Pneumonic versus Nonpneumonic Exacerbations of Chronic Obstructive Pulmonary Disease.

Patients with chronic obstructive pulmonary disease (COPD) often suffer acute exacerbations (AECOPD) and community-acquired pneumonia (CAP), named nonpneumonic and pneumonic exacerbations of COPD, respectively. Abnormal host defense mechanisms may play a role in the specificity of the systemic inflammatory response. Given the association of this aspect to some biomarkers at admission (e.g., C-reactive protein), it can be used to help to discriminate AECOPD and CAP, especially in cases with doubtful infiltrates and advanced lung impairment. Fever, sputum purulence, chills, and pleuritic pain are typical clinical features of CAP in a patient with COPD, whereas isolated dyspnea at admission has been reported to predict AECOPD. Although CAP may have a worse outcome in terms of mortality (in hospital and short term), length of hospitalization, and early readmission rates, this has only been confirmed in a few prospective studies. There is a lack of methodologically sound research confirming the impact of severe AECOPD and COPD + CAP. Here, we review studies reporting head-to-head comparisons between AECOPD and CAP + COPD in hospitalized patients. We focus on the epidemiology, risk factors, systemic inflammatory response, clinical and microbiological characteristics, outcomes, and treatment approaches. Finally, we briefly discuss some proposals on how we should orient research in the future

Magnetothermal Conductivity of Highly Oriented Pyrolytic Graphite in the Quantum Limit

We report on the magnetic field (0T$\le B \le 9$T) dependence of the longitudinal thermal conductivity $\kappa(T,B)$ of highly oriented pyrolytic graphite in the temperature range 5 K $\le T\le$ 20 K for fields parallel to the $c-$axis. We show that $\kappa(T,B)$ shows large oscillations in the high-field region (B > 2 T) where clear signs of the Quantum-Hall effect are observed in the Hall resistance. With the measured longitudinal electrical resistivity we show that the Wiedemann-Franz law is violated in the high-field regime.Comment: 4 Figures, to be published in Physical Review B (2003

Risk and Prognostic Factors in Very Old Patients with Sepsis Secondary to Community-Acquired Pneumonia

Background: Little is known about risk and prognostic factors in very old patients developing sepsis secondary to community-acquired pneumonia (CAP). Methods: We conducted a retrospective observational study of data prospectively collected at the Hospital Clinic of Barcelona over a 13-year period. Consecutive patients hospitalized with CAP were included if they were very old (≥80 years) and divided into those with and without sepsis for comparison. Sepsis was diagnosed based on the Sepsis-3 criteria. The main clinical outcome was 30-day mortality. Results: Among the 4219 patients hospitalized with CAP during the study period, 1238 (29%) were very old. The prevalence of sepsis in this age group was 71%. Male sex, chronic renal disease, and diabetes mellitus were independent risk factors for sepsis, while antibiotic therapy before admission was independently associated with a lower risk of sepsis. Thirty-day and intensive care unit (ICU) mortality did not differ between patients with and without sepsis. In CAP-sepsis group, chronic renal disease and neurological disease were independent risk factors for 30-day mortality. Conclusion: In very old patients hospitalized with CAP, in-hospital and 1-year mortality rates were increased if they developed sepsis. Antibiotic therapy before hospital admission was associated with a lower risk of sepsis

Synergistic activation of AMPK prevents from polyglutamine-inducedtoxicity inCaenorhabditis elegans

