Predictive value of VEGF gene polymorphisms for metastatic colorectal cancer patients receiving first-line treatment including fluorouracil, irinotecan, and bevacizumab

Purpose  

The aim of this study is to evaluate the influence of germline vascular endothelial growth factor (VEGF) gene polymorphisms (VGPs) on the efficacy of the anti-VEGF antibody bevacizumab (Bev) in metastatic colorectal cancer (MCRC) patients.     

Changing epidemiology of HCV and HBV infections in Northern Italy: a survey in the general population

AIM: To evaluate the hepatitis B virus (HBV) and the hepatitis C virus (HCV) epidemiology in the general population of Northern Italy, a cohort of 965 subjects, all residents (including 47 immigrants), were anonymously tested for HBV and HCV infections. MATERIAL AND METHODS: Serum samples were assayed for anti-HCV and anti-HBV markers by enzyme-linked immunosorbent assay and for HCV-RNA by polymerase chain reaction, and the positive cases were genotyped. HBsAg-positive cases were assayed for HBeAg/anti-HBe, whereas HBsAg negatives were tested for both anti-HBc and anti-HBs. RESULTS: The overall prevalence of anti-HCV was 2.6%, with a bimodal distribution characterized by the highest prevalence (12%) in subjects over 75 years old. None of the subjects under 25 years old was anti-HCV positive. Anti-HCV positivity was similar in males and females (2.4% vs. 2.7%). HCV-RNA was positive in 40% of cases and genotype 1 was the most common. The HBsAg prevalence was 1%, with a significant difference according to country of origin (0.8% in Italian subjects vs. 6.4% in immigrants, P=0.01). HBsAg positivity increased significantly with age (R2=0.57, P<0.02). The overall percentages for the prevalence of isolated anti-HBs, anti-HBs+/anti-HBc+, and isolated anti-HBc were 23.8%, 8.4%, and 4.2%, respectively. CONCLUSIONS: Our study provides a new picture of HCV and HBV epidemiology in Northern Italy, with these features: (1) a cohort effect showing a reduction of HCV infection in the elderly, possible due to age-related mortality; (2) an unchanged overall prevalence of HBV infection, despite continuing immigration of subjects from endemic countries.     

Prevalence of vertebral fractures in men with acromegaly

CONTEXT: Data on osteoporotic fractures in acromegaly are limited. An increased prevalence of radiological vertebral fractures was already observed in postmenopausal women with active acromegaly. It is unknown whether this observation may reflect a more general increased risk of fractures in acromegaly. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at referral centers. PATIENTS AND CONTROL SUBJECTS: Subjects included 40 males with acromegaly (25 patients with controlled disease and 15 patients with active disease) and 31 control males, with age and gonadal status comparable with the patients. INTERVENTIONS: Evaluation of vertebral fractures (quantitative morphometric analysis) and bone mineral density (BMD) at lumbar spine and total hip (dual energy X-ray absorptiometry) was done. MAIN OUTCOME MEASURE: Vertebral fractures were assessed. RESULTS: Although BMD was not significantly different between acromegalic patients and control subjects, the prevalence of vertebral fractures was higher in acromegalic patients as compared with the control subjects (57.5 vs. 22.6%; chi(2): 8.7; P = 0.003). Fractured and nonfractured acromegalic patients showed no significant difference in age and BMD Z-score. However, acromegalic patients with fractures had serum IGF-I values significantly higher and duration of active disease significantly longer with respect to patients without fractures. Moreover, patients with fractures showed significantly longer untreated hypogonadism as compared with patients without fractures. In a multivariate logistic regression analysis, the duration of active acromegaly was the only risk factor significantly correlated with the occurrence of fractures (odds ratio 1.1, confidence interval 1.04-1.6). CONCLUSIONS: This study reports for the first time a high prevalence of osteoporotic vertebral fractures in an unselected acromegalic male population generally considered at low risk of osteoporosis, suggesting that complicated osteoporosis is an important comorbidity of acromegaly.     

HIV-associated immune activation: from bench to bedside

HIV infection is associated with a state of chronic, generalized immune activation that has been shown in many studies to be a key predictor of progression to AIDS. Consistent with this model, nonpathogenic SIV infections of natural hosts, such as the sooty mangabeys, are characterized by low levels of immune activation during the chronic phase of infection. The molecular, cellular, and pathophysiological mechanisms underlying the HIV-associated immune activation are complex and still poorly understood. There is, however, growing consensus that both viral and host factors contribute to this phenotype, with emphasis on the role played by the mucosal immune dysfunction (and consequent microbial translocation) as well as the pattern of in vivo-infected CD4(+) T cells. The observation that antiretroviral therapy (ART)-induced suppression of HIV replication does not fully resolve immune activation provided the rationale for a number of exploratory studies of potential immune modulatory treatments to be used in HIV-infected individuals in addition to standard ART. This review provides an update on the causes and consequences of the HIV-associated immune activation, and a summary of the immune modulatory approaches that are currently under clinical investigation.     

