Efficacy and safety of the combination of reduced duration prophylaxis followed by immuno-guided prophylaxis to prevent cytomegalovirus disease in lung transplant recipients (CYTOCOR STUDY) : An open-label, randomised, non-inferiority clinical trial

Introduction Prolonged use of antivirals to prevent the development of cytomegalovirus (CMV) disease in lung transplant patients has been shown to have significant side effects, for which alternatives are being sought to reduce their use. The monitoring of cell immunity against CMV could be an alternative as it has shown to be useful in identifying transplant patients at low risk of infection, who could benefit from shorter prophylaxis. The aim of the CYTOCOR study is to demonstrate that the combination of a reduced prophylaxis strategy with subsequent CMV-specific immunological monitoring would allow CMV infection to be controlled in lung transplant patients as effectively as the usual strategy (prophylaxis followed by pre-emptive therapy), while reducing the side effects of antivirals due to the shorter duration of prophylaxis. Methods and analysis Phase III randomised, open, multicentre, parallel, non-inferiority clinical trial to study the efficacy and safety of the combination of a prophylaxis strategy up to month +3 post-transplant followed by immuno-guided prophylaxis using the QuantiFERON-CMV technique up to month +12 post-transplant to prevent CMV disease in CMV-seropositive lung transplant recipients. This strategy will be compared with a combination of a usual prophylaxis strategy up to month +6 post-transplant followed by pre-emptive therapy up to month +12. To study the incidence of CMV disease, patients will be followed up to 18 months post-transplantation. A total of 150 patients are expected to be recruited for the study. Ethics and public dissemination The clinical trial has been approved by the Research Ethics Committees and authorised by the Spanish Agency of Medicines and Medical Devices (AEMPS). If the hypothesis of this clinical trial is verified, the dissemination of the results could change clinical practice by increasing knowledge about the safety and efficacy of discontinuing valganciclovir prophylaxis in lung transplant recipients. Trial registration number NCT03699254

Efficacy and safety of the combination of reduced duration prophylaxis followed by immuno-guided prophylaxis to prevent cytomegalovirus disease in lung transplant recipients (CYTOCOR STUDY): an open-label, randomised, non-inferiority clinical trial.

INTRODUCTION: Prolonged use of antivirals to prevent the development of cytomegalovirus (CMV) disease in lung transplant patients has been shown to have significant side effects, for which alternatives are being sought to reduce their use. The monitoring of cell immunity against CMV could be an alternative as it has shown to be useful in identifying transplant patients at low risk of infection, who could benefit from shorter prophylaxis. The aim of the CYTOCOR study is to demonstrate that the combination of a reduced prophylaxis strategy with subsequent CMV-specific immunological monitoring would allow CMV infection to be controlled in lung transplant patients as effectively as the usual strategy (prophylaxis followed by pre-emptive therapy), while reducing the side effects of antivirals due to the shorter duration of prophylaxis. METHODS AND ANALYSIS: Phase III randomised, open, multicentre, parallel, non-inferiority clinical trial to study the efficacy and safety of the combination of a prophylaxis strategy up to month +3 post-transplant followed by immuno-guided prophylaxis using the QuantiFERON-CMV technique up to month +12 post-transplant to prevent CMV disease in CMV-seropositive lung transplant recipients. This strategy will be compared with a combination of a usual prophylaxis strategy up to month +6 post-transplant followed by pre-emptive therapy up to month +12. To study the incidence of CMV disease, patients will be followed up to 18 months post-transplantation. A total of 150 patients are expected to be recruited for the study. ETHICS AND PUBLIC DISSEMINATION: The clinical trial has been approved by the Research Ethics Committees and authorised by the Spanish Agency of Medicines and Medical Devices (AEMPS).If the hypothesis of this clinical trial is verified, the dissemination of the results could change clinical practice by increasing knowledge about the safety and efficacy of discontinuing valganciclovir prophylaxis in lung transplant recipient

Role of MUC1 rs4072037 polymorphism and serum KL-6 levels in patients with antisynthetase syndrome

Mucin 1/Krebs von den Lungen-6 (KL-6) is proposed as a serum biomarker of several interstitial lung diseases (ILDs), including connective tissue disorders associated with ILD. However, it has not been studied in a large cohort of Caucasian antisynthetase syndrome (ASSD) patients. Consequently, we assessed the role of MUC1 rs4072037 and serum KL-6 levels as a potential biomarker of ASSD susceptibility and for the differential diagnosis between patients with ILD associated with ASSD (ASSD-ILD +) and idiopathic pulmonary fibrosis (IPF). 168 ASSD patients (149 ASSD-ILD +), 174 IPF patients and 523 healthy controls were genotyped for MUC1 rs4072037 T > C. Serum KL-6 levels were determined in a subgroup of individuals. A significant increase of MUC1 rs4072037 CC genotype and C allele frequencies was observed in ASSD patients compared to healthy controls. Likewise, MUC1 rs4072037 TC and CC genotypes and C allele frequencies were significantly different between ASSD-ILD+ and IPF patients. Additionally, serum KL-6 levels were significantly higher in ASSD patients compared to healthy controls. Nevertheless, no differences in serum KL-6 levels were found between ASSD-ILD+ and IPF patients. Our results suggest that the presence of MUC1 rs4072037 C allele increases the risk of ASSD and it could be a useful genetic biomarker for the differential diagnosis between ASSD-ILD+ and IPF patients