11 páginas, 4 figuras. Supplementary material related to this article can be found, in the online version, at doi: https://doi.org/10.1016/j.phrs.2020.105105.Expression of abnormally long polyglutamine (polyQ) tracks is the source of a range of dominant neurodegenerative diseases, such as Huntington disease. Currently, there is no treatment for this devastating disease, although some chemicals, e.g., metformin, have been proposed as therapeutic solutions. In this work, we show that metformin, together with salicylate, can synergistically reduce the number of aggregates produced after polyQ expression in Caenorhabditis elegans. Moreover, we demonstrate that incubation polyQ-stressed worms with low doses of both chemicals restores neuronal functionality. Both substances are pleitotropic and may activate a range of different targets. However, we demonstrate in this report that the beneficial effect induced by the combination of these drugs depends entirely on the catalytic action of AMPK, since loss of function mutants of aak-2/AMPKα2 do not respond to the treatment. To further investigate the mechanism of the synergetic activity of metformin/salicylate, we used CRISPR to generate mutant alleles of the scaffolding subunit of AMPK, aakb-1/AMPKβ1. In addition, we used an RNAi strategy to silence the expression of the second AMPKβ subunit in worms, namely aakb-2/AMPKβ2. In this work, we demonstrated that both regulatory subunits of AMPK are modulators of protein homeostasis. Interestingly, only aakb-2/AMPKβ2 is required for the synergistic action of metformin/salicylate to reduce polyQ aggregation. Finally, we showed that autophagy acts downstream of metformin/salicylate-related AMPK activation to promote healthy protein homeostasis in worms.We thank the CGC, funded by the NIH Office of ResearchInfrastructure Programs (P40 OD010440), for worm strains. [...] RPVMis aMiguel Servet type IIresearcher (CPII16/00004) funded by Institutode Salud Carlos III (ISCIII, Madrid, Spain). Grants from the ISCIII wereused to perform this work (PI14/00949 and PI17/00011). All grantsfrom ISCIII are co-financed by the European Development RegionalFund”A way to achieve Europe”(ERDF). JBY holds a grant from theGeneralitat Valenciana and the European Social Fund (ACIF/2019/249). Some equipment used in this work has been funded in partnershipbetween the Generalitat Valenciana (Conselleria de Sanitat I SalutPública, Valencian Community, Spain) and European Funds (ERDF/FSE), through the call "Improvement of research infrastructures for rarediseases”CV FEDER 2014-2020. This work has been partially supportedby a grant from the Fundació Telemarató de la TV3 (Reference 559),which covered the work of MDS. The funds from the ISCIII are partiallysupported by the European Regional Development Fund. RPVM is also aMarie Curie fellow (CIG322034, EU). This work has been partiallysupported by a grant from the CIBERER (ACCI2016), a grant from theFundación Ramón Areces (CIVP19S8119) and anAyuda Miguel Gilgrantto RPVM (VII Convocatoria Ayudas a la Investigación MHER, 2019Peer reviewe

Prognostic implications of comorbidity patterns in critically ill COVID-19 patients: A multicenter, observational study

