Optimal duration of low molecular weight heparin for the treatment of cancer-related deep vein thrombosis: the Cancer-DACUS Study.

PURPOSE: We evaluated the role of residual vein thrombosis (RVT) to assess the optimal duration of anticoagulants in patients with cancer who have deep vein thrombosis (DVT) of the lower limbs. PATIENTS AND METHODS: Patients with active cancer and a first episode of DVT treated with low molecular weight heparin (LMWH) for 6 months were eligible. Patients were managed according to RVT findings: those with RVT were randomly assigned to continue LMWH for an additional 6 months (group A1) or to discontinue it (group A2), and patients without RVT stopped LMWH (group B). The primary end point was recurrent venous thromboembolism (VTE) during the 1 year after disconinuation of LMWH, and the secondary end point was major bleeding. Analyses are from the time of random assignment. RESULTS: Between October 2005 and April 2010, 347 patients were enrolled. RVT was detected in 242 patients (69.7%); recurrence occurred in 22 of the 119 patients in group A1compared with 27 of 123 patients in group A2. The adjusted hazard ratio (HR) for group A2 versus A1 was 1.37 (95% CI, 0.7 to 2.5; P = .311). Three of the 105 patients in group B developed recurrent VTE; adjusted HR for group A1 versus B was 6.0 (95% CI, 1.7 to 21.2; P = .005). Three major bleeding events occurred in group A1, and two events each occurred in groups A2 and B. The HR for major bleeding in group A1 versus group A2 was 3.78 (95% CI, 0.77 to 18.58; P = .102). Overall, 42 patients (12.1%) died during follow-up as a result of cancer progression. CONCLUSION: In patients with cancer with a first DVT, treated for 6 months with LMWH, absence of RVT identifies a population at low risk for recurrent thrombotic events. Continuation of LMWH in patients with RVT up to 1 year did not reduce recurrent VTE.

Correlation between osteoporosis and cardiovascular disease.

Several evidences have shown in the last years a possible correlation between cardiovascular diseases and osteoporosis. Patients affected with osteoporosis, for example, have a higher risk of cardiovascular diseases than subjects with normal bone mass. However, the heterogeneous approaches and the different populations that have been studied so far have limited the strength of the findings. Studies conducted in animal models show that vascular calcification is a very complex mechanism that involves similar pathways described in the normal bone calcification. Proteins like BMP, osteopontin, osteoprotegerin play an important role at the bone level but are also highly expressed in the calcified vascular tissue. In particular, it seems that the OPG protect from vascular calcification and elevated levels have been found in patients with CVD. Other factors like oxidative stress, inflammation, free radicals, lipids metabolism are involved in this complex scenario. It is not a case that medications used for treating osteoporosis also inhibit the atherosclerotic process, acting on blood pressure and ventricular hypertrophy. Given the limited amount of available data, further studies are needed to elucidate the underlying mechanisms between osteoporosis and cardiovascular disease which may be important in the future also for preventive and therapeutic approaches of both conditions.

Vγ9Vδ2 T lymphocytes activation in osteoporotic patients treated with bisphosphonates.

Treatment with bisphosphonates induces differentiation and activation of Vγ9Vδ2 T lymphocytes obtained from peripheral blood showing also an antitumoral effect in both in vitro and in vivo models. Aim of the present study was to determine in vivo the effect of BPs treatment in patients affected with osteoporosis on Vγ9Vδ2 T lymphocytes. We have studied Vγ9Vδ2 T lymphocytes expansion and differentiation from PBMC obtained from osteoporotic patients treated with one of the following bisphosphonates zoledronate, alendronate, neridronate or risedronate. We have found that zoledronic acid, followed by alendronate was the most effective on reducing CM population (100%) and increasing TEM and TEMRA γδ population. Our results indicate that in vivo treatment with BPs induces Vγ9Vδ2 cells to mature toward the effector phenotype, which may induce more antiresorptive responses.

Serum 25-OH Vitamin D in relation to Bone Mineral Density and Bone Turnover.

