Vascular endothelial growth factor, left ventricular dysfunction and mortality in hemodialysis patients

OBJECTIVES: Vascular endothelial growth factor induces nitric oxide-dependent angiogenic effects and participates in the inflammatory response. This cytokine is over-expressed in the myocardium in experimental models of pressure overload and renal mass ablation, and vascular endothelial growth factor is increased in end-stage renal disease. We investigated the relationship between vascular endothelial growth factor, left ventricular function (by midwall fractional shortening) and mortality in a prospective cohort study in 228 hemodialysis patients. RESULTS: Serum vascular endothelial growth factor concentration was associated directly with interleukin-6 and tumor necrosis factor-alpha (P < 0.01) and inversely with albumin (P = 0.007) but was independent of the endogenous inhibitor of nitric oxide synthesis, asymmetric dimethylarginine. Vascular endothelial growth factor was inversely related with midwall fractional shortening (P = 0.002) and predicted mortality (P = 0.02). In multivariate analyses testing the involvement of this angiogenic cytokine in left ventricular dysfunction and death, these links remained substantially unmodified after adjustment for Framingham risk factors, risk factors peculiar to end-stage renal disease (Hb, Ca, P) and previous cardiovascular complications. However, these links became weaker and not significant when biomarkers of inflammation and asymmetric dimethylarginine were sequentially introduced into the multivariate models. In crude and adjusted analyses, left ventricular function was lowest in patients who displayed both high vascular endothelial growth factor and high asymmetric dimethylarginine, intermediate in patients with either high vascular endothelial growth factor or high asymmetric dimethylarginine and highest in those with low asymmetric dimethylarginine and low vascular endothelial growth factor (P = 0.001). CONCLUSION: Vascular endothelial growth factor is associated with left ventricular systolic dysfunction and mortality in hemodialysis patients. Vascular endothelial growth factor appears to be in the pathway whereby inflammation and nitric oxide inhibition lead to cardiomyopathy and death in hemodialysis patients.     

Progressive decrease of hepatitis B in a cohort of drug users followed over a period of 15 years: the impact of anti-HBV vaccination

In the Western world, the population at the highest risk of HBV infection is probably that of illicit drug users (DUs). Since 1985, 1 Public Health Centre for Drug Users (PHCDU), in north-eastern Italy, has been asking all heroin DUs, whether in treatment or not, to undergo screening for HIV, HBV and, since 1989, for HCV infection. Since 1988 the Centre has proposed HBV vaccination to all patients who were negative for all HBV markers. From 1985 to 2001 895 heroin DUs were screened, 726 males and 169 females. 442 (49.4%) were negative to HBV markers at the first control and 72.4% received at least 1 dose of the vaccine. 320 DUs were vaccinated and a total of 995 doses of recombinant vaccine were administered. The anti-HBc antibody appeared in 2 vaccinated patients out of 258 DUs undergoing controls, while 13 seroconversions for anti-HBc occurred in 45 DUs who had refused to be vaccinated. On the basis of these results, HBV vaccination of DUs can be strongly recommended. Vaccination showed a good adherence in a population difficult to treat and can have a leading role in reducing HBV infection in DUs and their contacts.     

Acute pancreatitis in elderly patients: a single-center retrospective evaluation of clinical outcomes

Introduction: Acute pancreatitis (AP) incidence in the elderly population has increased in the last years. However, the role of age as influencing factor on the AP clinical course is still debated.

Methods: We reviewed clinical records of consecutive patients admitted with diagnosis of AP. Patients were divided in elderly (≥65 years) and non-elderly (<65 years). Primary endpoint was comparison of overall mortality. Secondary endpoint included ICU admission, in-hospital length of stay (LOS) and surgical procedures.

Results: We enrolled 352 elderly and 532 non-elderly patients. A higher mortality rate (7.4% vs 1.9%; p?<?.001), ICU admission rate (18.9% vs 6.3%; p?<?.001) and prolonged length of hospital stay (9 (6–14) vs 7 (5–11.7) days; p?=?.01) were registered in the ≥65 years group. Multivariate analysis identified age (OR: 3.5; 95% CI:1.645–7.555; p?=?.001), a higher Ranson score at admission (OR: 5.52; 95% CI:1.11–27.41; p<.001) and necrotic pancreatitis (OR: 8.6; 95% CI:2.46–30.27; p?=?.001) as independent predictors of mortality. Conversely age and necrotic pancreatitis were independent risk factors for higher LOS and ICU admission.

