A Propensity Score Analysis Shows that Empirical Treatment with Linezolid Does Not Increase the Thirty-Day Mortality Rate in Patients with Gram-Negative Bacteremia

The role of linezolid in empirical therapy of suspected bacteremia remains unclear. The aim of this study was to evaluate the influence of empirical use of linezolid or glycopeptides in addition to other antibiotics on the 30-day mortality rates in patients with Gram-negative bacteremia. For this purpose, 1,126 patients with Gram-negative bacteremia in the Hospital Clinic of Barcelona from 2000 to 2012 were included in this study. In order to compare the mortality rates between patients who received linezolid or glycopeptides, the propensity scores on baseline variables were used to balance the treatment groups, and both propensity score matching and propensity-adjusted logistic regression were used to compare the 30-day mortality rates between the groups. The overall 30-day mortality rate was 16.0% during the study period. Sixty-eight patients received empirical treatment with linezolid, and 1,058 received glycopeptides. The propensity score matching included 64 patients in each treatment group. After matching, the mortality rates were 14.1% (9/64) in patients who received glycopeptides and 21.9% (14/64) in those who received linezolid, and a nonsignificant association between empirical linezolid treatment and mortality rate (odds ratio [OR], 1.63; 95% confidence interval [CI], 0.69 to 3.82; P = 0.275, McNemar''s test) was found. This association remained nonsignificant when variables that remained unbalanced after matching were included in a conditional logistic regression model. Further, the stratified propensity score analysis did not show any significant relationship between empirical linezolid treatment and the mortality rate after adjustment by propensity score quintiles or other variables potentially associated with mortality. In conclusion, the propensity score analysis showed that empirical treatment with linezolid compared with that with glycopeptides was not associated with 30-day mortality rates in patients with Gram-negative bacteremia.     

C(-106)T polymorphism of the aldose reductase gene and the progression rate of diabetic retinopathy

PURPOSE: To study the C(-106)T polymorphism in the promoter of the aldose reductase (ALR2) gene: (a) its local prevalence and (b) its modulation of the susceptibility for developing retinopathy. METHODS: DNAs of 96 control subjects and 53 long-standing (duration 17.9+/-5.4 years) type-2 diabetic patients were analyzed by PCR-RFLP with BfaI enzyme. Retinopathy was graded with 2-eye, 7-field fundus color photography. The IMF-HbA1c was the arithmetic mean of all HbA1c's of each patient. RESULTS: The genotypes in the controls were CC=57 (59.4%), CT=32 (33.3%) and TT=7 (7.3%), with Hardy-Weinberg chi(2)=0.793 (p>0.50). Among 53 diabetics, CC=24 (45.3%), CT=26 (49.0%) and TT=3 (5.7%). The correlation between IMF-HbA1c and retinopathy progression rate was significant on CC (r=0.6102, p=0.0072) but not in CT+TT genotypes (r=0.26, p=0.1811). CONCLUSIONS: In Chilean adults, the frequency of the C(-106)T polymorphism of the ALR2 gene was similar to that reported by others. Type-2 diabetics with the CC genotype were more susceptible for developing retinopathy as a result of chronic hyperglycemia than those with the CT or TT genotype.     

Simultaneous determination of new-generation antidepressants in plasma by gas chromatography–mass spectrometry

We have developed a gas chromatography–mass spectrometry (GC–MS) method for plasma for the determination of new-generation antidepressants, including olanzapine (antipsychotic used in bipolar disorder), and antidepressant selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine and its metabolite norfluoxetine, paroxetine, sertraline, venlafaxine, and mirtazapine. Sample preparation was performed by liquid–liquid extraction with tert-butyl methyl ether. Fluoxetine, norfluoxetine, sertraline, and paroxetine required subsequent derivatization with 1-(heptafluorobutyryl) imidazole (HFBI). The GC separation lasts a total of 23.76 min. Qualitative and quantitative analysis were performed using an electron-impact ionization gas chromatograph interfaced to a mass-selective detector in selected-ion monitoring mode to increase the sensitivity of the method. Method validation was performed taking into account linearity, sensitivity, selectivity, accuracy, precision, and recovery, achieving good results for all the parameters studied. Calibration curves were prepared in the range of 0.005–2 μg/ml (according to the therapeutic and toxic concentrations of each individual compound), with all correlation coefficients R ² > 0.99. The limit of quantification was between 0.005 and 0.1 μg/ml, depending on the compound, whereas the limit of detection ranged from 0.0025 to 0.05 μg/ml. The method is fast and simple, allowing the identification and quantification of some of the most widely used antidepressants at therapeutic or toxic concentrations, and may be useful in routine clinical and forensic toxicology analysis.     

Surgical treatment of localized gingival recessions using coronally advanced flaps with or without subepithelial connective tissue graft

Background

A coronally advanced flap with subepithelial connective tissue graft is the gold standard surgical treatment of gingival recessions, since it offers a higher probability of achieving complete root coverage compared with other techniques. However, optimum short- and middle-term clinical results have also been obtained with coronally advanced flaps alone. The aim of the present study was to evaluate the results obtained by the surgical treatment of localized gingival recessions using coronally advanced flaps with or without subepithelial connective tissue graft.

Material and Methods

The reduction of recession height was assessed, together with the gain in gingival attachment apical to the recession, and total reduction of recession, in a comparative study of two techniques. Twenty-two gingival recessions were operated upon: 13 in the control group (coronally advanced flap) and 9 in the test group (coronally advanced flap associated to subepithelial connective tissue graft).