It is unclear which vitamin D status is optimal for bone health. In this study, we aimed to assess cutoffs of 25-hydroxyvitamin D (25OHD) derived by the literature (20, 25, or 30 ng/mL) in relation to bone turnover and bone mineral density (BMD). Serum 25OHD, PTH, osteocalcin, bone alkaline phosphatase, and C-telopeptide were measured in 274 consecutive postmenopausal women. BMD of the lumbar spine (L1-L4) and of femoral neck were also evaluated. 50 patients had normal BMD, while 124 had osteopenia and 100 had osteoporosis. 37.6%, 56.2%, and 70.8% subjects had serum 25OHD lower than 20, 25, or 30 ng/mL, respectively. No differences in bone turnover markers were found when comparing patients with low 25OHD defined according to the different cutoffs. However, a cutoff of 25 ng/mL appeared to differentiate better than a cutoff of 30 ng/mL in those subjects with reduced femoral neck BMD. The PTH plateau occurred at 25OHD levels of 26-30 ng/mL. In conclusion, vitamin D deficiency is common in Sicilian postmenopausal women and it may be associated with low BMD and increased bone turnover markers. Further studies are needed to better define the right cutoff for normal vitamin D levels in postmenopausal women.

Habitual fish intake and clinically silent carotid atherosclerosis.

BACKGROUND: Fish consumption is recommended as part of a healthy diet. However, there is a paucity of data concerning the relation between fish consumption and carotid atherosclerosis. We investigated the association between habitual fish consumption and asymptomatic carotid atherosclerosis, defined as the presence of plaques and/or increased intima-media thickness (≥ 0.90 mm), in non-diabetic participants. METHODS: Nine hundred-sixty-one (range of age: 18-89 yrs; 37.1% males) adult participants without clinically known atherosclerotic disease were randomly recruited among the customers of a shopping mall in Palermo, Italy, and cross-sectionally investigated. Each participant answered a food frequency questionnaire and underwent high-resolution ultrasonographic evaluation of both carotid arteries. Routine laboratory blood measurements were obtained in a subsample of 507 participants. RESULTS: Based on habitual fish consumption, participants were divided into three groups: non-consumers or consumers of less than 1 serving a week (24.0%), consumers of 1 serving a week (38.8%), and consumers of ≥ 2 servings a week (37.2%). Age-adjusted prevalence of carotid atherosclerosis (presence of plaques or intima media thickness ≥ 0.9 mm) was higher in the low fish consumption group (13.3%, 12.1% and 6.6%, respectively; P = 0.003). Multivariate analysis evidenced that carotid atherosclerosis was significantly associated with age (OR = 1.12; 95% CI = 1.09-1.14), hypertension on pharmacologic treatment (OR = 1.81; 95% CI = 1.16-2.82), and pulse pressure (OR = 1.03; 95% CI = 1.01-1.04), while consuming ≥2 servings of fish weekly was protective compared with the condition of consumption of <1 serving of fish weekly (OR = 0.46; 95% CI = 0.26-0.80). CONCLUSIONS: High habitual fish consumption seems to be associated with less carotid atherosclerosis, though adequate interventional trials are necessary to confirm the role of fish consumption in prevention of cardiovascular disease.

The endocrine response to severe burn trauma.

The endocrine system is frequently altered after a major burn trauma. Besides the endocrine response to stress characterized by hypercortisolism, several hypothalamus-hypophysis-target gland axes are rapidly perturbed within a few days. These alterations can persist in the long term and deserve an appropriate treatment. Disturbances in water clearance and glucidic metabolism are also common and need to be diagnosed and corrected to decrease morbidity in such patients. Bone and mineral metabolism is deeply compromised and requires correction of mineral abnormalities in order to improve symptoms and prevent bone loss. No large prospective and/or intervention trials are available to date to elaborate age-related, evidence-based recommendations to monitor and treat burn-related endocrine alterations.

Psychological and behavioural factors associated with long-term weight maintenance after a multidisciplinary treatment of uncomplicated obesity.

