Clinical features and outcomes of tuberculosis in transplant recipients as compared with the general population: a retrospective matched cohort study

AbstractThere are no previous studies comparing tuberculosis in transplant recipients (TRs) with other hosts. We compared the characteristics and outcomes of tuberculosis in TRs and patients from the general population. Twenty-two TRs who developed tuberculosis from 1996 through 2010 at a tertiary hospital were included. Each TR was matched by age, gender and year of diagnosis with four controls selected from among non-TR non-human immunodeficiency virus patients with tuberculosis. TRs (21 patients, 96%) had more factors predisposing to tuberculosis than non-TRs (33, 38%) (p <0.001). Pulmonary tuberculosis was more common in non-TRs (77 (88%) vs. 12 TRs (55%); p 0.001); disseminated tuberculosis was more frequent in TRs (five (23%) vs. four non-TRs (5%); p 0.005). Time from clinical suspicion of tuberculosis to definitive diagnosis was longer in TRs (median of 14 days) than in non-TRs (median of 0 days) (p <0.001), and invasive procedures were more often required (12 (55%) TRs and 15 (17%) non-TRs, respectively; p 0.001). Tuberculosis was diagnosed post-mortem in three TRs (14%) and in no non-TRs (p <0.001). Rates of toxicity associated with antituberculous therapy were 38% in TRs (six patients) and 10% (seven patients) in non-TRs (p 0.014). Tuberculosis-related mortality rates in TRs and non-TRs were 18% and 6%, respectively (p 0.057). The adjusted Cox regression analysis showed that the only predictor of tuberculosis-related mortality was a higher number of organs with tuberculosis involvement (adjusted hazard ratio 8.6; 95% CI 1.2–63). In conclusion, manifestations of tuberculosis in TRs differ from those in normal hosts. Post-transplant tuberculosis resists timely diagnosis, and is associated with a higher risk of death before a diagnosis can be made

Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients with Inflammatory Bowel Disease: Results from the Eneida Registry

Background: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. Methods: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. Results: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn''s disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. Conclusions: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response

Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1

Altres ajuts: This study was sponsored by Janssen.Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52-96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52–96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF

Helium identification with LHCb

The identification of helium nuclei at LHCb is achieved using a method based on measurements of ionisation losses in the silicon sensors and timing measurements in the Outer Tracker drift tubes. The background from photon conversions is reduced using the RICH detectors and an isolation requirement. The method is developed using pp collision data at √(s) = 13 TeV recorded by the LHCb experiment in the years 2016 to 2018, corresponding to an integrated luminosity of 5.5 fb-1. A total of around 105 helium and antihelium candidates are identified with negligible background contamination. The helium identification efficiency is estimated to be approximately 50% with a corresponding background rejection rate of up to O(10^12). These results demonstrate the feasibility of a rich programme of measurements of QCD and astrophysics interest involving light nuclei

Momentum scale calibration of the LHCb spectrometer

For accurate determination of particle masses accurate knowledge of the momentum scale of the detectors is crucial. The procedure used to calibrate the momentum scale of the LHCb spectrometer is described and illustrated using the performance obtained with an integrated luminosity of 1.6 fb-1 collected during 2016 in pp running. The procedure uses large samples of J/ψ → μ + μ - and B+ → J/ψ K + decays and leads to a relative accuracy of 3 × 10-4 on the momentum scale

Curvature-bias corrections using a pseudomass method

Momentum measurements for very high momentum charged particles, such as muons from electroweak vector boson decays, are particularly susceptible to charge-dependent curvature biases that arise from misalignments of tracking detectors. Low momentum charged particles used in alignment procedures have limited sensitivity to coherent displacements of such detectors, and therefore are unable to fully constrain these misalignments to the precision necessary for studies of electroweak physics. Additional approaches are therefore required to understand and correct for these effects. In this paper the curvature biases present at the LHCb detector are studied using the pseudomass method in proton-proton collision data recorded at centre of mass energy √(s)=13 TeV during 2016, 2017 and 2018. The biases are determined using Z→μ + μ - decays in intervals defined by the data-taking period, magnet polarity and muon direction. Correcting for these biases, which are typically at the 10-4 GeV-1 level, improves the Z→μ + μ - mass resolution by roughly 18% and eliminates several pathological trends in the kinematic-dependence of the mean dimuon invariant mass