Background: The clinical heterogeneity of COVID-19 suggests the existence of different phenotypes with prognostic implications. We aimed to analyze comorbidity patterns in critically ill COVID-19 patients and assess their impact on in-hospital outcomes, response to treatment and sequelae. Methods: Multicenter prospective/retrospective observational study in intensive care units of 55 Spanish hospitals. 5866 PCR-confirmed COVID-19 patients had comorbidities recorded at hospital admission; clinical and biological parameters, in-hospital procedures and complications throughout the stay; and, clinical complications, persistent symptoms and sequelae at 3 and 6 months. Findings: Latent class analysis identified 3 phenotypes using training and test subcohorts: low-morbidity (n=3385; 58%), younger and with few comorbidities; high-morbidity (n=2074; 35%), with high comorbid burden; and renal-morbidity (n=407; 7%), with chronic kidney disease (CKD), high comorbidity burden and the worst oxygenation profile. Renal-morbidity and high-morbidity had more in-hospital complications and higher mortality risk than low-morbidity (adjusted HR (95% CI): 1.57 (1.34-1.84) and 1.16 (1.05-1.28), respectively). Corticosteroids, but not tocilizumab, were associated with lower mortality risk (HR (95% CI) 0.76 (0.63-0.93)), especially in renal-morbidity and high-morbidity. Renal-morbidity and high-morbidity showed the worst lung function throughout the follow-up, with renal-morbidity having the highest risk of infectious complications (6%), emergency visits (29%) or hospital readmissions (14%) at 6 months (p<0.01). Interpretation: Comorbidity-based phenotypes were identified and associated with different expression of in-hospital complications, mortality, treatment response, and sequelae, with CKD playing a major role. This could help clinicians in day-to-day decision making including the management of post-discharge COVID-19 sequelae.Financial support was provided by Instituto de Salud Carlos III (CIBERESUCICOVID, COV20/00110), co-funded by Fondo Europeo de Desarrollo Regional (FEDER), “Una manera de hacer Europa”, Centro de Investigación Biomédica en Red − Enfermedades Respiratorias (CIBERES) and Donation Program “estar preparados”, UNESPA, Madrid, Spain. JdB acknowledges receiving financial support from Instituto de Salud Carlos III (ISCIII; Miguel Servet 2019: CP19/00108), cofunded by the European Social Fund (ESF), “Investing in your future”. DdGC acknowledges receiving financial support from Instituto de Salud Carlos III (ISCIII; Miguel Servet 2019: CP20/00041), co-funded by the European Social Fund (ESF), “Investing in your future”. AC acknowledges receiving financial support from Instituto de Salud Carlos III (ISCIII; Sara Borrell 2021: CD21/00087).Peer ReviewedArticle signat per 71 autors/es: Iván D. Benítez (a,b,1), Jordi de Batlle (a,b,1), Gerard Torres (a,b), Jessica Gonzáalez (a,b), David de Gonzalo-Calvo (a,b), Adriano D.S. Targa (a,b), Clara Gort-Paniello (a,b), Anna Moncusí-Moix (a,b), Adrián Ceccato (b,c), Laia Fernández-Barat (b,d), Ricard Ferrer (b,e), Dario Garcia-Gasulla (f), Rosario Menéndez (b,g), Anna Motos (b,d), Oscar Peñuelas (b,h), Jordi Riera (b,e), Jesús F. Bermejo-Martin (b,i), Yhivian Peñasco (j), Pilar Ricart (k), María Cruz Martin Delgado(l), Luciano Aguilera(m), Alejandro Rodríguez(n), Maria Victoria Boado Varela (o), Fernando Suarez-Sipmann (p), Juan Carlos Pozo-Laderas (q), Jordi Solé-Violan (r), Maite Nieto (s), Mariana Andrea Novo (t), José Barberán (u), Rosario Amaya Villar (v), José Garnacho-Montero (w), Jose Luis García-Garmendia (x), José M. Gómez (y), José Ángel Lorente (b,h), Aaron Blandino Ortiz (z), Luis Tamayo Lomas (aa), Esther López-Ramos (ab), Alejandro Úbeda (ac), Mercedes Catalán-González (ad), Angel Sánchez-Miralles (ae), Ignacio Martínez Varela (af), Ruth Noemí Jorge García (ag), Nieves Franco (ah), Víctor D. Gumucio-Sanguino (ai), Arturo Huerta Garcia (aj), Elena Bustamante-Munguira (ak), Luis Jorge Valdivia (al), Jesús Caballero (am), Elena Gallego (an), Amalia Martínez de la Gándara (ao), Álvaro Castellanos-Ortega (ap), Josep Trenado (aq), Judith Marin-Corral (ar), Guillermo M Albaiceta (b,as), Maria del Carmen de la Torre (at), Ana Loza-Vázquez (au), Pablo Vidal (av), Juan Lopez Messa (aw), Jose M. Añon (b,ax), Cristina Carbajales Pérez (ay), Victor Sagredo (az), Neus Bofill (ba), Nieves Carbonell (bb), Lorenzo Socias(bc), Carme Barberá (bd), Angel Estella (be), Manuel Valledor Mendez (bf), Emili Diaz (bg), Ana López Lago (bh), Antoni Torres (b,d) and Ferran Barbé (a,b*), on behalf of the CIBERESUCICOVID Project (COV20/00110, ISCIII)2 // (a) Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain; (b) CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain; (c) Critical Care Center, ParcTaulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Sabadell, Spain; (d) Department of Pneumology, Hospital Clinic of Barcelona; August Pi i Sunyer Biomedical Research Institute−IDIBAPS, University of Barcelona, Barcelona, Spain; (e) Intensive Care Department, Vall d’Hebron Hospital Universitari. SODIR Research