Obesity is a multifactorial syndrome and the likelihood of success of a medical nutritional treatment (MNT) over the long term is low. As psychological and behavioural factors have an important role in both pathogenesis and the treatment of obesity, these issues were investigated in individuals with obesity who reported a long-term success or a failure in terms of weight loss following a MNT. Eighty-eight individuals of an original cohort of 251 subjects were re-evaluated 10 years after a MNT with cognitive-behavioural approach for uncomplicated obesity. Fifty-three participants were classified as failure (body weight change ≥0.5 kg) and 35 as a success (10-year body weight change <0.5 kg) of the MNT. Prior to the beginning of the weight-management program, both the Dieting Readiness Test (DRT) and the Hospital Anxiety and Depression Scale (HADS) were administered. At a 10-year follow-up after the MNT, self-reported questionnaires were administered: quality of life was assessed by the Obesity Related Well-Being (ORWELL 97) questionnaire, eating attitudes and behaviours by the Eating Disorder Examination Questionnaire (EDE-Q), the Binge Eating Scale (BES) investigated the presence and severity of binge eating and the Symptom Checklist (SCL 90-R) was used to identify the psychopathological distress. The scores of the ORWELL 97 items concerning symptoms (P = 0.005), discomfort (P = 0.03) and the total score (P = 0.02) were significantly lower in the success group. The depression score of the HADS was positively correlated with the percentage of body weight change observed 10 years after the MNT (r = 0.22; P = 0.045). The scores of the shape concern (EDE-Q) (r = 0.35; P = 0.013) and of the discomfort (ORWELL 97) (r = 0.36; P = 0.012) were significantly correlated with the percentage of body weight change 10 years after the MNT. In conclusion, this study is in agreement with the possibility that the psychological quality of life is associated even with modest amounts of weight loss in the long run. Further research should support identifying successful predictors of weight loss.

Prevalence and predictors of left ventricular hypertrophy in patients with hypertension and normal electrocardiogram.

BACKGROUND: Electrocardiography (ECG) has low sensitivity for detecting left ventricular hypertrophy (LVH), while echocardiography cannot be routinely performed. DESIGN/METHODS: In this study we evaluate the prevalence of LVH and diastolic dysfunction in hypertensive patients with normal ECG. We excluded patients with cardiovascular (CV) diseases, diabetes, chronic kidney disease, or presenting ECG-LVH or other ECG anomalies. The enrolled 440 hypertensive patients underwent echocardiographic examination (Acuson Sequoia 512); LV mass was indexed by body surface area (LVMI) and LVH was defined as LVMI >125 g/m(2) in men and >110 g/m(2) in women. Diastolic function was evaluated by mitral inflow and tissue Doppler imaging (TDI). RESULTS: The prevalence of LVH was 8.18% (95% confidence interval [CI] 5.97-11.1%). Multiple regression analysis showed that the only variable independently associated with LVH was duration of hypertension (p < 0.001). The receiver operating characteristic (ROC) curve showed that duration of hypertension was a powerful predictor of LVH, with an area under the curve (AUC) of 0.878 and p < 0.0001. Further, in patients with LVH the mean difference of LVMI from the cut-off value for LVH was 12.3 ± 9.19 g/m(2). Diastolic dysfunction, defined as early diastolic myocardial velocity (Em) <0.08 m/s, was detected only in 3.2% of patients. CONCLUSIONS: The prevalence of LVH among hypertensive patients with normal ECG, free of diabetes and of CV diseases is low; moreover, patients with echocardiographic LVH presented LVMI values that identified mild LVH. Few cases of impaired diastolic function were registered. We suggest that in hypertensive patients with such characteristics the echocardiographic examination should be reserved to those who present with higher duration of hypertension.

Chronic spontaneous urticaria: an autoimmune disease? A revision of the literature.

The cause of chronic spontaneous urticaria has been an enigma for decades, but the recognition of functional autoantibodies in some patients with the spontaneous chronic urticaria has opened up a new concept of autoimmune urticaria. Clinical and laboratory features are in keeping with an autoimmune aetiology for many patients with otherwise inexplicable disease, but there is still debate about the importance of functional autoantibodies in the disease pathogenesis, how to test them and the clinical implications for treatment and prognosis. This review will look at the evidence for there being an autoimmune subset of urticaria, the strengths and weaknesses of the available tests in current use.

Clinical course of rhinitis and changes in vivo and in vitro of allergic parameters in elderly patients: a long-term follow-up study.

Changes in rhinitis symptom severity tend to decrease with aging, but whether the decrease is associated with allergic skin test reactivity, serum total and specific IgE, and nasal eosinophils or determined only by aging is poorly understood. The aim of the study was to analyze sensitivity in vivo and in vitro some 15 years after primary testing, skin prick test (SPT), serum total and specific IgE, ratio sIgE/tIgE, and nasal eosinophils in order to evaluate changes due to age and changes due to the severity of rhinitis symptoms. One hundred and eight rhinitis patients who had been investigated in 1995 were re-interviewed and their current allergy re-assessed after a follow-up of 15 years. All patients were SPT with eight common allergens in the area of Palermo (Italy). Rhinitis symptoms tended, on average, to have become milder at the follow-up. All parameters examined showed a decreasing trend in older age groups over the period between the two investigations. Rhinitis symptoms tend to become milder and the allergic parameters both in vivo and in vitro usually decrease in the long run; however, the changes in rhinitis symptoms appear to be related to changes in the nasal eosinophils, independently of SPT and serum-specific IgE.

