Lung transplantation in patients 70 years old or older: Have outcomes changed after implementation of the lung allocation score?

ObjectiveThe objective of the present study was to evaluate whether the outcomes of lung transplantation in patients aged 70 years or older have changed after implementation of the lung allocation score in May 2005.MethodsPatients aged 70 years or older undergoing primary lung transplantation from 1995 to 2009 were identified from the United Network for Organ Sharing registry. The primary stratification was the pre-lung allocation score era versus lung allocation score era. Risk-adjusted multivariate Cox regression and Kaplan-Meier analyses were conducted to evaluate the effect of age 70 years or older on 1-year post-transplant mortality compared with a reference cohort of patients aged 60 to 69 years.ResultsOf the overall 15,726 adult lung transplantation patients in the study period, 225 (1.4%) were 70 years old or older and 4634 (29.5%) were 60 to 69 years old. The patients aged 70 years or older were a larger cohort of overall lung transplantation patients in the lung allocation score era compared with before the lung allocation score era (3.1% vs 0.3%, P < .001). In the risk-adjusted Cox analysis, age 70 years or older was a significant risk factor for 1-year post-lung transplantation mortality in the pre-lung allocation score era (hazard ratio, 2.00; 95% confidence interval, 1.10-3.62, P = .02) but not in the lung allocation score era (hazard ratio, 1.02; 95% confidence interval, 0.71-1.46; P = .92). Similarly, Kaplan-Meier 1-year survival was significantly reduced in patients 70 years old or older versus 60 to 69 years old in the pre-lung allocation score era (56.7% vs 76.3%, P = .006) but not in the lung allocation score era (79.0% vs 80.0%, P = .72).ConclusionsRecipients aged 70 years or older were a larger proportion of overall lung transplantation patients after implementation of the lung allocation score. Although associated with significantly increased post-lung transplantation mortality in the pre-lung allocation score era, age 70 years or older is currently associated with outcomes comparable to those of patients aged 60 to 69 years. Therefore, age 70 years or older should not serve as an absolute contraindication to lung transplantation in the lung allocation score era

Effets de l'enrichissement en oxygène sur une flamme turbulente non-prémélangée, méthane-air, stabilisée par un swirl

Ce travail présente les effets de l’enrichissement en oxygène sur le comportement d’une flamme non-prémélangée méthane air dans un brûleur co-axial à swirl. L’étude porte plus particulièrement sur la stabilité de la flamme et les émissions polluantes telles que les NOx, CO2, CO et CH4. Les expériences sont menées dans une chambre de combustion cylindrique de 25 kW refroidie par une circulation d’eau. Le brûleur est constitué de deux tubes concentriques avec un swirl placé dans la partie annulaire afin de mettre en rotation l’oxydant. Le tube central achemine le méthane jusqu’à un injecteur radial qui comporte huit trous uniformément répartis situés juste en dessous du plan de sortie du brûleur. Les mesures des gaz brûlés sont effectuées par des analyseurs multi-gaz à l’aide d’une sonde de prélèvement en sortie de la chambre de combustion. Des expériences de chimiluminescence du radical OH* sont menées pour décrire la structure et la stabilité de la flamme dans les cas air et air enrichi en oxygène. Les hauteurs d’accrochage, les fluctuations de la base de la flamme, et les longueurs de flamme sont déterminées. Les mesures sont effectuées pour une concentration en oxygène qui varie de 0 à 40 % en volume, un nombre de swirl de 0,8 à 1,4 et une richesse globale de 0,7 à 1. Les résultats montrent que l’ajout de l’oxygène à l’air améliorent la stabilité de la flamme en étendant les limites de soufflage. L’augmentation de la concentration en oxygène conduit à une diminution des hauteurs de décrochage et une réduction des fluctuations de la base de la flamme. Les mesures ont montré que l’augmentation du nombre de swirl améliore significativement la stabilité de la flamme. L’analyse des gaz brûlés a révélé que les émissions de CO2 augmentent linéairement avec la concentration en oxygène. Les émissions de CO décroissent exponentiellement tandis que les émissions de NOx, augmentent exponentiellement avec l’enrichissement en oxygène

Loss of NOTCH2 Positively Predicts Survival in Subgroups of Human Glial Brain Tumors