Incidence and prognosis of intraabdominal hypertension in a mixed population of critically ill patients: a multiple-center epidemiological study

OBJECTIVE: Intraabdominal hypertension is associated with significant morbidity and mortality in surgical and trauma patients. The aim of this study was to assess, in a mixed population of critically ill patients, whether intraabdominal pressure at admission was an independent predictor for mortality and to evaluate the effects of intraabdominal hypertension on organ functions. DESIGN: Multiple-center, prospective epidemiologic study. SETTING: Fourteen intensive care units in six countries. PATIENTS: A total of 265 consecutive patients admitted for >24 hrs during the 4-wk study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Intraabdominal pressure was measured twice daily via the bladder. Data recorded on admission were the patient demographics with Simplified Acute Physiology Score II, Acute Physiology and Chronic Health Evaluation II score, and type of admission; during intensive care stay, Sepsis-Related Organ Failure Assessment score and intraabdominal pressure were measured daily together with fluid balance. Nonsurvivors had a significantly higher mean intraabdominal pressure on admission than survivors: 11.4 +/- 4.8 vs. 9.5 +/- 4.8 mm Hg. Independent predictors for mortality were age (odds ratio, 1.04; 95% confidence interval, 1.01-1.06; p = .003), Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.1; 95% confidence interval, 1.05-1.15; p < .0001), type of intensive care unit admission (odds ratio, 2.5 medical vs. surgical; 95% confidence interval, 1.24-5.16; p = .01), and the presence of liver dysfunction (odds ratio, 2.5; 95% confidence interval, 1.06-5.8; p = .04). The occurrence of intraabdominal hypertension during the intensive care unit stay was also an independent predictor of mortality (relative risk, 1.85; 95% confidence interval, 1.12-3.06; p = .01). Patients with intraabdominal hypertension at admission had significantly higher Sepsis-Related Organ Failure Assessment scores during the intensive care unit stay than patients without intraabdominal hypertension. CONCLUSIONS: Intraabdominal hypertension on admission was associated with severe organ dysfunction during the intensive care unit stay. The mean intraabdominal pressure on admission was not an independent risk factor for mortality; however, the occurrence of intraabdominal hypertension during the intensive care unit stay was an independent outcome predictor.     

Late motor recovery is influenced by muscle tone changes after stroke

OBJECTIVES: To evaluate the time course of motor recovery in a poststroke period ranging from 2 to 6 months and its correlation with both the severity of motor deficit and the muscle tone disturbances (flaccidity or spasticity) of the affected limbs. DESIGN: Prospective cohort study. SETTING: A comprehensive rehabilitation hospital. PARTICIPANTS: Forty consecutive stroke patients (21 men, 19 women) with first ischemic stroke who met the inclusion criteria. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Change in motor deficit as evaluated by the Adams Hemispheric Stroke Scale. RESULTS: Stepwise regression analysis indicated that the most significant factors influencing motor recovery were the time elapsed since stroke and muscle tone. CONCLUSIONS: Rehabilitation of stroke patients is more effective in the first months after the event rather than later, considering the significant correlation observed between motor recovery and time elapsed since stroke. Flaccid patients appear to need 3 months or more before reaching the final plateau, because motor recovery occurs later and/or proceeds more slowly, whereas outcomes for spastic patients with spasticity appears to occur in the first months after stroke.     

Nonalcoholic steatohepatitis: recent advances from experimental models to clinical management

A condition defined as nonalcoholic fatty liver disease (NAFLD) is frequently found in humans. Deemed as a benign condition until recently, more emphasis is now put on the potential harmful evolution of the inflammatory form, that is, nonalcoholic steatohepatitis (NASH), toward end-stage liver disease. This review highlights the major morphologic and pathophysiological features of NASH. The link between experimental biochemical findings in animal models and clinical and therapeutic approaches in humans is discussed. Once all the other causes of persistent elevation of serum transaminase levels have been excluded, the diagnosis of NASH can be only confirmed by liver histology. Other noninvasive diagnostic tools, however, are being investigated to assess specific subcellular functions and to allow the follow-up of patients at higher risk for major liver dysfunction. A better understanding of various pathogenic aspects of NASH will help in identifying potential therapeutic approaches in these patients.     