Group, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain; (f) Barcelona Supercomputing Center (BSC), Barcelona, Spain; (g) Pulmonology Service, University and Polytechnic Hospital La Fe, Valencia, Spain; (h) Hospital Universitario de Getafe, Madrid, Spain; Universidad Europea, Madrid, Spain; (i) Hospital Universitario Río Hortega de Valladolid, Valladolid, Spain; Group for Biomedical Research in Sepsis (BioSepsis), Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain; (j) Servicio de Medicina Intensiva, Hospital Universitario Marqués de Valdecilla, Santander, Spain; (k) Servei de Medicina Intensiva, Hospital Universitari Germans Trias, Badalona, Spain; (l) Hospital Universitario Torrejón-Universidad Francisco de Vitoria, Madrid, Spain; (m) Servicio de Anestesiología y Reanimación, Hospital Universitario Basurto, Bilbao, Spain; (n) Critical Care Department, Hospital Joan XXIII, Tarragona, Spain; (o) Servicio de Medicina Intensiva, Hospital de Cruces, Baracaldo, Vizcaya, Spain; (p) Intensive Care Unit, Hospital Universitario La Princesa, Madrid, Spain; (q) UGC-Medicina Intensiva, Hospital Universitario Reina Sofia, Instituto Maimonides IMIBIC, Córdoba, Spain; (r) Critical Care Department, Hospital Dr. Negrín Gran Canaria, Las Palmas, Gran Canaria, Spain. Universidad Fernando Pessoa, Canarias, Spain; (s) Hospital Universitario de Segovia, Segovia, Spain; (t) Servei de Medicina Intensiva, Hospital Universitari Son Espases, Palma de Mallorca, Illes Balears, Spain; (u) Hospital Universitario HM Montepríncipe, Universidad San Pablo-CEU, Madrid, Spain; vIntensive Care Clinical Unit, Hospital Universitario Virgen de Rocío, Sevilla, Spain; (w) Intensive Care Clinical Unit, Hospital Universitario Virgen Macarena, Seville, Spain; (x) Intensive Care Unit, Hospital San Juan de Dios del Aljarafe, Bormujos, Sevilla, Spain; (y) Hospital General Universitario Gregorio Marañon, Madrid, Spain; (z) Servicio de Medicina Intensiva, Hospital Universitario Ramón y Cajal, Madrid, Spain; (aa) Critical Care Department, Hospital Universitario Río Hortega de Valladolid, Valladolid, Spain; (ab) Servicio de Medicina Intensiva, Hospital Universitario Príncipe de Asturias, Madrid, Spain; (ac) Servicio de Medicina Intensiva, Hospital Punta de Europa, Algeciras, Spain; (ad) Department of Intensive Care Medicine, Hospital Universitario 12 de Octubre, Madrid, Spain; (ae) Hospital de Sant Joan d’Alacant, Alacant, Spain; (af) Critical Care Department, Hospital Universitario Lucus Augusti, Lugo, Spain; (ag) Intensive Care Department, Hospital Nuestra Señora de Gracia, Zaragoza, Spain; (ah) Hospital Universitario de Móstoles, Madrid, Spain; (ai) Department of Intensive Care. Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain. Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; (aj) Pulmonary and Critical Care Division; Emergency Department, Clínica Sagrada Família, Barcelona, Spain; (ak) Department of Intensive Care Medicine, Hospital Clínico Universitario Valladolid, Valladolid, Spain; (al) Hospital Universitario de León, León, Spain; (am) Critical Care Department, Hospital Universitari Arnau de Vilanova; IRBLleida, Lleida, Spain; (an) Unidad de Cuidados Intensivos, Hospital Universitario San Pedro de Alcántara, Cáceres, Spain; (ao) Department of Intensive Medicine, Hospital Universitario Infanta Leonor, Madrid, Spain; (ap) Servicio de medicina intensiva. Hospital Universitario y Politécnico La Fe, Valencia, Spain; (aq) Servicio de Medicina Intensiva, Hospital Universitario Mútua de Terrassa, Terrassa, Barcelona, Spain; (ar) Critical Care Department, Hospital del Mar-IMIM, Barcelona, Spain; (as) Departamento de Biología Funcional. Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo; Instituto de Investigación Sanitaria del Principado de Asturias, Hospital Central de Asturias, Oviedo, Spain; (at) Hospital de Mataró de Barcelona, Spain; (au) Unidad de Medicina Intensiva, Hospital Universitario Virgen de Valme, Sevilla, Spain; (av) Complexo Hospitalario Universitario de Ourense, Ourense, Spain; (aw) Complejo Asistencial Universitario de Palencia, Palencia, Spain; (ax) Servicio de Medicina Intensiva. Hospital Universitario La Paz, IdiPAZ, Madrid, Spain; (ay) Intensive Care Unit, Hospital Álvaro Cunqueiro, Vigo, Spain; (az) Hospital Universitario de Salamanca, Salamanca, Spain; (ba) Department of Physical Medicine and Rehabilitation, Hospital Verge de la Cinta, Tortosa, Tarragona, Spain; (bb) Intensive Care Unit, Hospital Clínico y Universitario de Valencia, Valencia, Spain; (bc) Intensive Care Unit, Hospital Son Llàtzer, Palma de Mallorca, Illes Balears, Spain; (bd) Hospital Santa Maria; IRBLleida, Lleida, Spain; (be) Intensive Care Unit, University Hospital of Jerez. Medicine Department University of Cadiz. INiBICA, Spain; (bf) Hospital Universitario San Agustín, Asturias, Spain; (bg) Department of Medicine, Universitat Autónoma de Barcelona (UAB); Critical Care Department, Corporació Sanitària Parc Taulí, Sabadell, Barcelona, Spain; (bh) Department of Intensive care Medicine, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, SpainPostprint (published version