The structural complexity of chromosome 1p centromeric region has been an obstacle for fine mapping of tumor suppressor genes in this area. Loss of heterozygosity (LOH) on chromosome 1p is associated with the longer survival of oligodendroglioma (OD) patients. To test the clinical relevance of 1p loss in glioblastomas (GBM) patients and identifiy the underlying tumor suppressor locus, we constructed a somatic deletion map on chromosome 1p in 26 OG and 118 GBM. Deletion hotspots at 4 microsatellite markers located at 1p36.3, 1p36.1, 1p22 and 1p11 defined 10 distinct haplotypes that were related to patient survival. We found that loss of 1p centromeric marker D1S2696 within NOTCH2 intron 12 was associated with favorable prognosis in OD (P = 0.0007) as well as in GBM (P = 0.0175), while 19q loss, concomitant with 1p LOH in OD, had no influence on GBM survival (P = 0.918). Assessment of the intra-chromosomal ratio between NOTCH2 and its 1q21 pericentric duplication N2N (N2/N2N-test) allowed delineation of a consistent centromeric breakpoint in OD that also contained a minimally lost area in GBM. OD and GBM showed distinct deletion patterns that converged to the NOTCH2 gene in both glioma subtypes. Moreover, the N2/N2N-test disclosed homozygous deletions of NOTCH2 in primary OD. The N2/N2N test distinguished OD from GBM with a specificity of 100% and a sensitivity of 97%. Combined assessment of NOTCH2 genetic markers D1S2696 and N2/N2N predicted 24-month survival with an accuracy (0.925) that is equivalent to histological classification combined with the D1S2696 status (0.954) and higher than current genetic evaluation by 1p/19q LOH (0.762). Our data propose NOTCH2 as a powerful new molecular test to detect prognostically favorable gliomas

Evaluation of the 2021 ESC recommendations for family screening in hereditary transthyretin cardiac amyloidosis

AIMS: The 2021 European Society of Cardiology (ESC) screening recommendations for individuals carrying a pathogenic transthyretin amyloidosis variant (ATTRv) are based on expert opinion. We aimed to (i) determine the penetrance of ATTRv cardiomyopathy (ATTRv-CM) at baseline; (ii) examine the value of serial evaluation; and (iii) establish the yield of first-line diagnostic tests (i.e. electrocardiogram, echocardiogram, and laboratory tests) as per 2021 ESC position statement.METHODS AND RESULTS: We included 159 relatives (median age 55.6 [43.2-65.9] years, 52% male) at risk for ATTRv-CM from 10 centres. The primary endpoint, ATTRv-CM diagnosis, was defined as the presence of (i) cardiac tracer uptake in bone scintigraphy; or (ii) transthyretin-positive cardiac biopsy. The secondary endpoint was a composite of heart failure (New York Heart Association class ≥II) and pacemaker-requiring conduction disorders. At baseline, 40/159 (25%) relatives were diagnosed with ATTRv-CM. Of those, 20 (50%) met the secondary endpoint. Indication to screen (≤10 years prior to predicted disease onset and absence of extracardiac amyloidosis) had an excellent negative predictive value (97%). Other pre-screening predictors for ATTRv-CM were infrequently identified variants and male sex. Importantly, 13% of relatives with ATTRv-CM did not show any signs of cardiac involvement on first-line diagnostic tests. The yield of serial evaluation (n = 41 relatives; follow-up 3.1 [2.2-5.2] years) at 3-year interval was 9.4%.CONCLUSIONS: Screening according to the 2021 ESC position statement performs well in daily clinical practice. Clinicians should adhere to repeating bone scintigraphy after 3 years, as progressing to ATTRv-CM without signs of ATTRv-CM on first-line diagnostic tests or symptoms is common.</p

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

Transcription Factor NF-κB Is Transported to the Nucleus via Cytoplasmic Dynein/Dynactin Motor Complex in Hippocampal Neurons

Mikenberg I, Widera D, Kaus A, Kaltschmidt B, Kaltschmidt C. Transcription Factor NF-kappa B Is Transported to the Nucleus via Cytoplasmic Dynein/Dynactin Motor Complex in Hippocampal Neurons. PLOS ONE. 2007;2(7):e589.Background. Long-term changes in synaptic plasticity require gene transcription, indicating that signals generated at the synapse must be transported to the nucleus. Synaptic activation of hippocampal neurons is known to trigger retrograde transport of transcription factor NF-kappa B. Transcription factors of the NF-kappa B family are widely expressed in the nervous system and regulate expression of several genes involved in neuroplasticity, cell survival, learning and memory. Principal Findings. In this study, we examine the role of the dynein/dynactin motor complex in the cellular mechanism targeting and transporting activated NF-kappa B to the nucleus in response to synaptic stimulation. We demonstrate that overexpression of dynamitin, which is known to dissociate dynein from microtubules, and treatment with microtubule-disrupting drugs inhibits nuclear accumulation of NF-kappa B p65 and reduces NF-kappa B-dependent transcription activity. In this line, we show that p65 is associated with components of the dynein/dynactin complex in vivo and in vitro and that the nuclear localization sequence (NLS) within NF-kappa B p65 is essential for this binding. Conclusion. This study shows the molecular mechanism for the retrograde transport of activated NF-kappa B from distant synaptic sites towards the nucleus

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns