholipid antibodies carriers who have never developed vascular/obstetric manifestations. The effect of primary prophylaxis in antiphospholipid antibodies positive individuals is not well known and no evidence-based recommendations exist for thrombosis prevention in these individuals. However, the presence of risk factors for thrombosis increases the risk of first event of antiphospholipid antibodies positive patients. In conclusion, there is still much to learn on primary prophylaxis of asymptomatic antiphospholipid antibodies carriers. Hopefully, evidence-based guidelines will be available in the future.

[Thyroid function and obesity]. / La funzione tiroidea in corso di obesità.

A relationship between thyroid function and obesity seems likely, mainly influenced by the insulin resistance. Whether variations in TSH and/or thyroid hormones, within a normal range, can influence body weight or if obesity per se can alter thyroid function has not been clarified so far. Further studies are necessary to assess the link between thyroid function and body weight, that must consider not only changes of thyroid hormones, but also body fat distribution, obesity duration and the state of low grade inflammation. It is recognized that thyroid function is linked not only to body mass index, but also to body composition and, particularly, to the amount and percentage of fat mass.

A rare case of renal tumor in children: clear cell sarcoma.

Clear cell sarcoma of the kidney is an uncommon renal neopla sm of childhood. It represents about 4% of childhood malignant neoplasms and is generally more common in children under 5 years of age. In the present article, we describe the case of a 12-year-old male patient who came to our observation with left renal mass and with a clinical-laboratory picture indicative of inflammatory pathology.

Percutaneous radiofrequency thermal ablation for hepatocellular carcinoma.

BACKGROUND: Radiofrequency thermal ablation is the first therapeutic option in percutaneous treatment of hepatocellular carcinoma but data on its long-term efficacy and safety are not conclusive. AIM: This study reports a prospective survey on radiofrequency thermal ablation in north-east Italy. METHODS: Data were collected on 401 patients with hepatocellular carcinoma (males 301, mean age: 68 years) treated by radiofrequency thermal ablation in 13 centres. Indication to treatment was: single nodule not eligible for surgery in 77% of patients, 2-3 nodes in 18% and multiple lesions in 5%. Mean size was 3 cm (1-8 cm). Treatment response was assessed at 1 month by spiral computerized tomography and then with ultrasound examination and new spiral computerized tomography. RESULTS: Complete response was obtained in 67% of patients and in 27% response was 75-99%. Complete response raised to 77% in lesions smaller than 3 cm. The morbidity rate was 34%; the mortality was 0.5%, seeding was observed in four patients. Ten patients presented an unexpected rapid disease progression. CONCLUSION: The above data show that by radiofrequency thermal ablation, complete response can be achieved only in about two-third of the cases, clearly less than expected, and that, beyond seeding, unexpected progression can be observed.

Oxidative stress and platelet activation in homozygous homocystinuria.

BACKGROUND: Severe hyperhomocysteinemia due to cystathionine beta-synthase deficiency (CbetaSD) is associated with early atherothrombotic vascular disease. Homocysteine may exert its effects by promoting oxidative damage. In the present study, we investigated whether in vivo formation of 8-iso-prostaglandin (PG) F(2alpha), a platelet-active product of arachidonic acid peroxidation, is enhanced in CbetaSD and whether it correlates with in vivo platelet activation, as reflected by thromboxane (TX) metabolite excretion. METHODS AND RESULTS: Urine and blood samples were obtained from patients with homozygous CbetaSD (n=13) and age-matched healthy subjects. Urinary 8-iso-PGF(2alpha) excretion was significantly higher in CbetaSD patients than in control subjects (640+/-384 versus 213+/-43 pg/mg creatinine; P=0.0015) and correlated with plasma homocysteine (rho=0.398, P=0.0076). Similarly, urinary 11-dehydro-TXB(2) excretion was enhanced in CbetaSD (1166+/-415 versus 324+/-72 pg/mg creatinine; P=0.0015) and correlated with urinary 8-iso-PGF(2alpha) (rho=0.362, P=0.0153). Vitamin E supplementation (600 mg/d for 2 weeks) was associated with a statistically significant increase in its plasma levels (from 16.6+/-4.6 to 40.4+/-8.7 micromol/L, P=0.0002) and with reductions in 8-iso-PGF(2alpha) (from 790+/-159 to 559+/-111 pg/mg creatinine, P=0.018) and 11-dehydro-TXB(2) (from 1273+/-383 to 913+/-336 pg/mg creatinine, P=0.028). A statistically significant inverse correlation was found between urinary 8-iso-PGF(2alpha) and plasma vitamin E levels (rho=-0.745, P=0.0135). CONCLUSIONS: The results of the present study suggest that enhanced peroxidation of arachidonic acid to form bioactive F(2)-isoprostanes may represent an important mechanism linking hyperhomocysteinemia and platelet activation in CbetaSD patients. Moreover, they provide a rationale for dose-finding studies of vitamin E supplementation in this setting.