Effects of hypocaloric diets with different glycemic indexes on endothelial function and glycemic variability in overweight and in obese adult patients at increased cardiovascular risk.

BACKGROUND & AIMS: The role of glycemic index of the diet in glucose control and cardiovascular prevention is still not clear. The aim of this study was to determine the effects of hypocaloric diets with different glycemic indexes and glycemic loads on endothelial function and glycemic variability in nondiabetic participants at increased cardiovascular risk. METHODS: Forty nondiabetic obese participants were randomly assigned to a three-month treatment with either a low glycemic index (LGI; n=19) or high glycemic index (HGI; n=21) hypocaloric diet with similar macronutrient and fiber content. Endothelial function was measured as flow-mediated dilatation (FMD) of the brachial artery before and after dieting. In addition, 48-h continuous subcutaneous glucose monitoring was done before and after dieting in a subgroup of 24 participants. RESULTS: The amount of weight loss after dieting was similar in both groups. The glycemic index of the diet significantly influenced the FMD (P<0.005). In particular, the change of FMD was 2.3±2.6% following the LGI diet, and -0.9±3.6% after the HGI diet (P<0.005). The mean 48-h glycemia decreased significantly after dietary treatment (P<0.05), but no significant effect of the glycemic index of the diet on results was observed. The glycemic index of the diet significantly influenced the 48-h glycemic variability measured as coefficient of variability (CV%; P<0.001). The CV% decreased after the LGI diet (from 23.5 to 20.0%) and increased after the HGI diet (from 23.6 to 26.6%). The change in percentage of FMD was inversely correlated with the change in the 48-h glycemic CV% (r=-0.45; P<0.05). CONCLUSIONS: Endothelial function and glycemic variability ameliorate in association with the adherence to an LGI hypocaloric diet in nondiabetic obese persons. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN56834511.

Endothelial function and other biomarkers of cardiovascular risk in frequent consumers of street food.

BACKGROUND & AIMS: Street food (SF) is defined as out-of-home food consumption, and generally consists of energy dense meals rich in saturated fats, and poor in fibers, vitamins and anti-oxidants. Though SF consumption may have unfavorable metabolic and cardiovascular effects, its possible association with endothelial function has not been considered. METHODS: Participants were recruited among those who took part in a previous study of ours, done in Palermo, Italy, which investigated the association between consumption of SF and health in 1002 people. In that study, a score of SF consumption was obtained by categorizing each of ten foods consumed less than or more than once a month (0 = never consumed, 1 = once a month or less, 2 = more than once a month; thus, the sum of single scores could range from 0 to 20). Based on the interquartile values of SF score distribution, in the present study we included low SF consumers, defined on the basis of the first interquartile SF score range (range: 0-1), and high SF consumers, who were those in the forth interquartile range of the SF score (range: 7-20). The group of low SF consumers had 12 participants (median value of SF score: 1; range: 0-1), that of high SF consumers had 13 (median value of SF score: 11; range: 10-16). The brachial artery flow-mediated dilatation (FMD), a measure of endothelial function, and other cardiovascular biomarkers were investigated. RESULTS: High SF consumers had higher BMI (P = 0.026), larger waist circumference (P = 0.041), higher levels of cholesterol (P = 0.013) and uric acid serum concentrations (P = 0.002) compared with low SF consumers. The high SF consumers had a significantly lower FMD (5.4 ± 2.1 versus 8.8 ± 2.8%; ANCOVA with BMI and waist circumpherence as covariates: P = 0.025) than the high consumers. Other cardiovascular biomarkers did not significantly differ between the two groups. CONCLUSIONS: This study suggests that high SF consumption in Palermo may be associated with endothelial dysfunction in healthy people, probably indicating that this category of foods should be limited, especially in people at high cardiovascular risk.

New insight into immunity and immunopathology of Rickettsial diseases.

Human rickettsial diseases comprise a variety of clinical entities caused by microorganisms belonging to the genera Rickettsia, Orientia, Ehrlichia, and Anaplasma. These microorganisms are characterized by a strictly intracellular location which has, for long, impaired their detailed study. In this paper, the critical steps taken by these microorganisms to play their pathogenic roles are discussed in detail on the basis of recent advances in our understanding of molecular Rickettsia-host interactions, preferential target cells, virulence mechanisms, three-dimensional structures of bacteria effector proteins, upstream signalling pathways and signal transduction systems, and modulation of gene expression. The roles of innate and adaptive immune responses are discussed, and potential new targets for therapies to block host-pathogen interactions and pathogen virulence mechanisms are considered.

