Incremental prognostic value of changes in B-type natriuretic peptide in heart failure

Purpose

B-type natriuretic peptide is one of the most sensitive and specific biohumoral markers of heart failure. We hypothesized that B-type natriuretic peptide changes during treatment of heart failure may provide independent information on disease progression and outcome in patients enrolled in the Val-HeFT trial.

Methods

Patients were divided into four groups according to concentrations of B-type natriuretic peptide at baseline versus 4 months (n = 3740) or 12 months (n = 3343), with respect to the baseline median (97 pg/mL): low→low (stable below median, 44%-46%), high→high (stable above median, 32%-37%), high→low (above to below median, 12%-14%), and low→high (below to above median, 6%-9%). Cox multivariate regression analysis was used to assess the risk of death and morbidity, with adjustment for baseline B-type natriuretic peptide concentrations.

Results

Patients who improved their B-type natriuretic peptide at 4 months (high→low) had a similar risk for mortality (hazard ratio = 1.191, 95% confidence interval [CI] 0.870-1.631, P =.2746) compared with the low→low patients. Conversely, patients who worsened in their B-type natriuretic peptide (low→high) had a risk for mortality (hazard ratio 2.578, CI, 1.861-3.571, P <.0001) higher than patients in the low→low group, and indistinguishable from the high→high group. Worsening of B-type natriuretic peptide (low→high) was associated with 0.03 cm/m² increase in left ventricular end-diastolic diameter, whereas it decreased by 0.10 cm/m² in high→low and low→low groups (P <.001).

Conclusions

Changes in B-type natriuretic peptide over time with respect to a threshold value of 97 pg/mL convey an independent and additional prognostic value compared with a single determination of B-type natriuretic peptide in a large population of patients with chronic symptomatic heart failure and might be helpful in the management of these patients.     

Drawing impairment predicts mortality in severe COPD

BACKGROUND: Cognitive impairment frequently occurs in elderly COPD patients, but little is known about its prognostic implications. We aimed at evaluating the prognostic role of cognitive impairment in patients with severe COPD. METHODS: Our series consisted of 149 stable patients (mean [+/- SD] age, 68.7 +/- 8.5 years) with COPD and a Pao(2) of < 57 mm Hg at rest (n = 97) or at the end of the 6-min walking test (n = 37) who were enrolled in a prospective observational study. After a multidimensional baseline assessment, patients were followed up by telephone calls for a mean duration of 32.5 +/- 9.2 months (minimal follow-up duration, 24 months); 134 patients were successfully tracked. We used multivariable Cox proportional hazard analysis to identify predictors of death among clinical/functional variables that previously were shown to have prognostic implications and among neuropsychological indexes selected on the basis of univariate analysis. RESULTS: We observed 29 deaths over a median follow-up time of 32 months. Only the two following variables were independently associated with the outcome: an abnormal score on the copy with landmark test (hazard ratio [HR], 2.93; 95% confidence interval [CI], 1.34 to 6.39); and a 6-min walk distance of < 300 m (HR, 3.46; 95% CI, 1.15 to 10.5). A Pao(2) of < 57 mm Hg at rest (HR, 2.19; 95% CI, 0.93 to 5.18) and an FEV(1) of < 40% predicted (HR, 2.74; 95% CI, 0.99 to 7.57) were nearly significantly associated with the outcome, while Paco(2), body mass index, physical dependence, comorbid diseases, and the impairment of cognitive domains other than drawing impairment were unrelated to the outcome. CONCLUSIONS: Drawing impairment is a risk factor for mortality and might improve the assessment of hypoxemic COPD patients.     

Beta-lipoprotein- and LDL-associated serum gamma-glutamyltransferase in patients with coronary atherosclerosis

Elevation of serum gamma-glutamyltransferase (GGT) activity is a risk factor for myocardial infarction and stroke. GGT activity can catalyze the oxidation of low-density lipoprotein (LDL), a process involved in the pathogenesis of atherosclerosis. Serum GGT is partially adsorbed onto circulating LDL, and catalytically active GGT has been found within atherosclerotic plaques, colocalizing with oxidized LDL and foam cells. We investigated the the nature of the LDL-associated GGT, the degree of correlation between total serum GGT levels and beta-lipoprotein (beta-LP)-associated GGT, and whether this association is altered in subjects with coronary artery disease (CAD). LDL-bound GGT showed an entire, amphiphilic heavy chain, but the association was easily lost during LDL purification by affinity chromatography. When the activity of GGT associated with polycation-precipitated beta-lipoproteins was assayed, an identical immunoreactive GGT was found in Western blot, and a statistically significant linear correlation was found between total serum GGT levels and the corresponding beta-LP-bound activities (p<0.0001) in controls and patients with CAD. Nevertheless, subjects with CAD presented a lower ratio of beta-LP-bound GGT to total serum GGT respect to controls (p<0.05) and healthy subjects with elevated serum GGT (p<0.01). In addition, a relative decrease of total serum GGT was observed in CAD subjects of older age as compared to younger ones (p<0.005).     

Current views of the risk of stroke for migraine with and migraine without aura

The association between migraine and stroke is complex and is a continued focus of attention. Several observational studies have identified migraine as an independent risk factor for ischemic stroke. However, a distinction should be made between migraine with and migraine without aura. The migraine-stroke association is mostly apparent for young women with migraine with aura. The association between migraine with aura and stroke is weaker in older age groups, which may be due to the fact that traditional cardiovascular risk factors are more prominent with increasing age. Most studies have not found an association between migraine without aura and ischemic stroke. Although there are several hypotheses about the biologic link between migraine with aura and ischemic stroke, the precise mechanisms remain unclear. However, because the absolute risk of stroke is low in patients with migraine with aura, and migraine without aura is likely not associated with ischemic stroke, most migraine patients will not experience a stroke event.     

