235 research outputs found
Prespecified Risk Criteria Facilitate Adequate Discharge and LongâTerm Outcomes After Transfemoral Transcatheter Aortic Valve Implantation
Background
Despite the availability of guidelines for the performance of transcatheter aortic valve implantation (TAVI), current treatment pathways vary between countries and institutions, which impact on the mean duration of postprocedure hospitalization.
Methods and Results
This was a prospective, multicenter registry of 502 patients to validate the appropriateness of discharge timing after transfemoral TAVI, using prespecified risk criteria from FASTâTAVI (Feasibility and Safety of Early Discharge After Transfemoral [TF] Transcatheter Aortic Valve Implantation), based on hospital events within 1âyear after discharge. The end pointâa composite of allâcause mortality, vascular accessârelated complications, permanent pacemaker implantation, stroke, cardiac rehospitalization, kidney failure, and major bleedingâwas reached in 27.0% of patients (95% CI, 23.3â31.2) within 1 year after intervention; 7.5% (95% CI, 5.5â10.2) had inâhospital complications before discharge and 19.6% (95% CI, 16.3â23.4) within 1 year after discharge. Overall mortality within 1 year after discharge was 7.3% and rates of cardiac rehospitalization 13.5%, permanent pacemaker implantation 4.2%, any stroke 1.8%, vascularâaccessârelated complications 0.7%, lifeâthreatening bleeding 0.7%, and kidney failure 0.4%. Composite events within 1 year after discharge were observed in 18.8% and 24.3% of patients with low risk of complications/early (â€3 days) discharge and high risk and discharged late (>3 days) (concordant discharge), respectively. Event rate in patients with discordant discharge was 14.3% with low risk but discharged late and increased to 50.0% in patients with high risk but discharged in â€3 days.
Conclusions
The FASTâTAVI risk assessment provides a tool for appropriate, riskâbased discharge that was validated with the 1âyear event rate after transfemoral TAVI.
Registration
URL:
https://www.ClinicalTrials.gov
; Unique identifier: NCT02404467
Prion protein amyloidosis with divergent phenotype associated with two novel nonsense mutations in PRNP
Stop codon mutations in the gene encoding the prion protein (PRNP) are very rare and have thus far only been described in two patients with prion protein cerebral amyloid angiopathy (PrP-CAA). In this report, we describe the clinical, histopathological and pathological prion protein (PrPSc) characteristics of two Dutch patients carrying novel adjacent stop codon mutations in the C-terminal part of PRNP, resulting in either case in hereditary prion protein amyloidoses, but with strikingly different clinicopathological phenotypes. The patient with the shortest disease duration (27 months) carried a Y226X mutation and showed PrP-CAA without any neurofibrillary lesions, whereas the patient with the longest disease duration (72 months) had a Q227X mutation and showed an unusual Gerstmann-StrÀussler-Scheinker disease phenotype with numerous cerebral multicentric amyloid plaques and severe neurofibrillary lesions without PrP-CAA. Western blot analysis in the patient with the Q227X mutation demonstrated the presence of a 7 kDa unglycosylated PrPSc fragment truncated at both the N- and C-terminal ends. Our observations expand the spectrum of clinicopathological phenotypes associated with PRNP mutations and show that a single tyrosine residue difference in the PrP C-terminus may significantly affect the site of amyloid deposition and the overall phenotypic expression of the prion disease. Furthermore, it confirms that the absence of the glycosylphosphatidylinositol anchor in PrP predisposes to amyloid plaque formation
Altered Risk-Based Decision Making following Adolescent Alcohol Use Results from an Imbalance in Reinforcement Learning in Rats
Alcohol use during adolescence has profound and enduring consequences on decision-making under risk. However, the fundamental psychological processes underlying these changes are unknown. Here, we show that alcohol use produces over-fast learning for better-than-expected, but not worse-than-expected, outcomes without altering subjective reward valuation. We constructed a simple reinforcement learning model to simulate altered decision making using behavioral parameters extracted from rats with a history of adolescent alcohol use. Remarkably, the learning imbalance alone was sufficient to simulate the divergence in choice behavior observed between these groups of animals. These findings identify a selective alteration in reinforcement learning following adolescent alcohol use that can account for a robust change in risk-based decision making persisting into later life
