Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea

Background Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure. Methods Between May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2 months. Arterial blood gas parameters, clinical symptoms, health-related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis. Results A total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of -6 (95% CI -7.7 to -4.2) mm Hg versus -2.8 (95% CI -4.3 to -1.3) mm Hg, (p<0.001) and serum bicarbonate of -3.4 (95% CI -4.5 to -2.3) versus -1 (95% CI -1.7 to -0.2 95% CI) mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group. Conclusions NIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long-term prospective studies are necessary to determine whether NIV reduces healthcare resource utilisation, cardiovascular events and mortality

The adenylyl cyclase Rv2212 modifies the proteome and infectivity of Mycobacterium bovis BCG

All organisms have the capacity to sense and respond to environmental changes. These signals often involve the use of second messengers such as cyclic adenosine monophosphate (cAMP). This second messenger is widely distributed among organisms and coordinates gene expression related with pathogenesis, virulence, and environmental adaptation. Genomic analysis in Mycobacterium tuberculosis has identified 16 adenylyl cyclases (AC) and one phosphodiesterase, which produce and degrade cAMP, respectively. To date, ten AC have been biochemically characterized and only one (Rv0386) has been found to be important during murine infection with M. tuberculosis. Here, we investigated the impact of hsp60-driven Rv2212 gene expression in Mycobacterium bovis Bacillus Calmette-Guerin (BCG) during growth in vitro, and during macrophage and mice infection. We found that hsp60-driven expression of Rv2212 resulted in an increased capacity of replication in murine macrophages but an attenuated phenotype in lungs and spleen when administered intravenously in mice. Furthermore, this strain displayed an altered proteome mainly affecting proteins associated with stress conditions (bfrB, groEL-2, DnaK) that could contribute to the attenuated phenotype observed in mice. © 2014, Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i

A new animal model of atrophy–hypertrophy complex and liver damage followingYttrium‐90 lobar selective internal radiation therapy in rabbits

Lobar selective internal radiation therapy (SIRT) is widely used to treat liver tumors inducing atrophy of the treated lobe and contralateral hypertrophy. The lack of animal model has precluded further investigations to improve this treatment. We developed an animal model of liver damage and atrophy–hypertrophy complex after SIRT. Three groups of 5–8 rabbits received transportal SIRT with Yttrium 90 resin microspheres of the cranial lobes with diferent activities (0.3, 0.6 and 1.2GBq), corresponding to predicted absorbed radiation dose of 200, 400 and 800 Gy, respectively. Another group received non-loaded microspheres (sham group). Cranial and caudal lobes volumes were assessed using CT volumetry before, 15 and 30 days after SIRT. Liver biochemistry, histopathology and gene expression were evaluated. Four untreated rabbits were used as controls for gene expression studies. All animals receiving 1.2GBq were euthanized due to clinical deterioration. Cranial SIRT with 0.6GBq induced caudal lobe hypertrophy after 15 days (median increase 34% -ns-) but produced signifcant toxicity. Cranial SIRT with 0.3GBq induced caudal lobe hypertrophy after 30 days (median increase 82%, p = 0.04). No volumetric changes were detected in sham group. Transient increase in serum transaminases was detected in all treated groups returning to normal values at 15 days. There was dose-dependent liver dysfunction with bilirubin elevation and albumin decrease. Histologically, 1.2GBq group developed permanent severe liver damage with massive necrosis, 0.6 and 0.3GBq groups developed moderate damage with infammation and portal fbrosis at 15 days, partially recovering at 30 days. There was no diference in the expression of hepatocyte function and diferentiation genes between 0.3GBq and control groups. Cranial SIRT with 0.3GBq of 90Y resin microspheres in rabbits is a reliable animal model to analyse the atrophy–hypertrophy complex and liver damage without toxicity

The effects of electron cyclotron heating and current drive on toroidal Alfvén eigenmodes in tokamak plasmas

