Topical use of tranexamic acid in coronary artery bypass operations: A double-blind, prospective, randomized, placebo-controlled study

AbstractObjectives: We sought to investigate the effect of topical application of tranexamic acid into the pericardial cavity in reducing postoperative blood loss in coronary artery surgery. Methods: A prospective, randomized, double-blind investigation with parallel groups was performed. Forty consecutive patients undergoing primary coronary surgery were randomly assigned to group 1 (tranexamic acid group) or group 2 (placebo group). Tranexamic acid (1 g in 100 mL of saline solution) or placebo was poured into the pericardial cavity and over the mediastinal tissues before sternal closure. The drainage of mediastinal blood was measured hourly. Results: Chest tube drainage in the first 24 hours was 485 ± 166 mL in the tranexamic acid group and 641 ± 184 mL in the placebo group (P = .01). Total postoperative blood loss was 573 ± 164 mL and 739 ± 228 mL, respectively (P = .01). The use of banked donor blood products was not significantly different between the two groups. Tranexamic acid could not be detected in any of the blood samples blindly collected from 24 patients to verify whether any systemic absorption of the drug occurred. There were no deaths in either group. None of the patients required reoperation for bleeding. Conclusions: Topical application of tranexamic acid into the pericardial cavity after cardiopulmonary bypass in patients undergoing primary coronary bypass operations significantly reduces postoperative bleeding. Further studies must be carried out to clarify whether a more pronounced effect on both bleeding and blood products requirement might be seen in procedures with a higher risk of bleeding. (J Thorac Cardiovasc Surg 2000;119:575-80

Should severe monolateral asymptomatic carotid artery stenosis be treated at the time of coronary artery bypass operation?

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Neurophysiological and BOLD signal uncoupling of giant somatosensory evoked potentials in progressive myoclonic epilepsy: a case-series study

In progressive myoclonic epilepsy (PME), a rare epileptic syndrome caused by a variety of genetic disorders, the combination of peripheral stimulation and functional magnetic resonance imaging (fMRI) can shed light on the mechanisms underlying cortical dysfunction. The aim of the study is to investigate sensorimotor network modifications in PME by assessing the relationship between neurophysiological findings and blood oxygen level dependent (BOLD) activation. Somatosensory-evoked potential (SSEP) obtained briefly before fMRI and BOLD activation during median-nerve electrical stimulation were recorded in four subjects with typical PME phenotype and compared with normative data. Giant scalp SSEPs with enlarger N20-P25 complex compared to normal data (mean amplitude of 26.2\u2009\ub1\u20098.2\u2009\u3bcV after right stimulation and 27.9\u2009\ub1\u20093.7\u2009\u3bcV after left stimulation) were detected. Statistical group analysis showed a reduced BOLD activation in response to median nerve stimulation in PMEs compared to controls over the sensorimotor (SM) areas and an increased response over subcortical regions (p\u2009\u20092.3, corrected). PMEs show dissociation between neurophysiological and BOLD findings of SSEPs (giant SSEP with reduced BOLD activation over SM). A direct pathway connecting a highly restricted area of the somatosensory cortex with the thalamus can be hypothesized to support the higher excitability of these areas

Inefficient white matter activity in Schizophrenia evoked during intra and inter-hemispheric communication

Intensive cognitive tasks induce inefficient regional and network responses in schizophrenia (SCZ). fMRI-based studies have naturally focused on gray matter, but appropriately titrated visuo-motor integration tasks reliably activate inter- and intra-hemispheric white matter pathways. Such tasks can assess network inefficiency without demanding intensive cognitive effort. Here, we provide the first application of this framework to the study of white matter functional responses in SCZ. Event-related fMRI data were acquired from 28 patients (nine females, mean age 43.3, ±11.7) and 28 age- and gender-comparable controls (nine females, mean age 42.1 ± 10.1), using the Poffenberger paradigm, a rapid visual detection task used to induce intra- (ipsi-lateral visual and motor cortex) or inter-hemispheric (contra-lateral visual and motor cortex) transfer. fMRI data were pre- and post-processed to reliably isolate activations in white matter, using probabilistic tractography-based white matter tracts. For intra- and inter-hemispheric transfer conditions, SCZ evinced hyper-activations in longitudinal and transverse white matter tracts, with hyper-activation in sub-regions of the corpus callosum primarily observed during inter-hemispheric transfer. Evidence for the functional inefficiency of white matter was observed in conjunction with small (~50 ms) but significant increases in response times. Functional inefficiencies in SCZ are (1) observable in white matter, with the degree of inefficiency contextually related to task-conditions, and (2) are evoked by simple detection tasks without intense cognitive processing. These cumulative results while expanding our understanding of this dys-connection syndrome, also extend the search of biomarkers beyond the traditional realm of fMRI studies of gray matter

Activations in gray and white matter are modulated by uni-manual responses during within and inter-hemispheric transfer: effects of response hand and right-handedness