Pro12Ala substitution in the peroxisome proliferator-activated receptor-gamma2 is not associated with type 2 diabetes.

Peroxisome proliferator-activated receptor (PPAR)-gamma is a major regulator of adipogenesis and insulin sensitivity. The PPAR-gamma gene generates two isoforms through alternative splicing, PPAR-gamma1 and -gamma2, the latter having an additional stretch of 28 amino acids at its NH2-terminus in the ligand-independent activation domain. This extension renders PPAR-gamma2 more sensitive to insulin action. Since there is a Pro12Ala substitution in this domain, we tested whether it is related to type 2 diabetes or insulin resistance. Therefore, 131 type 2 diabetic patients and 312 normoglycemic control subjects were screened for the presence of the mutation and for major clinical and metabolic features. The frequency of the mutation did not differ significantly between diabetic patients and control subjects. BMI, insulin, and other metabolic and anthropometric variables were also not associated with the mutation. Although the study was carried out on a sufficiently large sample, the conclusions do not support a major role for the Pro12Ala substitution of the PPAR-gamma gene in the etiology of type 2 diabetes.

The first ambulatory screening on thromboembolism: a multicentre, cross-sectional, observational study on risk factors for venous thromboembolism.

OBJECTIVES: To assess the prevalence of risk factors for venous thromboembolism (VTE) and the prevalence of recent (<1 year) VTE [including superficial vein thrombosis (SVT), deep vein thrombosis (DVT) and pulmonary embolism (PE)] amongst patients attending general practitioner (GP) surgeries. DESIGN: Multicentre, cross-sectional, observational study. SETTING: A total of 1536 GP surgeries. PARTICIPANTS: A total of 15 180 adult, co-operative subjects, who had consulted their GP for a health disorder and signed the informed consent form. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Prevalence of known VTE risk factors graded according to importance and prevalence of recent (<1 year) VTE events (including SVT), based on interviews. RESULTS: About 1:5 patients had at least one strong risk factor and about 1:20 had at least two risk factors, with no difference between sexes. The prevalence of strong risk factors increased with age. Most were related to medical conditions: history of SVT and/or DVT/PE, heart failure and malignancy. About 3:4 women and 2:3 men had at least one moderate to weak risk factor; nearly 1:2 women and 1:3 men had at least two moderate to weak risk factors. The most common were: history of VTE, smoking, history of miscarriage, estrogen therapy, obesity, and varicose veins. Overall, 80% women and 67% men had at least one risk factor, and 50% women and 35% men had at least two risk factors. The prevalence of recent (<1 year) VTE was 3.4% in women and 2.4% in men, and increased with age. The majority of cases were SVT in both sexes (2.5% in women and 1.5% in men). CONCLUSIONS: The prevalence of risk factors for VTE amongst patients attending GP surgeries is high. GPs should bear this in mind during their daily practice.

Venous thromboembolism: which patients are truly at risk?

In clinical practice there are several conditions that are at relatively high risk of venous thromboembolism (VTE). However, not all patients included in the high risk category will actually develop VTE, and not all patients in the low risk category are protected against this eventuality. A high risk of VTE is associated with orthopedic or major surgery; a relative risk is associated with laparoscopic surgery, intermediate risk is associated, for instance, with oncology. In conclusion, individuals with deficiencies of natural anticoagulants, homozygotes due to mutation of Factor V Leiden or prothrombin and individuals with multiple risk factors may be defined as "high risk".