Malignant tumor-like gastric lesion due to Candida albicans in a diabetic patient treated with cyclosporin: a case report and review of the literature.

The gastrointestinal tract of healthy individuals is colonized by hundreds of saprophytes and mycetes, especially the Candida species, are habitual ones. Under certain conditions, the fungal flora may overgrow, resulting in lesions of the digestive mucosa which, rarely, can have a local diffusion and/or spread to the lympho-hematogenous system. Mycotic infections of the stomach can sometimes look like benign gastric ulcers. Here, we present the case report of a woman, aged 64, who presented with type II diabetes mellitus and psoriasis, on chronic treatment with cyclosporin A and with endoscopic evidence of an ulcerated, vegetating gastric lesion secondary to Candida albicans infection. Although strongly suggestive of malignancy, it completely healed after cyclosporin withdrawal and the administration of oral antifungal drugs.

Significance of persistence of antibodies against Leishmania infantum in Sicilian patients affected by acute visceral leishmaniasis.

The background of this article is as follows: Few data are available about the persistence of serum-specific IgG antibodies to L. infantum after acute VL. The objective of this article is to evaluate the persistence of antibodies against L. infantum in patients healed from acute VL, and the kinetic of the same antibodies observed in 2 cases of VL relapse and 2 cases of resistance to therapy. The methods which we used to obtain our objective are the following: 55 apparently immunocompetent, HIV-negative patients were examined for antibodies to L. infantum by IFAT over 14 years period, and we got the following results: Serum-specific IgG antibodies titers decrease slowly, but constantly. In the patients with a diagnosis of VL relapse, the kinetic of antibodies was characterized by an initial reduction, and a subsequent antibody levels rapidly increase, while in the patients with a clinical and parasitological diagnosis of VL not responding to specific therapy, we demonstrated persistent high level of antibodies to L. infantum. Finally, we conclude that specific antibodies to L. infantum might persist for many years, and decrease slowly, but steadily. The persistence of these specific antibodies is not related to poor therapeutic response or prognosis, but an acute increase in their levels might be a sentinel of a VL relapse, while persistence of high antibody levels could suggest a resistance to therapy.

Heat shock protein-60 and risk for cardiovascular disease.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. There is growing evidence that molecular chaperones, many of which are heat shock proteins HSPs, are involved in CVD pathogenesis. In this review we focus on HSP60, the human mitochondrial chaperone that also displays extramitochondrial and extracellular functions. HSP60 is typically cytoprotective but a number of stress conditions determine its conversion to a potentially toxic molecule for cells and tissues. We present illustrative examples of specific subtypes of CVD where HSP60 is implicated in the initiation and/or progression of disease. The data not only indicate a pathogenic role for HSP60 but also its potential as a biomarker with applications for diagnosis, assessing prognosis and response to treatment, as well as for preventing and treating CVD.

Predicting efficacy and toxicity in the era of targeted therapy: focus on anti-EGFR and anti-VEGF molecules.

The treatment of solid malignancies includes various target drugs, such as monoclonal antibodies and tyrosine kinase inhibitors, which exert their effect alone or in combination with chemotherapy. The main part of these molecules have a target on proteins of EGFR and VEGF pathways. The particular toxicity profile and the financial impact, deriving from the application of these agents in cancer treatment, prompted a lot of researches to define predictive factors of their efficacy. Various biomarker were identified among the components of the targeted pathways. However just few studies allowed to identify specific factors to predict the toxicity of these drugs. In this review EGFR and VEGF-related pathways are described, most relevant clinical findings about target therapy applications are exposed and the clinical impact of predictive factors of efficacy and toxicity are discussed.

"European panel on low density lipoprotein (LDL) subclasses": a statement on the pathophysiology, atherogenicity and clinical significance of LDL subclasses.

Aim of the present Consensus Statement is to provide a comprehensive and up to-date document on the pathophysiology, atherogenicity and clinical significance of low density liproproteins (LDL) subclasses. We sub-divided our statement in 2 sections. section I discusses the pathophysiology, atherogenicity and measurement issues, while section II is focused on the effects of drug and lifestyle modifications. Suggestions for future research in the field are highlighted at the end of section II. Each section includes Conclusions.