ORCID Profile
0000-0003-4868-0634
Current Organisations
École Polytechnique Fédérale de Lausanne
,
Hospital Universitario Infanta Sofía
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Publisher: American Society for Microbiology
Date: 24-10-2023
Abstract: Multiple respiratory viruses, including influenza A virus (IAV), can be transmitted via expiratory aerosol particles, and aerosol pH was recently identified as a major factor influencing airborne virus infectivity. Indoors, small exhaled aerosols undergo rapid acidification to pH ~4. IAV is known to be sensitive to mildly acidic conditions encountered within host endosomes however, it is unknown whether the same mechanisms could mediate viral inactivation within the more acidic aerosol micro-environment. Here, we identified that transient exposure to pH 4 caused IAV inactivation by a two-stage process, with an initial sharp decline in infectious titers mainly attributed to premature attainment of the post-fusion conformation of viral protein haemagglutinin (HA). Protein changes were observed by hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS) as early as 10 s post-exposure to acidic conditions. Our HDX-MS data are in agreement with other more labor-intensive structural analysis techniques, such as X-ray crystallography, highlighting the ease and usefulness of whole-virus HDX-MS for multiplexed protein analyses, even within enveloped viruses such as IAV. Additionally, virion integrity was partially but irreversibly affected by acidic conditions, with a progressive unfolding of the internal matrix protein 1 (M1) that aligned with a more gradual decline in viral infectivity with time. In contrast, no acid-mediated changes to the genome or lipid envelope were detected. Improved understanding of respiratory virus fate within exhaled aerosols constitutes a global public health priority, and information gained here could aid the development of novel strategies to control the airborne persistence of seasonal and/or pandemic influenza in the future. It is well established that COVID-19, influenza, and many other respiratory diseases can be transmitted by the inhalation of aerosolized viruses. Many studies have shown that the survival time of these airborne viruses is limited, but it remains an open question as to what drives their infectivity loss. Here, we address this question for influenza A virus by investigating structural protein changes incurred by the virus under conditions relevant to respiratory aerosol particles. From prior work, we know that expelled aerosols can become highly acidic due to equilibration with indoor room air, and our results indicate that two viral proteins are affected by these acidic conditions at multiple sites, leading to virus inactivation. Our findings suggest that the development of air treatments to quicken the speed of aerosol acidification would be a major strategy to control infectious bioburdens in the air.
Publisher: Oxford University Press (OUP)
Date: 11-2021
Abstract: There is little evidence around the potentially protective role of previous Bacillus Calmette-Guerin (BCG) vaccination on postoperative mortality in patients with perioperative SARS-CoV-2 vaccination. Prior BCG vaccination did not protect SARS-CoV-2 infected patients against postoperative pulmonary complications and 30-day mortality.
Publisher: Elsevier BV
Date: 08-2021
Publisher: Wiley
Date: 24-08-2021
DOI: 10.1111/ANAE.15563
Abstract: SARS‐CoV‐2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri‐operative or prior SARS‐CoV‐2 were at further increased risk of venous thromboembolism. We conducted a planned sub‐study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS‐CoV‐2 diagnosis was defined as peri‐operative (7 days before to 30 days after surgery) recent (1–6 weeks before surgery) previous (≥7 weeks before surgery) or none. Information on prophylaxis regimens or pre‐operative anti‐coagulation for baseline comorbidities was not available. Postoperative venous thromboembolism rate was 0.5% (666/123,591) in patients without SARS‐CoV‐2 2.2% (50/2317) in patients with peri‐operative SARS‐CoV‐2 1.6% (15/953) in patients with recent SARS‐CoV‐2 and 1.0% (11/1148) in patients with previous SARS‐CoV‐2. After adjustment for confounding factors, patients with peri‐operative (adjusted odds ratio 1.5 (95%CI 1.1–2.0)) and recent SARS‐CoV‐2 (1.9 (95%CI 1.2–3.3)) remained at higher risk of venous thromboembolism, with a borderline finding in previous SARS‐CoV‐2 (1.7 (95%CI 0.9–3.0)). Overall, venous thromboembolism was independently associated with 30‐day mortality (5.4 (95%CI 4.3–6.7)). In patients with SARS‐CoV‐2, mortality without venous thromboembolism was 7.4% (319/4342) and with venous thromboembolism was 40.8% (31/76). Patients undergoing surgery with peri‐operative or recent SARS‐CoV‐2 appear to be at increased risk of postoperative venous thromboembolism compared with patients with no history of SARS‐CoV‐2 infection. Optimal venous thromboembolism prophylaxis and treatment are unknown in this cohort of patients, and these data should be interpreted accordingly.