Results

After 18 months, the mean reduction of recession height was 2.2 ± 0.8 mm in the control group and 2.3 ± 0.7 mm in the test group, with a mean gain in gingival attachment of 1.3 ± 0.9 mm and 2.3 ± 1.3 mm, respectively. In percentage terms, the mean reduction of recession height was 84.6 ± 19.6% in the control group and 81.7 ± 17.8% in the test group, with a mean gain in gingival attachment of 20.5 ± 37.4% and 184.4 ± 135.5%, respectively.

Conclusions

Significant reduction of gingival recession was achieved with both techniques, though the mean gain in gingival attachment (in mm and as a %) was greater in test group. Key words:Gingival recession, coronally advanced flap, subepthelial connective tissue graft.     

Co-culture of hematopoietic stem cells with mesenchymal stem cells increases VCAM-1-dependent migration of primitive hematopoietic stem cells

Hematopoietic stem cells (HSC) lose their capacity for engraftment during ex vivo cytokine expansion. It has been shown that mesenchymal stem cells (MSC) improve HSC transplantability; however, the molecular mechanisms responsible for this effect have not yet been completely elucidated. This paper reports that expanding HSC in co-culture with MSC enhances a vascular cell adhesion molecule (VCAM-1)-dependent pro-migratory phenotype. MSC did not regulate the HSC expression of CD49d (VCAM-1 counter-receptor molecule), but did decrease the cytokine-induced HSC VCAM-1-mediated pro-adhesive phenotype. Co-culture with MSC reduced the expression of the inactive conformation of lymphocyte function-associated antigen (LFA-1) at the HSC uropod, and induced higher expression of an LFA-1 activation epitope. Interestingly, VCAM-1-dependent HSC migration was modulated by targeting this LFA-1 high affinity form, suggesting integrin cross-regulation. VCAM-1-mediated HSC transmigration appeared to favor the more primitive HSC immunophenotype. Our results suggested that co-culture with MSC improved VCAM-1-dependent migration of primitive HSC, which was affected in ex vivo cytokine-expanded HSCs by a mechanism involving LFA-1 modulation.     

Changes in plasma and platelet BDNF levels induced by <Emphasis Type="Italic">S</Emphasis>-citalopram in major depression

Background  

Neuroplastic processes are thought to be involved in the pathophysiology of major depression. It has been reported that serum brain-derived neurotrophic factor (BDNF) is decreased in depressed patients.     

Additive effects of <Emphasis Type="Italic">LPL</Emphasis>, <Emphasis Type="Italic">APOA5</Emphasis> and <Emphasis Type="Italic">APOE</Emphasis>variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study

Background  

Hypertriglyceridemia (HTG) is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG) metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information.     

Increased local procoagulant action: a mechanism contributing to the favorable hemostatic effect of recombinant FVIIa in PLT disorders

BACKGROUND: Recombinant FVIIa (rFVIIa) has been shown to improve hemostasis in patients with thrombocytopenia and to prevent or control bleeding episodes in patients with inherited deficiencies of major PLT glycoproteins, but the mechanism of action is not well understood. STUDY DESIGN AND METHODS: Effects of rFVIIa on hemostasis were explored with an in vitro perfusion technique. Blood samples, from healthy donors or from patients with congenital defects of PLT glycoprotein IIb-IIIa (GPIIb-IIIa), were anticoagulated with low-molecular-weight heparin. Experimental thrombocytopenia (<6000 PLTs/microL) was induced by a filtration procedure. rFVIIa was added to blood samples at therapeutic concentrations. A severe GPIIb-IIIa impairment was also induced by exposure of normal blood samples to a specific antibody. Perfusion studies were performed through annular chambers containing damaged vascular segments. The presence of fibrin and PLTs on the perfused subendothelium was morphometrically quantified. RESULTS: Under conditions of experimental thrombocytopenia, addition of rFVIIa enhanced fibrin formation in a dose-dependent manner (p < 0.05). Improvements in local fibrin generation and partial restoration of PLT interactions were also observed after incubation of blood from patients with Glanzmann's thrombasthenia with rFVIIa at 5 microg per mL (180 microg/kg). Similar improvements were observed in blood samples incubated with antibodies to GPIIb-IIIa. rFVIIa in whole normal blood also enhanced fibrin formation but PLT deposition was unaffected. Evaluation of prothrombin fragments 1 and 2 in the perfusates confirmed that rFVIIa increased thrombin generation in all cases. CONCLUSION: Our data indicate that rFVIIa promotes a procoagulant activity at sites of vascular damage. This mechanism could explain the beneficial hemostatic effect of rFVIIa in patients with thrombocytopenia or with Glanzmann's thrombasthenia.     

Congenital partial absence of the pericardium in a young man with atypical chest pain

Pericardial defects are infrequent congenital anomalies due to agenesis caused by premature atrophy of the common cardinal vein or Cuvier duct during the 5^th or 6^th week of embryonic life. These congenital defects are rare, typically observed as an incidental finding and usually remain asymptomatic. Nevertheless, the more widespread use of modern imaging techniques has contributed to an increase of its incidence in recent years. There is currently no consensus regarding therapeutic options, all of which are based on small retrospective studies that evaluate the risk of developing a life-threatening complication such as herniation and incarceration of the myocardium. We report on a 22-year-old male who presented with sudden onset of sharp chest pain and dyspnea. Computed tomography and cardiac magnetic resonance scan revealed a pericardial defect adjacent to the lateral free wall of the left atrium with associated herniation of the left atrial appendage. The patient was managed conservatively and had an uneventful clinical progress.