Dedicated studies performed for toroidal Alfvén eigenmodes (TAEs) in ASDEX-Upgrade (AUG) discharges with monotonic q-profiles have shown that electron cyclotron resonance heating (ECRH) can make TAEs more unstable. In these AUG discharges, energetic ions driving TAEs were obtained by ion cyclotron resonance heating (ICRH). It was found that off-axis ECRH facilitated TAE instability, with TAEs appearing and disappearing on timescales of a few milliseconds when the ECRH power was switched on and off. On-axis ECRH had a much weaker effect on TAEs, and in AUG discharges performed with co- and counter-current electron cyclotron current drive (ECCD), the effects of ECCD were found to be similar to those of ECRH. Fast ion distributions produced by ICRH were computed with the PION and SELFO codes. A significant increase in T e caused by ECRH applied off-axis is found to increase the fast ion slowing-down time and fast ion pressure causing a significant increase in the TAE drive by ICRH-accelerated ions. TAE stability calculations show that the rise in T e causes also an increase in TAE radiative damping and thermal ion Landau damping, but to a lesser extent than the fast ion drive. As a result of the competition between larger drive and damping effects caused by ECRH, TAEs become more unstable. It is concluded, that although ECRH effects on AE stability in present-day experiments may be quite significant, they are determined by the changes in the plasma profiles and are not particularly ECRH specific.This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014-2018 under grant agreement No 633053 and from the RCUK Energy Programme [grant number EP/P012450/1]. The views and opinions expressed herein do not necessarily reflect those of the European Commission.Peer Reviewe

The effects of electron cyclotron heating and current drive on toroidal Alfvén eigenmodes in tokamak plasmas

Dedicated studies performed for toroidal Alfvén eigenmodes (TAEs) in ASDEX-Upgrade (AUG) discharges with monotonic q-profiles have shown that electron cyclotron resonance heating (ECRH) can make TAEs more unstable. In these AUG discharges, energetic ions driving TAEs were obtained by ion cyclotron resonance heating (ICRH). It was found that off-axis ECRH facilitated TAE instability, with TAEs appearing and disappearing on timescales of a few milliseconds when the ECRH power was switched on and off. On-axis ECRH had a much weaker effect on TAEs, and in AUG discharges performed with co- and counter-current electron cyclotron current drive (ECCD), the effects of ECCD were found to be similar to those of ECRH. Fast ion distributions produced by ICRH were computed with the PION and SELFO codes. A significant increase in T e caused by ECRH applied off-axis is found to increase the fast ion slowing-down time and fast ion pressure causing a significant increase in the TAE drive by ICRH-accelerated ions. TAE stability calculations show that the rise in T e causes also an increase in TAE radiative damping and thermal ion Landau damping, but to a lesser extent than the fast ion drive. As a result of the competition between larger drive and damping effects caused by ECRH, TAEs become more unstable. It is concluded, that although ECRH effects on AE stability in present-day experiments may be quite significant, they are determined by the changes in the plasma profiles and are not particularly ECRH specific.This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014-2018 under grant agreement No 633053 and from the RCUK Energy Programme [grant number EP/P012450/1]. The views and opinions expressed herein do not necessarily reflect those of the European Commission.Peer ReviewedPostprint (author's final draft

The effects of electron cyclotron heating and current drive on toroidal Alfvén eigenmodes in tokamak plasmas

Dedicated studies performed for toroidal Alfvén eigenmodes (TAEs) in ASDEX-Upgrade (AUG) discharges with monotonic q-profiles have shown that electron cyclotron resonance heating (ECRH) can make TAEs more unstable. In these AUG discharges, energetic ions driving TAEs were obtained by ion cyclotron resonance heating (ICRH). It was found that off-axis ECRH facilitated TAE instability, with TAEs appearing and disappearing on timescales of a few milliseconds when the ECRH power was switched on and off. On-axis ECRH had a much weaker effect on TAEs, and in AUG discharges performed with co- and counter-current electron cyclotron current drive (ECCD), the effects of ECCD were found to be similar to those of ECRH. Fast ion distributions produced by ICRH were computed with the PION and SELFO codes. A significant increase in T e caused by ECRH applied off-axis is found to increase the fast ion slowing-down time and fast ion pressure causing a significant increase in the TAE drive by ICRH-accelerated ions. TAE stability calculations show that the rise in T e causes also an increase in TAE radiative damping and thermal ion Landau damping, but to a lesser extent than the fast ion drive. As a result of the competition between larger drive and damping effects caused by ECRH, TAEs become more unstable. It is concluded, that although ECRH effects on AE stability in present-day experiments may be quite significant, they are determined by the changes in the plasma profiles and are not particularly ECRH specific.This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014-2018 under grant agreement No 633053 and from the RCUK Energy Programme [grant number EP/P012450/1]. The views and opinions expressed herein do not necessarily reflect those of the European Commission.Peer Reviewe