Publisher: Oxford University Press (OUP)
Date: 25-09-2020
DOI: 10.1002/BJS.12050
Publisher: Proceedings of the National Academy of Sciences
Date: 25-09-2017
Abstract: Our experiments provide the analysis of lipid metabolite circadian oscillations in a cellular system synchronized in vitro, suggesting cell-autonomous diurnal changes in lipid profiles independent of feeding. Moreover, our work represents a comprehensive comparison between the lipid composition of human skeletal muscle derived from sedentary healthy adults, receiving hourly isocaloric solutions, and human primary skeletal myotubes cultured in vitro. A substantial number of lipid metabolites, in particular membrane lipids, exhibited oscillatory patterns in muscle tissue and in myotube cells, where they were blunted upon cell-autonomous clock disruption. As lipid oscillations in skeletal muscle membrane lipids may impact on insulin signaling and on the development of insulin resistance, studying the temporal lipid composition of human muscle is therefore of utmost importance.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 15-04-2022
Abstract: Human cells produce thousands of lipids that change during cell differentiation and can vary across in idual cells of the same type. However, we are only starting to characterize the function of these cell-to-cell differences in lipid composition. Here, we measured the lipidomes and transcriptomes of in idual human dermal fibroblasts by coupling high-resolution mass spectrometry imaging with single-cell transcriptomics. We found that the cell-to-cell variations of specific lipid metabolic pathways contribute to the establishment of cell states involved in the organization of skin architecture. Sphingolipid composition is shown to define fibroblast subpopulations, with sphingolipid metabolic rewiring driving cell-state transitions. Therefore, cell-to-cell lipid heterogeneity affects the determination of cell states, adding a new regulatory component to the self-organization of multicellular systems.
Publisher: Wiley
Date: 17-12-2020
DOI: 10.1111/CODI.15431
Abstract: This study aimed to describe the change in surgical practice and the impact of SARS‐CoV‐2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS‐CoV‐2 pandemic. This was an international cohort study of patients undergoing elective resection of colon or rectal cancer without preoperative suspicion of SARS‐CoV‐2. Centres entered data from their first recorded case of COVID‐19 until 19 April 2020. The primary outcome was 30‐day mortality. Secondary outcomes included anastomotic leak, postoperative SARS‐CoV‐2 and a comparison with prepandemic European Society of Coloproctology cohort data. From 2073 patients in 40 countries, 1.3% (27/2073) had a defunctioning stoma and 3.0% (63/2073) had an end stoma instead of an anastomosis only. Thirty‐day mortality was 1.8% (38/2073), the incidence of postoperative SARS‐CoV‐2 was 3.8% (78/2073) and the anastomotic leak rate was 4.9% (86/1738). Mortality was lowest in patients without a leak or SARS‐CoV‐2 (14/1601, 0.9%) and highest in patients with both a leak and SARS‐CoV‐2 (5/13, 38.5%). Mortality was independently associated with anastomotic leak (adjusted odds ratio 6.01, 95% confidence interval 2.58–14.06), postoperative SARS‐CoV‐2 (16.90, 7.86–36.38), male sex (2.46, 1.01–5.93), age years (2.87, 1.32–6.20) and advanced cancer stage (3.43, 1.16–10.21). Compared with prepandemic data, there were fewer anastomotic leaks (4.9% versus 7.7%) and an overall shorter length of stay (6 versus 7 days) but higher mortality (1.7% versus 1.1%). Surgeons need to further mitigate against both SARS‐CoV‐2 and anastomotic leak when offering surgery during current and future COVID‐19 waves based on patient, operative and organizational risks.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 2021
DOI: 10.1200/JCO.20.01933
Abstract: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9% adjusted odds ratio [aOR], 0.62 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6% aOR, 0.53 95% CI, 0.36 to 0.76). Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.
Publisher: Oxford University Press (OUP)
Date: 24-03-2021
DOI: 10.1093/BJS/ZNAB101
Abstract: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18–49, 50–69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351 best case 196, worst case 816) or non-cancer surgery (733 best case 407, worst case 1664). Both exceeded the NNV in the general population (1840 best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.
Publisher: Elsevier BV
Date: 11-2021
Publisher: Wiley
Date: 24-04-2022
DOI: 10.1111/CODI.16117
Abstract: The SARS‐CoV‐2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non‐delayed surgery. This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January–April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90–1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69–1.27, P = 0.672). Longer delays were not associated with poorer outcomes. One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID‐19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long‐term survival attributable to delays is likely to be due to micro‐metastatic disease.
Location: Spain
No related grants have been discovered for Angel Cuadrado-García.