Sporadic ALS is not associated with VAPB gene mutations in Southern Italy

There is evidence that multiple sclerosis (MS) may associated with cognitive impairment in 25 to 40% of cases. The gene encoding myeloperoxidase (MPO) is involved in molecular pathways leading to β-amyloid deposition. We investigated a functional biallelic (G/A) polymorphism in the promoter region (-463) of the MPO gene in 465 patients affected by MS, divided into 204 cognitively normal and 261 impaired. We did not find significant differences in allele or genotype distributions between impaired and preserved MS patients. Our findings suggest that MPO polymorphism is not a risk factor for cognitive impairment in MS.     

Teachers' perception of oral health status. Design and validation of an evaluation instrument

The evaluation of health status is a complex process that requires the use of indicators that assess health both in terms of disease and of the impact the health-disease-care process has on the quality of life. The aim of the present study was to design and validate an instrument to evaluate teachers 'perceptions of oral health status. The sample comprised 78 teachers of 4 schools (province of Buenos Aires). DESIGN OF THE INSTRUMENT: (a) identification of the 5 categories that compose the instrument and can measure the object of study based on evidence; (b) creation of a questionnaire that contains 32 items by two researchers; (c) evaluation of the questionnaire by 5 professionals of 4 different professions to standardize criteria (Ventegodt et al, 2003) applying an ordinal scale. Items were reduced to 25 (Index of perception of oral health: IPOH). VALIDATION OF THE INSTRUMENT: the following parameters were evaluated: reliability employing the test-retest method at 30 days; internal consistency employing Cronbach's a coefficient (1951); content validity determined by two experts; construct validity employing the method of extreme groups (Student's t test). The established categories were knowledge on oral health, personal experience with oral health care, expectations regarding their students 'families, expectations regarding dentistry, satisfaction with his/her role as a teacher The instrument proved to be reliable as evidenced by a value of r = 0.80 in the test-retest method; a satisfactory intra-items consistency was evidenced by Cronbach's alpha coefficient value of 0.82. The differences between the results of the groups of teachers in the extreme groups were statistically significant (p = 2.2). The instrument designed to measure the teachers' perception of oral health status would be valid. It would be desirable to enlarge the sample and determine criterion validity by comparison with other instruments.     

Activating PTPN11 mutations play a minor role in pediatric and adult solid tumors

The PTPN11 gene encodes SHP-2, a widely expressed cytoplasmic protein tyrosine phosphatase functioning as a signaling transducer. Germ-line PTPN11 mutations cause Noonan syndrome (NS), a developmental disorder characterized by an increased risk of malignancies. Recently, a novel class of activating mutations in PTPN11 has been documented as a somatic event in a heterogeneous group of leukemias. Because of the relatively higher prevalence of certain solid tumors in children with NS and the positive modulatory function of SHP-2 in RAS signaling, a wider role for activating PTPN11 mutations in cancer has been hypothesized. Here, we screened a number of solid tumors, including those documented in NS or in which deregulated RAS signaling occurs at significant frequency, for PTPN11 mutations. No disease-associated mutation was identified in rhabdomyosarcoma (n = 13), neuroblastoma (n = 32), melanoma (n = 50), thyroid (n = 85), and colon (n = 48) tumors; a novel missense change, promoting an increased basal phosphatase activity of SHP-2, was observed in one glioma specimen. Our data document that deregulated SHP-2 function does not represent a major molecular event in pediatric and adult tumors, further supporting our previous evidence indicating that the oncogenic role of PTPN11 mutations is cell-context specific.     

Incidence and time course of Leishmania infantum infections examined by parasitological, serologic, and nested-PCR techniques in a cohort of naive dogs exposed to three consecutive transmission seasons

Most experience in the comparison of diagnostic tools for canine leishmaniasis comes from cross-sectional surveys of dogs of different ages and breeds and in cases with unknown onset and duration of leishmaniasis. A longitudinal study was performed on 43 beagle dogs exposed to three transmission seasons (2002 to 2004) of Mediterranean leishmaniasis and examined periodically over 32 months through bone marrow microscopy and nested PCR (n-PCR), lymph node culture, serology (immunofluorescent-antibody test), and evaluation of clinical parameters. Starting from January 2003, the highest rate of positives was detected by n-PCR at all assessments (from 23.3% to 97.3%). Sensitivities of serologic and parasitological techniques were lower but increased with time, from 15.8% to 75.0 to 77.8%. Some dogs that tested positive by n-PCR but negative by other tests ("subpatent infection") remained so until the end of the study or converted to negative in subsequent assessments, whereas all dogs with positive serology and/or microscopy/culture ("asymptomatic patent infection") exhibited progressive leishmaniasis; 68% of them developed clinical disease ("symptomatic patent infection") during the study, at 7 (range, 3 to 14) months after being positive to all tests. Postexposure infection incidences were high and were significantly different between 2002 and 2003 exposures (39.5% and 91.7%, respectively). The time course of infection was highly variable in each dog, with three patterns being identified: (i) rapid establishment of a patent condition (0 to 2 months from detection of infection); (ii) a prolonged subpatent condition (4 to 22 months) before progression; and (iii) a transient subpatent condition followed by 10 to 21 months of apparent Leishmania-negative status before progression.