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.

Impact of lifestyle on metabolic syndrome in apparently healthy people.

Parallel to the increase in obesity, the prevalence of metabolic syndrome (MetS) is continually increasing, with increased risk of diabetes and cardiovascular atherosclerosis diseases. Despite the importance of this public health problem, the relative impact of diet and physical activity on MetS prevalence has yet to be established. We investigated the association between lifestyle, in terms of both habitual dietary pattern and physical activity, and MetS in a cohort of adults without known diabetes and atherosclerotic cardiovascular disease. Four hundred seventy-seven randomly selected adult participants were cross-sectionally investigated. Each participant answered a food frequency questionnaire and a questionnaire on physical activity, and underwent routine laboratory blood measurements. MetS was identified in 24.7% of the cohort. Dietary patterns were not significantly different (P = 0.31) between the groups (with or without MetS). The habitual physical activity level was significantly lower (P = 0.011) in the group with MetS. In particular, the prevalence of sedentary participants was 58.1% in the group with MetS, and 43.9% in the group without MetS. Multivariate analysis revealed that MetS was associated with age (OR = 1.06, 95% CI 1.03-1.08) and physical activity level (light vs. sedentary: OR = 0.53, 95% CI 0.32-0.87; moderate/heavy vs. sedentary: OR = 0.31, 95% CI 0.13-0.75). This study suggests that inadequate physical activity level is associated with MetS. Our results are therefore consonant with the notion of healthier lifestyle changes to counteract the epidemic of diabetes and cardiovascular disease, though adequate interventional trials will be needed in high-risk populations.

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.

Immunotherapy for recurrent ovarian cancer: a further piece of the puzzle or a striking strategy?

INTRODUCTION: Treatment of ovarian cancer has been long standardized with the inclusion of surgery and chemotherapy based on platinum and taxanes, this strategy reaching high remission rates. However, when this treatment fails, further options are available with little benefit. Since ovarian cancer has specific immunologic features, actually immunotherapy is under evaluation to overcome treatment failure in patients experiencing recurrence. AREAS COVERED: Immunogenicity of ovarian cancer and its relationship with clinical outcomes is briefly reviewed. The kinds of immunotherapeutic strategies are summarized. The clinical trials investigating immunotherapy in recurrent ovarian cancer patients are reported. EXPERT OPINION: The results of these clinical trials about immunotherapy are interesting, but little clinical benefit has been achieved until now. For this reason, we could conclude that immunotherapy is quite different from other treatment options and it could change the global approach for recurrent ovarian cancer treatment. However, to date only fragmentary findings are available to define the real role of immunotherapy in this setting.

Habitual street food intake and subclinical carotid atherosclerosis.

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 antioxidants. Though SF consumption may have unfavorable metabolic and cardiovascular effects, its possible association with atherosclerosis has not been considered. The association between habitual SF consumption and asymptomatic carotid atherosclerosis, defined as the presence of plaques and/or increased intima-media thickness, was therefore investigated. One thousand thirty-five randomly selected adult participants without known diabetes and atherosclerotic cardiovascular diseases were cross-sectionally investigated in Palermo, Italy. Each participant answered a food frequency questionnaire and underwent high-resolution ultrasonographic evaluation of both carotid arteries. Laboratory blood measurements were obtained in a subsample of 541 participants. A score of SF consumption was obtained by categorizing each of ten SFs consumed more or less than once a month. Participants were divided into three classes based on the tertiles of SF score distribution. Age, gender distribution, body mass index (BMI), prevalence of hypertension and of clinically silent carotid atherosclerosis (I tertile 20.8 %, II tertile 19.7 %, III tertile 19.0 %; P = 0.85) were not significantly different among the three groups. Clinically silent carotid atherosclerosis was independently associated with age, gender and hypertension. The score of SF consumption was significantly correlated with BMI (r = 0.10; P = 0.04), uric acid (r = 0.16; P = 0.002) and high-density lipoproteins-cholesterol (r = -0.13; P = 0.009) blood concentrations. In conclusion, this study suggests that SF consumption is not associated with clinically silent carotid atherosclerosis. However, given the association of SF consumption with other cardiovascular risk factors, caution requires that this category of food should be limited in patients at high cardiovascular risk.