Darwin's Duchenne: Eye constriction during infant joy and distress
Darwin proposed that smiles with eye constriction (Duchenne smiles) index strong positive emotion in infants, while cry-faces with eye constriction index strong negative emotion. Research has supported Darwin's proposal with respect to smiling, but there has been little parallel research on cry-faces (open-mouth expressions with lateral lip stretching). To investigate the possibility that eye constriction indexes the affective intensity of positive and negative emotions, we first conducted the Face-to-Face/Still-Face (FFSF) procedure at 6 months. In the FFSF, three minutes of naturalistic infant-parent play interaction (which elicits more smiles than cry-faces) are followed by two minutes in which the parent holds an unresponsive still-face (which elicits more cry-faces than smiles). Consistent with Darwin's proposal, eye constriction was associated with stronger smiling and with stronger cry-faces. In addition, the proportion of smiles with eye constriction was higher during the positive-emotion eliciting play episode than during the still-face. In parallel, the proportion of cry-faces with eye constriction was higher during the negative-emotion eliciting still-face than during play. These results are consonant with the hypothesis that eye constriction indexes the affective intensity of both positive and negative facial configurations. A preponderance of eye constriction during cry-faces was observed in a second elicitor of intense negative emotion, vaccination injections, at both 6 and 12 months of age. The results support the existence of a Duchenne distress expression that parallels the more well-known Duchenne smile. This suggests that eye constriction-the Duchenne marker-has a systematic association with early facial expressions of intense negative and positive emotion. © 2013 Mattson et al
Cerium Oxide Nanoparticles Protect Cardiac Progenitor Cells from Oxidative Stress
Cardiac progenitor cells (CPCs) are a promising autologous source of cells for cardiac
regenerative medicine. However, CPC culture in vitro requires the presence of microenvironmental
conditions (a complex array of bioactive substance concentration, mechanostructural
factors, and physicochemical factors) closely mimicking the natural cell surrounding in vivo,
including the capability to uphold reactive oxygen species (ROS) within physiological levels
in vitro. Cerium oxide nanoparticles (nanoceria) are redox-active and could represent a potent
tool to control the oxidative stress in isolated CPCs. Here, we report that 24 h exposure to 5, 10,
and 50 !g/mL of nanoceria did not a!ect cell growth and function in cardiac progenitor cells,
while being able to protect CPCs from H2O2-induced cytotoxicity for at least 7 days, indicating
that nanoceria in an e!ective antioxidant. Therefore, these "ndings con"rm the great
potential of nanoceria for controlling ROS-induced cell damage
EMU Detection of a Large and Low Surface Brightness Galactic SNR G288.8-6.3
We present the serendipitous detection of a new Galactic Supernova Remnant
(SNR), G288.8-6.3 using data from the Australian Square Kilometre Array
Pathfinder (ASKAP)-Evolutionary Map of the Universe (EMU) survey. Using
multi-frequency analysis, we confirm this object as an evolved Galactic SNR at
high Galactic latitude with low radio surface brightness and typical SNR
spectral index of . To determine the magnetic field
strength in SNR G288.8-6.3, we present the first derivation of the
equipartition formulae for SNRs with spectral indices . The
angular size is 1.\!^\circ 8\times 1.\!^\circ 6 (107.\!^\prime 6 \times
98.\!^\prime 4) and we estimate that its intrinsic size is pc which
implies a distance of kpc and a position of pc above the
Galactic plane. This is one of the largest angular size and closest Galactic
SNRs. Given its low radio surface brightness, we suggest that it is about 13000
years old.Comment: Accepted for publication in The Astrophysical Journa
Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis
BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London
Towards the introduction of the âImmunoscoreâ in the classification of malignant tumours
The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression-based stratification. These parameters rely on tumour-cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named âImmunoscoreâ has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune). © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland
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