Conclusions: Patients with AP and age ≥65 years have a higher mortality, ICU admission and prolonged LOS. Early recognition and prompt treatment are key elements to improve outcomes in this population.     

Hb Belfast [beta15(A12)Trp-->Arg]: definition of the clinical and hematological phenotype

We report the sixth occurrence of Hb Belfast [beta15(A12)Trp-->Arg], a mild, unstable beta chain variant, in a large family wherein nine subjects were affected. DNA analysis showed a TUG-->AGG mutation at codon 15 of the beta-globin gene, confirming a Trp-->Arg amino acid substitution. The oxygen affinity of the isolated variant was increased. The clinical phenotype is silent or very mild, the only clinical finding being an intermittent moderate jaundice.     

Neuroendocrine response to the serotonin agonist M-chlorophenylpiperazine in women with menstrual status migrainosus

To assess the neuroendocrine correlates of menstrual status migrainosus (MSM) and menstrual migraine (MM), we evaluated the prolactin (PRL) and cortisol responses to the direct central serotoninergic (5-HT) agonist meta-chlorophenylpiperazine (m-CPP) administered orally (0.5 mg/kg) during the follicular (FP: +6, +8) and luteal phases (LP: -4, -6) of the same menstrual cycle. Ten women with MSM (migraine attacks occurring within 2 days of the onset of menstrual bleeding but lasting more than 72 h) and 9 women with MM (migraine occurring within 2 days of the onset of menstrual bleeding with a typical duration of attacks) were studied. Six healthy women served as controls. Blood samples were taken at times -30, 0 and every 30 min over 4 h. Statistical analysis was performed using MANOVA followed by Duncan's post hoc comparisons. We found that the PRL response to the m-CPP test was significantly blunted in MSM compared with MM and controls in both phases of the menstrual cycle (F = 4.6; p < 0.001). Indeed, the PRL area under the curve (AUC) after m-CPP was higher in both MM and controls compared with MSM (F = 12.7; p < 0.001). The m-CPP-induced cortisol response was absent in MSM compared with MM and controls in both FP and LP (F = 4.1; p < 0.001). On the other hand, the pattern of the plasma cortisol response to m-CPP was similar in MM and controls throughout the menstrual cycle. In addition, the basal plasma cortisol levels were significantly higher in MSM compared with controls (p < 0.001) and MM (p < 0.001) during FP, but not in LP, and progressively decreased over time. Thus, no significant effect of the menstrual cycle phase and diagnosis on the cortisol AUC was found, while a significant diagnosis effect (F = 25.6; p < 0.001) on %delta(max) plasma cortisol levels was evident and consistent with the lack of cortisol response to m-CPP in MSM during the FP and LP compared with MM and controls. A derangement in central 5-HT control of pituitary PRL, and even more so in cortisol release, is present in women with MSM, but not with MM, regardless of the phase of the menstrual cycle, suggesting the involvement of some 5-HT(1) and 5-HT(2) receptor subtypes in the occurrence of extremely severe migraine attacks triggered by menstruation.     

Recombinant human erythropoietin in very elderly patients with myelodysplastic syndromes: results from a retrospective study

Myelodysplastic syndromes (MDS) are common in elderly patients. Recombinant human erythro-poietin (rHuEPO) has been widely used to treat anemia in lower risk MDS patients, but few data are known about rHuEPO treatment in the very elderly patient group. In order to investigate the role of rHuEPO treatment in terms of response, overall survival (OS), and toxicity in a very elderly MDS patient group, 93 MDS patients treated with rHuEPO when aged ≥80 years were selected among MDS cases enrolled in a retrospective multicenter study by the cooperative group Gruppo Romano Mielodisplasie (GROM) from Jan 2002 to Dec 2010. At baseline, median age was 82.7 (range 80–99.1) with a median hemoglobin (Hb) level of 9 g/dl (range 6–10.8). The initial dose of rHuEPO was standard (epoetin alpha 40,000 IU/week or epoetin beta 30,000 IU/week) in 59 (63.4 %) pa-tients or high in 34 (36.6 %) (epoetin alpha 80,000 IU/week) patients. We observed an erythroid response (ER) in 59 (63.4 %) patients. No thrombotic event was reported. Independent predictive factors for ER were low transfusion requirement before treatment (p?=?0.004), ferritin <200 ng/ml (p?=?0.017), Hb >8 g/dl (p?=?0.034), and a high-dose rHuEPO treatment (p?=?0.032). Median OS from rHuEPO start was 49.3 months (95 % CI 27.5–68.4) in responders versus 30.6 months (95 % CI 7.3–53.8) in resistant patients (p?=?0.185). In conclusion, rHuEPO treatment is safe and effective also in the very elderly MDS patients. However, further larger studies are warranted to evaluate if EPO treatment could be worthwhile in terms of quality of life and cost-efficacy in very old patients.     