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.

Impact of chronic diuretic treatment on glucose homeostasis.

BACKGROUND: The use of diuretics for hypertension has been associated with unfavorable changes in cardiovascular risk factors, such as uric acid and glucose tolerance, though the findings in the literature are contradictory. METHODS: This study investigated whether diuretic use is associated with markers of metabolic and cardiovascular risk, such as insulin-resistance and uric acid, in a cohort of adults without known diabetes and/or atherosclerotic cardiovascular disease. Nine hundred sixty-nine randomly selected participants answered a questionnaire on clinical history and dietary habits. Laboratory blood measurements were obtained in 507 participants. RESULTS: Previously undiagnosed type 2 diabetes was recognized in 4.2% of participants who were on diuretics (n = 71), and in 2% of those who were not (n = 890; P = 0.53). Pre-diabetes was diagnosed in 38% of patients who were on diuretics, and in 17.4% (P < 0.001) of those who were not. Multivariate analysis showed that insulin-resistance (HOMA-IR) was associated with the use of diuretics (P = 0.002) independent of other well-known predisposing factors, such as diet, physical activity, body mass index, and waist circumference. The use of diuretics was also independently associated with fasting plasma glucose concentrations (P = 0.001) and uric acid concentrations (P = 0.01). CONCLUSIONS: The use of diuretics is associated with insulin-resistance and serum uric acid levels and may contribute to abnormal glucose tolerance.

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.

Osteonecrosis of the jaws in patients assuming oral bisphosphonates for osteoporosis: a retrospective multi-hospital-based study of 87 Italian cases.

BACKGROUND: Bisphosphonates (BPs) are currently the chief drugs for the prevention/treatment of osteoporosis; one of their adverse effects is the osteonecrosis of the jaw (BRONJ). The primary endpoints of this multi-center cross-sectional study are: i) an observation of the clinical features of BRONJ in 87 osteoporotic, non-cancer patients; and ii) an evaluation of their demographic variables and comorbidities. METHODS: 87 BRONJ patients in therapy for osteoporosis with BPs from 8 participating clinical Italian centers were consecutively identified and studied. After BRONJ diagnosis and staging, comorbidities and data relating to local and drug-related risk factors for BRONJ were collected. RESULTS: 77/87 (88.5%) patients in our sample used alendronate as a BP type; the duration of bisphosphonate therapy ranged from 2 to 200 months, and 51.7% of patients were in treatment for ≤ 38 months (median value). No comorbidities or local risk factors were observed in 17 (19.5%) patients, indicating the absence of cases belonging to BRONJ forms triggered by surgery. BRONJ localization was significantly associated with age: an increased risk of mandible localization (p=0.002; OR=6.36, 95%CI=[1.89; 21.54]) was observed for those over 72 yrs. At multivariate analysis, the increased risk of BRONJ in the mandible for people over 72 yrs (OR'=6.87, 95%CI=[2.13; 2.21]) was confirmed for a BP administration >56 months (OR'=4.82, 95%CI=[2.13; 22.21]). CONCLUSION: Our study confirms the fundamental necessity of applying protocols of prevention in order to reduce the incidence of BRONJ in osteoporotic, non-cancer patients in the presence of comorbidities and/or local risk factor as well as, less frequently, in their absence.