Pharmacological treatment and prevention of chronic venous ulcers: a review.

Chronic venous insufficiency and chronic venous ulcers represent an important medical problem, because of the high incidence and prevalence in the general population, and need to be considered as a lifelong degenerative condition, with socioeconomic consequences. Ulceration is a severe complication of the post-thrombotic syndrome, often precipitated by minor trauma. The rate of post-thrombotic syndrome varies between 20% and 100% of patients with deep vein thrombosis, mostly occurring within two years of an initial thrombotic event. This syndrome is difficult to treat, causes significant disability and reduces the quality of life. To date, there are no effective therapies of chronic venous ulcers and no definite strategies for identifying patients at risk for the development of ulceration. The role of adequate compression with elastic stockings is well recognized. Several systemic drugs have been tested for a possible effect on chronic venous ulcer healing, but none has been widely accepted as standard therapy in this setting. It has been suggested that extended oral anticoagulation should be investigated as a possible preventative measure. Waiting for the results in this field, an adequate management of anticoagulation in terms of anticoagulant intensity and duration should be recommended for the prevention of recurrent deep vein thrombosis, post-thrombotic syndrome and chronic venous ulcers.

Challenges in the prevention of venous thromboembolism in the elderly.

Aging itself is a risk factor for venous thromboembolism, and the prevalence in the elderly of additional risk factors (e.g. cancer, orthopedic surgery, immobility) increase its intrinsic risk. Many in the medical community are reluctant to prescribe anticoagulation (for primary and secondary prevention of venous thromboembolism) to their geriatric patients for the fear that bleeding complications may outweigh the benefits. A thorough analysis of the data support the concept that the under-use of heparin in primary prevention in the elderly is more related to medical beliefs than to facts. The risk of bleeding due to oral anticoagulants (secondary prevention) is greatly reduced by keeping the International Normalized Ratio (INR) values within therapeutic ranges and carefully avoiding conditions/drugs that may interfere with such treatment. The oral direct thrombin inhibitor ximelagatran has been studied for primary (hip and knee replacement surgery) and for secondary prophylaxis of venous thromboembolism, and for acute venous thromboembolism treatment. The selective factor Xa inhibitor fondaparinux has been approved for primary prophylaxis of venous thromboembolism in hip and knee replacement surgery and in hip fracture surgery. Studies on the latter drugs, where most of the patients were > 65 years of age, further show that the fear of bleeding complications due to anticoagulation in the elderly is largely unjustified.

[Caloric intake and distribution of the main nutrients in a population of obese children]. / Introito calorico e ripartizione dei principali nutrienti in una popolazione infantile obesa.

Calorie intake and the main nutrient contents were assessed in a population of 152 obese (OB) children (86 M; 66 F; age 7-11) and 153 normal weight (NW) peers (87 M; 66 F). The following method was used: a) an interview using a food dictionary to assess food intake during the 2 days prior to the study and on one holiday: and b) a weekly questionnaire. The mean food intake of OB did not exceed that of NW, but on the contrary was lower (OB: 1812.9 +/- 39.6 kcal/die; NW: 1928.5 +/- 39.4 kcal/die; p less than 0.05). The population studied consumed approximately 50% of calories as carbohydrates (CHO), 35% as fats (F) and 15% as protein (P), and no difference was noted between OB and NW. The percentage of CHO was lower than that recommended by LARN, whereas the percentages of F and P were higher. A significant increase with age was noted in F and P intake as was a significant reduction of CO. 70% of OB and 80% of NW matched or exceeded the calorie intake recommended by LARN. 30% of OB and 24% of NW consumed 30% less than the daily calorie intake recommended by LARN.

The use of antithrombotic drugs in older people.