A noninterventional study to monitor patients with diabetic macular oedema starting treatment with ranibizumab (POLARIS)

Purpose: Antivascular endothelial growth factor agents are increasingly used in diabetic macular oedema (DME); however, there are few studies exploring their use in DME in real-world settings. Methods: POLARIS was a noninterventional, multicentre study to monitor 12-month outcomes in patients starting ranibizumab treatment in routine practices. The primary outcome was mean change in visual acuity (VA) from baseline to month 12 (last observation carried forward approach). Other outcomes included mean change in central retinal thickness (CRT) and resource utilization. Visual acuity (VA) outcomes were also stratified by country, baseline visual acuity score (VAS), sex, age and injection frequency. Results: Outcomes were analysed from all treated patients (n = 804) and from first-year completers (patients who had a visual acuity assessment at 12 months; n = 568). The mean (SD) baseline VAS was 59.4 (15.9) letters, and the mean change in visual acuity was 4.4 letters (95% confidence interval: 3.3–5.4) at month 12 (study eye; first-year completers). The mean number of injections (study eye) was 4.9, and the mean number of all visits (any eye) was 10 (58% were injection visits) over 12 months (first-year completers). The mean (SD) baseline CRT was 410.6 (128.8) μm, and the mean change in CRT was −115.2 μm at month 12 (study eye; first-year completers). Visual acuity (VA) outcomes were generally comparable across most countries and subgroups and were greatest in patients with the lowest baseline VAS (≤60 letters). Conclusion: POLARIS showed that real-world outcomes in DME patients starting treatment with ranibizumab were lower than those observed in clinical studies, in spite of extensive monitoring. © 2018 The Authors. Acta Ophthalmologica published by John Wiley &amp; Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation

Correction to: Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study

Correction to: Intensive Care Med (2016) 42:1865\u20131876 DOI 10.1007/s00134-016-4571-

Resolved versus confirmed ARDS after 24&#160;h: insights from the LUNG SAFE study

Purpose: To evaluate patients with resolved versus confirmed ARDS, identify subgroups with substantial mortality risk, and to determine the utility of day 2 ARDS reclassification. Methods: Our primary objective, in this secondary LUNG SAFE analysis, was to compare outcome in patients with resolved versus confirmed ARDS after 24\ua0h. Secondary objectives included identifying factors associated with ARDS persistence and mortality, and the utility of day 2 ARDS reclassification. Results: Of 2377 patients fulfilling the ARDS definition on the first day of ARDS (day 1) and receiving invasive mechanical ventilation, 503 (24%) no longer fulfilled the ARDS definition the next day, 52% of whom initially had moderate or severe ARDS. Higher tidal volume on day 1 of ARDS was associated with confirmed ARDS [OR 1.07 (CI 1.01\u20131.13), P = 0.035]. Hospital mortality was 38% overall, ranging from 31% in resolved ARDS to 41% in confirmed ARDS, and 57% in confirmed severe ARDS at day 2. In both\ua0resolved and confirmed\ua0ARDS, age, non-respiratory SOFA score, lower PEEP and P/F ratio, higher peak pressure and respiratory rate were each\ua0associated with mortality. In confirmed ARDS, pH and the presence of immunosuppression or neoplasm were also associated\ua0with mortality. The increase in area under the receiver operating curve for ARDS reclassification on day 2 was marginal. Conclusions: ARDS, whether resolved or confirmed at day 2, has a high mortality rate. ARDS reclassification at day 2 has limited predictive value for mortality. The substantial mortality risk in severe confirmed ARDS suggests that complex interventions might best be tested in this population. Trial Registration: ClinicalTrials.gov NCT02010073. \ua9 2018, Springer-Verlag GmbH Germany, part of Springer Nature and ESICM