Proton acceleration in thermonuclear nova explosions revealed by gamma ray

Classical novae are cataclysmic binary star systems in which the matter of a companion star is accreted on a white dwarf (WD). Accumulation of the matter in a layer eventually causes a thermonuclear explosion on the surface of the WD, brightening the WD to ~ 10 5 solar luminosities and triggering ejection of the accumulated matter. They provide extreme conditions required to accelerate particles, electrons or protons, to high energies. Here we present the detection of gamma rays by the MAGIC telescopes from the 2021 outburst of RS Ophiuchi (RS Oph), a recurrent symbiotic nova, that allowed us, for the first time, to accurately characterize the emission from a nova in the 60 GeV to 250 GeV energy range. The theoretical interpretation of the combined Fermi -LAT and MAGIC data suggests that protons are accelerated to hundreds of GeV in the nova shock. Such protons should create bubbles of enhanced Cosmic Ray density up to about 13 pc from the recurrent novae

Proton acceleration in thermonuclear nova explosions revealed by gamma rays

International audienceClassical novae are cataclysmic binary star systems in which the matter of a companion star is accreted on a white dwarf (WD). Accumulation of the matter in a layer eventually causes a thermonuclear explosion on the surface of the WD, brightening the WD to ~ 10 5 solar luminosities and triggering ejection of the accumulated matter. They provide extreme conditions required to accelerate particles, electrons or protons, to high energies. Here we present the detection of gamma rays by the MAGIC telescopes from the 2021 outburst of RS Ophiuchi (RS Oph), a recurrent symbiotic nova, that allowed us, for the first time, to accurately characterize the emission from a nova in the 60 GeV to 250 GeV energy range. The theoretical interpretation of the combined Fermi -LAT and MAGIC data suggests that protons are accelerated to hundreds of GeV in the nova shock. Such protons should create bubbles of enhanced Cosmic Ray density up to about 13 pc from the recurrent novae

Proton acceleration in thermonuclear nova explosions revealed by gamma rays

Classical novae are cataclysmic binary star systems in which the matter of a companion star is accreted on a white dwarf1,2. Accumulation of hydrogen in a layer eventually causes a thermonuclear explosion on the surface of the white dwarf3, brightening the white dwarf to ~105 solar luminosities and triggering ejection of the accumulated matter. Novae provide the extreme conditions required to accelerate particles, electrons or protons, to high energies. Here we present the detection of gamma rays by the MAGIC telescopes from the 2021 outburst of RS Ophiuchi, a recurrent nova with a red giant companion, which allowed us to accurately characterize the emission from a nova in the 60 GeV to 250 GeV energy range. The theoretical interpretation of the combined Fermi LAT and MAGIC data suggests that protons are accelerated to hundreds of gigaelectronvolts in the nova shock. Such protons should create bubbles of enhanced cosmic ray density, of the order of 10 pc, from the recurrent novae

Gamma rays reveal proton acceleration in thermonuclear novae explosions

Classical novae are cataclysmic binary star systems in which the matter of a companion star is accreted on a white dwarf (WD). Accumulation of the matter in a layer eventually causes a thermonuclear explosion on the surface of the WD, brightening the WD to ~ 10 5 solar luminosities and triggering ejection of the accumulated matter. They provide extreme conditions required to accelerate particles, electrons or protons, to high energies. Here we present the detection of gamma rays by the MAGIC telescopes from the 2021 outburst of RS Ophiuchi (RS Oph), a recurrent symbiotic nova, that allowed us, for the first time, to accurately characterize the emission from a nova in the 60 GeV to 250 GeV energy range. The theoretical interpretation of the combined Fermi -LAT and MAGIC data suggests that protons are accelerated to hundreds of GeV in the nova shock. Such protons should create bubbles of enhanced Cosmic Ray density up to about 13 pc from the recurrent novae

Author Correction: Proton acceleration in thermonuclear nova explosions revealed by gamma rays (Nature Astronomy, (2022), 6, 6, (689-697), 10.1038/s41550-022-01640-z)

In the version of this article initially published, there was an error in the scale described in the right-hand y-axis label of Fig. 1. Flux density (Jy), now presented on a scale from “1, 10, 102”, was originally shown as “10, 102”. The image has been corrected in the HTML and PDF versions of the article. Further, the Source Data for Fig. 1 have now been replaced online