Older individuals (subjects aged >65 years) largely contribute to the percentage deaths due to myocardial infarction (MI) and stroke. The incidence of venous thromboembolism (VTE) is also higher >65 years old patients. However, the risk of bleeding complications in patients on antithrombotic drugs increases with age and with clinical conditions, as cognitive/psychiatric diseases, traumas, hypertension, poor compliance with medications, common in the elderly. Thus the risk-benefit ratio of antithrombotics should be carefully evaluated in older individuals. To prevent the risk and the recurrence of ischemic stroke and MI in the older patients with stable/ unstable angina, MI, TIA/stroke or peripheral arterial disease, antiplatelet drugs are of choice. Aspirin is the most widely used antiplatelet drug. Clopidogrel is safer and more effective than aspirin in this respect. The combination of heparin and aspirin is the treatment of choice for unstable angina and non-Q wave MI, also in the elderly. Low molecular weight heparins (LMWHs) proved to be as effective as standard heparin in this indication. In the absence of contraindications, thrombolysis for treatment of acute MI may be considered in the elderly. For the treatment of acute venous thromboembolism (VTE), intravenous standard heparin, subcutaneous standard heparin or LMWHs are effective. Because of the limited risk/benefit ratio, thrombolytic agents are not recommended for treating deep vein thrombosis (DVT) in the elderly. They should be limited to young patients and to patients with massive pulmonary embolism (PE). For chronic treatment of VTE, warfarin is the treatment of choice (INR 2.0-3.0), also in the elderly. Because of hypersensitivity to oral anticoagulants, lower dosages of warfarin are needed in the old patient. As to prophylaxis of VTE in surgery, in subjects at low-moderate risk, or in medical patients, low-dose heparin or low-dose LMWHs are effective. As to prophylaxis of VTE in surgery in subjects at high risk, adjusted-dose heparin or high-dose LMWHs are recommended. Finally, as to prevention of stroke in patients older than 75 with atrial fibrillation (AF), warfarin is of choice.

The thromboembolic risk in giant cell arteritis: a critical review of the literature.

Giant cell arteritis is a systemic vasculitis characterized by granulomatous inflammation of the aorta and its main vessels. Cardiovascular risk, both for arterial and venous thromboembolism, is increased in these patients, but the role of thromboprophylaxis is still debated. It should be suspected in elderly patients suffering from sudden onset severe headaches, jaw claudication, and visual disease. Early diagnosis is necessary because prognosis depends on the timeliness of treatment: this kind of arteritis can be complicated by vision loss and cerebrovascular strokes. Corticosteroids remain the cornerstone of the pharmacological treatment of GCA. Aspirin seems to be effective in cardiovascular prevention, while the use of anticoagulant therapy is controversial. Association with other rheumatological disease, particularly with polymyalgia rheumatica is well known, while possible association with antiphospholipid syndrome is not established. Large future trials may provide information about the optimal therapy. Other approaches with new drugs, such as TNF-alpha blockades, Il-6 and IL-1 blockade agents, need to be tested in larger trials.

Air pollution, vascular disease and thrombosis: linking clinical data and pathogenic mechanisms.

The public health burden of air pollution has been increasingly recognized over the last decades. Following the first assessed adverse effects on respiratory diseases and lung cancer, a large body of epidemiologic and clinical studies definitely documented an even stronger association of air pollution exposure with cardiovascular mortality and morbidity, particularly related to atherothrombotic (coronary and cerebrovascular) disease. Particulate matter (PM), mainly that with lower aerodynamic diameter (fine and ultrafine PM), is responsible for the most severe effects, due to its capacity to transport toxic substances deep into the lower airways. These effects have been shown to occur not only after short-term exposure to elevated concentrations of pollutants, but even after long-term relatively low levels of exposure. Vulnerable subjects (elderly persons and those with preexisting cardiopulmonary diseases) show the highest impact. Fewer and conflicting data also suggest an association with venous thromboembolism. Although not completely elucidated, a series of mechanisms have been hypothesized and tested in experimental settings. These phenomena, including vasomotor and cardiac autonomic dysfunction, hemostatic unbalance, oxidative stress and inflammatory response, have been shown to change over time and differently contribute to the short-term and long-term adverse effects of pollution exposure. Beyond environmental health policies, crucial for improving air quality and reducing the impact of such an elusive threat to public health, the recognition and assessment of the individual risk, together with specific advice, should be routinely implemented in the strategies of primary and secondary cardiovascular prevention.