Osteoporosis, jawbones and periodontal disease

The association between osteoporosis and jawbones remains an argument of debate. Both osteoporosis and periodontal diseases are bone resorptive diseases; it has been hypothesized that osteoporosis could be a risk factor for the progression of periodontal disease and vice versa. Hypothetical models linking the two conditions exist: in particular, it is supposed that the osteoporosis-related bone mass density reduction may accelerate alveolar bone resorption caused by periodontitis, resulting in a facilitated periodontal bacteria invasion. Invading bacteria, in turn, may alter the normal homeostasis of bone tissue, increasing osteoclastic activity and reducing local and systemic bone density by both direct effects (release of toxins) and/or indirect mechanisms (release of inflammatory mediators). Current evidence provides conflicting results due to potential biases related to study design, samples size and endpoints. The aim of this article is to review and summarize the published literature on the associations between osteoporosis and different oral conditions such as bone loss in the jaws, periodontal diseases, and tooth loss. Further well-controlled studies are needed to better elucidate the inter-relationship between systemic and oral bone loss and to clarify whether dentists could usefully provide early warning for osteoporosis risk (AU)

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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.

A comparison between two different in vitro basophil activation tests for gluten- and cow's milk protein sensitivity in irritable bowel syndrome (IBS)-like patients.

BACKGROUND: The diagnosis of food hypersensitivity (FH) in adult patients with gastrointestinal symptoms, beyond the immediate IgE-mediated clinical manifestations, is very often difficult. The aims of our study were to: 1) evaluate the frequency of FH in patients with irritable bowel syndrome (IBS)-like clinical presentation; and 2) compare the diagnostic accuracy of two different methods of in vitro basophil activation tests. METHODS: Three hundred and five patients (235 females, age range 18-66 years) were included and underwent a diagnostic elimination diet and successive double-blind placebo-controlled (DBPC) challenges. Two different methods of in vitro basophil activation tests (BAT) (CD63 expression after in vitro wheat or cow's milk proteins stimulation) were evaluated: one was performed on separated leukocytes, and the other on whole blood. RESULTS: Ninety patients of the 305 studied (29.5%) were positive to the challenges and were diagnosed as suffering from FH. BAT on separate leukocytes showed a sensitivity of 86% and a specificity of 91% in FH diagnosis. BAT on whole blood showed a sensitivity of 15%-20% and a specificity of 73% in FH diagnosis (p<0.0001 compared to the other method). CONCLUSIONS: About one third of the IBS patients included in the study were suffering from FH and were cured on the elimination diet. The BAT based on CD63 detection on whole blood samples did not work in FH diagnosis and showed a significantly lower sensitivity, specificity and diagnostic accuracy than the assay based on separated leukocytes.

Osteoporosis, jawbones and periodontal disease.

The association between osteoporosis and jawbones remains an argument of debate. Both osteoporosis and periodontal diseases are bone resorptive diseases; it has been hypothesized that osteoporosis could be a risk factor for the progression of periodontal disease and vice versa. Hypothetical models linking the two conditions exist: in particular, it is supposed that the osteoporosis-related bone mass density reduction may accelerate alveolar bone resorption caused by periodontitis, resulting in a facilitated periodontal bacteria invasion. Invading bacteria, in turn, may alter the normal homeostasis of bone tissue, increasing osteoclastic activity and reducing local and systemic bone density by both direct effects (release of toxins) and/or indirect mechanisms (release of inflammatory mediators). Current evidence provides conflicting results due to potential biases related to study design, samples size and endpoints. The aim of this article is to review and summarize the published literature on the associations between osteoporosis and different oral conditions such as bone loss in the jaws, periodontal diseases, and tooth loss. Further well-controlled studies are needed to better elucidate the inter-relationship between systemic and oral bone loss and to clarify whether dentists could usefully provide early warning for osteoporosis risk.

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.

Unusual presentation of ruptured descending thoracic aortic aneurysm.

We here report a very unusual presentation of ruptured thoracic aortic aneurysm. In a 50-year-old patient, almost asymptomatic and in stable clinical conditions, the chest radiograph and computed tomography scan revealed a right-sided rupture of a previously undiagnosed thoracic aortic aneurysm. The patient was treated successfully with an emergency surgical procedure.