Impact of multivessel disease on infarct size among STEMI patients undergoing primary angioplasty

Background

Although primary angioplasty achieves Thrombolysis In Myocardial Infarction (TIMI) 3 flow in most patients with ST-elevation myocardial infarction, epicardial recanalization does not guarantee optimal perfusion in a large proportion of patients. Multivessel disease has been demonstrated to be associated with impaired survival, however its impact on infarct size has not been largely investigated, that therefore is the aim of the current study.

Methods

Our population is represented by 827 STEMI patients undergoing primary PCI. Infarct size was evaluated at 30 days by technetium-99m-sestamibi.

Results

Multivessel disease was observed in 343 patients (41.5%). It was associated with older age (65 [57–74] vs 63 [53–71], p < 0.001), higher rate of previous MI (6.4% vs 2.5%, p = 0.005), longer ischemia time evaluated as continuous variable (210 [155–280] min vs 196 [145–270] min, p = 0.065) or percentage of patients with ischemia time >3 h (63.7% vs 56.4%, p = 0.038), and a trend in more cardiogenic shock (5.5% vs 2.9%, p = 0.055). Patients with multivessel disease received more often Abciximab (92.1% vs 88.4%, p < 0.001), Intra-aortic balloon pump (6.4% vs 1.9%, p < 0.001). No differences were observed in other clinical or angiographic characteristics. In particular, multivessel disease did not affect the rate of postprocedural TIMI 3 flow (90.9% vs 93.4%, p = 0.18) and ST-segment resolution (52.4% vs 54.9%, p = 0.48). Multivessel disease did not affect infarct size (12.7% [4.5%–24.9%] vs 12.3% [4%–24.1%], p = 0.58). Similar results were observed in subanalyses without any significant interaction for each variable (anterior infarct location (p int = 0.23), gender (p int = 0.9), age (p int = 0.7), diabetes (p int = 0.15)). The absence of any impact of multivessel disease on infarct size was confirmed when the analysis was conducted according to the percentage of patients with infarct size above the median, even after correction for baseline characteristics, such as age, previous MI, ischemia time, use of Gp IIb–IIIa inhibitors, cardiogenic shock, ischemia time (OR [95% CI] = 1.09 [0.82–1.45], p = 0.58).

Conclusions

This study shows that among STEMI patients undergoing primary PCI multivessel disease does not affect infarct size.     

Satisfaction,quality of life and therapy adherence assessment in real life patients transitioning from vitamin K antagonists to direct oral anticoagulants

Journal of Thrombosis and Thrombolysis - Anticoagulant therapy has undergone a significant change since direct oral anticoagulants (DOACs) introduction. Their obvious advantages including the fixed...     

Brain networks disconnection in early multiple sclerosis cognitive deficits: An anatomofunctional study

Severe cognitive impairment involving multiple cognitive domains can occur early during the course of multiple sclerosis (MS). We investigated resting state functional connectivity changes in large‐scale brain networks and related structural damage underlying cognitive dysfunction in patients with early MS. Patients with relapsing MS (3–5 years disease duration) were prospectively assigned to two groups based on a standardized neuropsychological evaluation: (1) cognitively impaired group (CI group, n = 15), with abnormal performances in at least 3 tests; (2) cognitively preserved group (CP group, n = 20) with normal performances in all tests. Patients and age‐matched healthy controls underwent a multimodal 3T magnetic resonance imaging (MRI) including anatomical T1 and T2 images, diffusion imaging and resting state functional MRI. Structural MRI analysis revealed that CI patients had a higher white matter lesion load compared to CP and a more severe atrophy in gray matter regions highly connected to networks involved in cognition. Functional connectivity measured by integration was increased in CP patients versus controls in attentional networks (ATT), while integration was decreased in CI patients compared to CP both in the default mode network (DMN) and ATT. An anatomofunctional study within the DMN revealed that functional connectivity was mostly altered between the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) in CI patients compared to CP and controls. In a multilinear regression model, functional correlation between MPFC and PCC was best predicted by PCC atrophy. Disconnection in the DMN and ATT networks may deprive the brain of compensatory mechanisms required to face widespread structural damage. Hum Brain Mapp 35:4706–4717, 2014. © 2014 Wiley Periodicals, Inc .