Effects of the Calcium Antagonist Felodipine on Resting and Stress Testing Blood Pressure in Essential Hypertension

The current study analyzed the effects of different doses of the calcium channel blocker felodipine on cardiovascular response to a set of standardized laboratory tasks. We randomly allocated 21 essential hypertensive patients to receive extended release felodipine 5 mg, felodipine 10 mg and placebo, each given once daily for 2 weeks, according to a double-blind 3-period design. At the end of each treatment period, patients were examined at resting baseline and while performing a mental arithmetic test, a handgrip test and a cycle ergometry test. Compared to placebo, the average fall in resting blood pressure (BP) was of 7.9 ± 5.6/6.1 ± 4.5 mm Hg with felodipine 5 mg (p < 0.01) and of 15.1 ± 5.8/13.9 ± 4.5 mm Hg with felodipine 10 mg (p < 0.001). During mental arithmetic, BP decrease was 11.6 ± 8.1/9 ± 5 mm Hg with felodipine 5 mg (p < 0.01) and 20.4 ± 8.1/15.3 ± 5 mm Hg with felodipine 10 mg (p < 0.001). During handgrip test, BP was significantly reduced after both felodipine doses by 11.7 ± 9.3/9.5 ± 6.5 mm Hg (p < 0.05) and 22.1 ± 9.3/22.4 ± 6.5 mm Hg (p < 0.001), respectively. During cycle ergometry, systolic BP was significantly reduced after felodipine 10 mg by 20.1 ± 9.4 mm Hg (p < 0.001), whereas the fall induced by felodipine 5 mg (7.7 ± 9.4 mm Hg) was not statistically significant (p > 0.05); diastolic BP was significantly reduced by both felodipine doses [average fall of 6.6 ± 5.8 mm Hg (p < 0.05) after felodipine 5 mg and of 12.7 ± 5.8 mm Hg (p < 0.001) after felodipine 10 mg]. There was no treatment effect on the magnitude of systolic BP reactivity from baseline during either mental arithmetic, handgrip test or cycle ergometry (all, p > 0.05). Heart rate values were significantly higher after both felodipine doses than after placebo, either at rest or during stress testing (all, p < 0.05). These data suggest that felodipine, especially at higher doses, may be effective in lowering BP not only at rest but also during exposure to commonly recurring stressful situations.     

The anorexia of aging

Malnutrition in the elderly is one of the greatest threats to health, well-being and autonomy, it is therefore crucial to understand and to contrast the causal factors of inadequate energy intake. This review focuses on the mechanisms of the so-called 'anorexia of aging'. In recent years, it has been shown that elderly subjects have abnormal peripheral signal patterns and alterations in central hypothalamic control relays. Negative feedback from impaired gastric motility, exaggerated long-term adiposity signals (leptin, insulin) and postprandial anorexigenic signals (CCK, PYY) seem to prevail over the central feeding drive. If nutritional strategies of intervention are to be improved, these data need to be taken into account.     

Efficacy and safety of abciximab on acute myocardial infarction treated with percutaneous coronary interventions: a meta-analysis of randomized, controlled trials

Objective

To evaluate the efficacy and safety of abciximab following acute myocardial infarction (AMI) treated with percutaneous coronary interventions.

Methods

A meta-analysis of randomized controlled trials of platelet glycoprotein IIb/IIIa inhibitor abciximab as adjunctive therapy to percutaneous coronary interventions for AMI was performed. Main outcomes measured were: (1) mortality, (2) reinfarction, (3) target vessel revascularization (TVR), (4) major cardiac events (MACE) that were a composite endpoint of death, reinfarction, and TVR, and (5) major bleeding.

Results

Six trials randomized 3755 patients who were followed for a mean of 5.5 months. Compared with the control, abciximab significantly reduced mortality (OR 0.70, 95% CI 0.50-0.97), TVR (0.79, 95% CI 0.65-0.96) and MACE (0.76, 95% CI 0.65-0.90). Reduction on TVR and MACE was confirmed in stent patients, but not in balloon angioplasty patients. Abciximab was associated with an increased risk of major bleeding (OR 1.39, 95% CI 1.03-1.87), but bleeding was observed only with a 100U/kg heparin bolus followed by a maintenance infusion (OR 1.89, 95% CI 1.10-3.28) and not with a bolus of 70U/kg (OR 1.22, 95% CI 0.85-1.73).

Conclusions

Abciximab, as adjunctive therapy to percutaneous coronary interventions, reduces mortality, TVR and MACE following AMI. The reduction of clinical outcomes occurs with stent implantation but not with balloon angioplasty. A 70U/kg heparin bolus must be used to avoid major bleeding.