Improvisation in times of pandemic, a reason for reflection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been one of the most significant health crises worldwide in the last decades. This new pandemic has brought to light the strengths and weaknesses of current health care systems worldwide, even in countries that pride themselves on being at the forefront in terms of clinical, scientific, and technological capacity and development. Crises such as these are also opportunities to reflect and learn. Coronavirus disease 2019 (COVID-19) has provided us with several valuable lessons that involve the whole spectrum of medical practice: human, scientific, technical, and social

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide versus dolutegravir /abacavir/lamivudine in antiretroviral-naïve adults (SYMTRI): a multicenter randomized open-label study (PReEC/RIS-57)

D/C/F/TAF is the reference for combination therapy based on protease inhibitors but has not been compared with regimens containing integrase inhibitors as initial ART. We could not demonstrate D/C/F/TAF noninferiority relative to DTG/ABC/3TC, although both regimens were similarly well tolerated. Background Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) is the reference for combination therapy based on protease inhibitors due to its efficacy, tolerability, and convenience. Head-to-head randomized comparisons between D/C/F/TAF and combination therapy based on integrase inhibitors in antiretroviral-naive patients are lacking. Methods Adult (>18 years old) human immunodeficiency virus-infected antiretroviral-naive patients (HLA-B*5701 negative and hepatitis B virus negative), with viral load (VL) >= 500 c/mL, were centrally randomized to initiate D/C/F/TAF or dolutegravir/abacavir/lamivudine (DTG/3TC/ABC) after stratifying by VL and CD4 count. Clinical and analytical assessments were performed at weeks 0, 4, 12, 24, and 48. The primary endpoint was VL 100 000 copies/mL, and 13% had <200 CD4 cells/mu L. Median weight was 73 kg and median body mass index was 24 kg/m(2). At 48 weeks, 79% (D/C/F/TAF) versus 82% (DTG/3TC/ABC) had VL <50 c/mL (difference, -2.4%; 95% confidence interval [CI], -11.3 to 6.6). Eight percent versus four percent experienced virologic failure but no resistance-associated mutations emerged. Four percent versus six percent had drug discontinuation due to adverse events. In the per-protocol analysis, 94% versus 96% of patients had VL <50 c/mL (difference, -2%; 95% CI, -8.1 to 3.5). There were no differences in CD4 cell count or weight changes. Conclusions We could not demonstrate the noninferiority of D/C/F/TAF relative to DTG/ABC/3TC as initial antiretroviral therapy, although both regimens were similarly well tolerated

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3

ObjectivesCARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.MethodsIn total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC &gt; 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.ResultsIn total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were blaOXA–48 (263/377), blaKPC–3 (62/377), blaVIM–1 (28/377), and blaNDM–1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5).ConclusionThis study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3

Improvisation in times of pandemic, a reason for reflection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been one of the most significant health crises worldwide in the last decades. This new pandemic has brought to light the strengths and weaknesses of current health care systems worldwide, even in countries that pride themselves on being at the forefront in terms of clinical, scientific, and technological capacity and development. Crises such as these are also opportunities to reflect and learn. Coronavirus disease 2019 (COVID-19) has provided us with several valuable lessons that involve the whole spectrum of medical practice: human, scientific, technical, and social

Outcomes by sex following treatment initiation with darunavir/cobicistat in a large Spanish cohort of the CODAR study (GeSIDA 9316)

[Background] Few women have been included in darunavir/cobicistat clinical development studies, and hardly any of them were antiretroviral experienced or treated with anything other than triple-based therapies.[Objectives] Our aim was to increase our knowledge about women living with HIV undergoing darunavir/cobicistat-based regimens.[Methods] A multicentre (21 hospitals), retrospective study including a centrally selected random sample of HIV-1 patients starting a darunavir/cobicistat-based regimen from June 2014 to March 2017 was planned. Baseline characteristics, 24 and 48 week viral load response (<50 copies/mL), CD4+ lymphocyte count increase, time to change darunavir/cobicistat and adverse event occurrence were all compared by sex. The study was approved by each of the 21 ethics committees, and patients signed informed consent.[Results] Out of 761 participants, 193 were women. Similar characteristics were found for both sexes, except that the women had a longer duration of HIV infection (P = 0.001), and were less frequently pre-treated with darunavir/cobicistat in their previous regimen (P = 0.02). The main reason for using a darunavir/cobicistat-based regimen was simplification, without differences by sex, while monotherapy seems to be more frequently prescribed in women than in men (P = 0.067). The main outcomes, HIV viral load response, CD4+ lymphocyte count increase at 24 or 48 weeks, occurrence of adverse events, main reasons for changing and time to the modify darunavir/cobicistat regimen, did not show differences between the sexes.[Conclusions] No sex disparities were found in the main study outcomes. These results support the use of a darunavir/cobicistat-based regimen in long-term pre-treated women. Clinical Trial.gov No. NCT03042390.The CODAR study (Gesida Study no. 9316) was sponsored by SEIMC-GESIDA with support from Janssen. Other contributors were the RD12/0017/0017 project as part of Plan Nacional R + D + I and co-funded by Instituto de Salud Carlos III (ISCIII)-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER).Peer reviewe

Myocardial work index in professional football players: A novel method for assessment of cardiac adaptation

: Background: The global myocardial work index (GWI), a novel, valid, and non-invasive method based on speckle-tracking echocardiography, could provide value for calculating left ventricular (LV) function and energy consumption in athletes. Materials and Methods: We prospectively analyzed a single-center cohort of Spanish First-Division football players who attended a pre-participation screening program from June 2020 to June 2021, compared to a control group. All the individuals underwent an electrocardiogram and echocardiography, including two-dimensional speckle tracking and 4D-echo. The study aimed to evaluate the feasibility of myocardial work in professional football players and its correlations with other echocardiographic parameters. Results: The study population comprised 97 individuals (49 professional players and 48 controls). The mean age was 30.48 ± 7.20 years old. The professional football players had significantly higher values of LVEDV (p < 0.001), LVESV (p < 0.001), LV-mass index (p = 0.011), PWTd (p = 0.023), and EA (p < 0.001) compared with the control group. In addition, the professional players had lower GCW (p = 0.003) and a tendency to show lower GWI values (p < 0.001). These findings could suggest that professional football players have more remodeling and less MW, related to their adaptation to intensive training. Significant differences in GLS (p = 0.01) and GWE (p = 0.04) were observed as a function of the septal thickness of the athletes. Irrespective of the MW variable, the parameters with better correlations across all the populations were SBP, DBP, and GLS. Conclusions: The GWI is a novel index to assess cardiac performance, with less load dependency than strain measurements. Future GWI analyses are warranted to understand myocardial deformation and other pathological differential diagnoses