Because the visual cortices are contra-laterally organized, inter-hemispheric transfer tasks have been used to behaviorally probe how information briefly presented to one hemisphere of the visual cortex is integrated with responses resulting from the ipsi- or contra-lateral motor cortex. By forcing rapid information exchange across diverse regions, these tasks robustly activate not only gray matter regions, but also white matter tracts. It is likely that the response hand itself (dominant or non-dominant) modulates gray and white matter activations during within and inter-hemispheric transfer. Yet the role of uni-manual responses and/or right hand dominance in modulating brain activations during such basic tasks is unclear. Here we investigated how uni-manual responses with either hand modulated activations during a basic visuo-motor task (the established Poffenberger paradigm) alternating between inter- and within-hemispheric transfer conditions. In a large sample of strongly right-handed adults (n = 49), we used a factorial combination of transfer condition [Inter vs. Within] and response hand [Dominant(Right) vs. Non-Dominant (Left)] to discover fMRI-based activations in gray matter, and in narrowly defined white matter tracts. These tracts were identified using a priori probabilistic white matter atlases. Uni-manual responses with the right hand strongly modulated activations in gray matter, and notably in white matter. Furthermore, when responding with the left hand, activations during inter-hemispheric transfer were strongly predicted by the degree of right-hand dominance, with increased right-handedness predicting decreased fMRI activation. Finally, increasing age within the middle-aged sample was associated with a decrease in activations. These results provide novel evidence of complex relationships between uni-manual responses in right-handed subjects, and activations during within- and inter-hemispheric transfer suggest that the organization of the motor system exerts sophisticated functional effects. Moreover, our evidence of activation in white matter tracts is consistent with prior studies, confirming fMRI-detectable white matter activations which are systematically modulated by experimental condition

Upregulation of MAPK pathway is associated with survival in castrate-resistant prostate cancer

BACKGROUND: Recent evidence has implicated the MAP kinase (MAPK) pathway with the development of castrate-resistant prostate cancer (CRPC). We have previously reported gene amplification of critical members of this pathway with the development of castrate-resistant disease. In addition, we have shown that rising Raf-1 expression, with the development of CRPC, influences time to biochemical relapse. We therefore sought to further analyse the role of both Raf-1 and its downstream target MAPK in the molecular pathogenesis of CRPC. METHODS: Protein expression of Raf-1 and MAPK, including their activation status, was analysed using immunohistochemistry in a database of 65 paired tumour specimens obtained before and after the development of CRPC and correlated with other members of the pathway. RESULTS: Patients whose nuclear expression of MAPK rose with the development of CRPC had a significantly shorter median time to death following biochemical relapse (1.40 vs 3.00 years, P=0.0255) as well as reduced disease-specific survival when compared with those whose expression fell or remained unchanged (1.16 vs 2.62 years, P=0.0005). Significant correlations were observed between protein expression of Raf-1 and MAPK with the type 1 receptor tyrosine kinases, Her2 and epidermal growth factor receptor, as well as the transcription factor AP-1 in CRPC tumours. CONCLUSION: We conclude that the Her2/Raf-1/MAPK/AP-1 axis may promote the development of CRPC, leading to early relapse, and reduced disease-specific survival. In addition, members of the pathway may act as novel therapeutic and/or diagnostic targets for prostate cancer. British Journal of Cancer (2011) 104, 1920-1928. doi:10.1038/bjc.2011.163 www.bjcancer.com Published online 10 May 2011 (C) 2011 Cancer Research U

Notulae to the Italian native vascular flora: 1

In this contribution, new data concerning the Italian distribution of native vascular flora are presented. It includes new records, exclusions, and confirmations pertaining to the Italian administrative regions for taxa in the genera Arundo, Bromopsis, Cistus, Crocus, Festuca, Galeopsis, Genista, Lamium, Leucanthemum, Nerium, Orobanche, Peucedanum, Pilosella, Polycnemum, Stipa and Viola

Switching to dual/monotherapy determines an increase in CD8+ in HIV-infected individuals: An observational cohort study

Background: The CD4/CD8 ratio has been associated with the risk of AIDS and non-AIDS events. We describe trends in immunological parameters in people who underwent a switch to monotherapy or dual therapy, compared to a control group remaining on triple antiretroviral therapy (ART). Methods: We included patients in Icona who started a three-drug combination ART regimen from an ART-naïve status and achieved a viral load ≤ 50 copies/mL; they were subsequently switched to another triple or to a mono or double regimen. Standard linear regression at fixed points in time (12-24 months after the switch) and linear mixed model analysis with random intercepts and slopes were used to compare CD4 and CD8 counts and their ratio over time according to regimen types (triple vs. dual and vs. mono). Results: A total of 1241 patients were included; 1073 switched to triple regimens, 104 to dual (72 with 1 nucleoside reverse transcriptase inhibitor (NRTI), 32 NRTI-sparing), and 64 to monotherapy. At 12 months after the switch, for the multivariable linear regression the mean change in the log10 CD4/CD8 ratio for patients on dual therapy was -0.03 (95% confidence interval (CI) -0.05, -0.0002), and the mean change in CD8 count was +99 (95% CI +12.1, +186.3), taking those on triple therapy as reference. In contrast, there was no evidence for a difference in CD4 count change. When using all counts, there was evidence for a significant difference in the slope of the ratio and CD8 count between people who were switched to triple (points/year change ratio = +0.056, CD8 = -25.7) and those to dual regimen (ratio = -0.029, CD8 = +110.4). Conclusions: We found an increase in CD8 lymphocytes in people who were switched to dual regimens compared to those who were switched to triple. Patients on monotherapy did not show significant differences. The long-term implications of this difference should be ascertained

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2