Impact of time to intubation on mortality and pulmonary sequelae in critically ill patients with COVID-19: a prospective cohort study

We evaluated whether the time between first respiratory support and intubation of patients receiving invasive mechanical ventilation (IMV) due to COVID-19 was associated with mortality or pulmonary sequelae. Materials and methods: Prospective cohort of critical COVID-19 patients on IMV. Patients were classified as early intubation if they were intubated within the first 48 h from the first respiratory support or delayed intubation if they were intubated later. Surviving patients were evaluated after hospital discharge. Results: We included 205 patients (140 with early IMV and 65 with delayed IMV). The median [p25;p75] age was 63 [56.0; 70.0] years, and 74.1% were male. The survival analysis showed a significant increase in the risk of mortality in the delayed group with an adjusted hazard ratio (HR) of 2.45 (95% CI 1.29–4.65). The continuous predictor time to IMV showed a nonlinear association with the risk of in-hospital mortality. A multivariate mortality model showed that delay of IMV was a factor associated with mortality (HR of 2.40; 95% CI 1.42–4.1). During follow-up, patients in the delayed group showed a worse DLCO (mean difference of -¿10.77 (95% CI -¿18.40 to -¿3.15), with a greater number of affected lobes (+¿1.51 [95% CI 0.89–2.13]) and a greater TSS (+¿4.35 [95% CI 2.41–6.27]) in the chest CT scan. Conclusions: Among critically ill patients with COVID-19 who required IMV, the delay in intubation from the first respiratory support was associated with an increase in hospital mortality and worse pulmonary sequelae during follow-up.Postprint (published version

Cerebrospinal fluid total prion protein in the spectrum of prion diseases

Cerebrospinal fluid (CSF) total prion protein (t-PrP) is decreased in sporadic Creutzfeldt-Jakob disease (sCJD). However, data on the comparative signatures of t-PrP across the spectrum of prion diseases, longitudinal changes during disease progression, and levels in pre-clinical cases are scarce. T-PrP was quantified in neurological diseases (ND, n = 147) and in prion diseases from different aetiologies including sporadic (sCJD, n = 193), iatrogenic (iCJD, n = 12) and genetic (n = 209) forms. T-PrP was also measured in serial lumbar punctures obtained from sCJD cases at different symptomatic disease stages, and in asymptomatic prion protein gene (PRNP) mutation carriers. Compared to ND, t-PrP concentrations were significantly decreased in sCJD, iCJD and in genetic prion diseases associated with the three most common mutations E200K, V210I (associated with genetic CJD) and D178N-129M (associated with fatal familial insomnia). In contrast, t-PrP concentrations in P102L mutants (associated with the Gerstmann-Sträussler-Scheinker syndrome) remained unaltered. In serial lumbar punctures obtained at different disease stages of sCJD patients, t-PrP concentrations inversely correlated with disease progression. Decreased mean t-PrP values were detected in asymptomatic D178-129M mutant carriers, but not in E200K and P102L carriers. The presence of low CSF t-PrP is common to all types of prion diseases regardless of their aetiology albeit with mutation-specific exceptions in a minority of genetic cases. In some genetic prion disease, decreased levels are already detected at pre-clinical stages and diminish in parallel with disease progression. Our data indicate that CSF t-PrP concentrations may have a role as a pre-clinical or early symptomatic diagnostic biomarker in prion diseases as well as in the evaluation of therapeutic interventions

Effect of water and straw management practices on methane emissions from rice fields: A review through a meta-analysis

[EN] Rice fields contribute substantially to global warming of the atmosphere through emission of methane (CH4). This article reviews the state of the art of factors affecting CH4 emissions in rice fields, focusing on soil organic matter content and water management practices. A quantitative relationship between these factors was established through a meta-analysis based on a literature survey. This relationship can be useful to update emission factors used to estimate CH4 in the National Emission Inventories. Methane emissions in rice fields can be as much as 90% higher in continuously flooded rice fields compared with other water management practices, independent from straw addition. Water management systems that involve absence of flooding in total or for part of the growing period such as midseason drainages, intermittent flooding, and percolation control, can reduce CH4 emissions substantially. Moreover, CH4 emissions increase with the amount of straw added up to 7.7 t/ha for continuously flooded soils and up to 5.1 t/ha for other water regimes. Above these levels, no further increase is produced with further addition of straw. With regard to rice straw management mitigation strategies, recommended practices are composting rice straw, straw burning under controlled conditions, recollecting rice straw for biochar production, generation of energy, to be used as a substrate, or to obtain other byproducts with added value. This review improves the understanding of the relationship between straw application rate, water regimes, and CH4 emissions from rice fields to date. This relationship can help to select the most appropriate management practices to improve current mitigation strategies to reduce atmospheric CH4. © 2012 Mary Ann Liebert, Inc.This study was financially supported by Fundacio´n Agroalimed from the Consellerı´a de Agricultura of Valencia, Spain and the Vicerrectorado de Investigacio´n of the UPV (Programa de Apoyo a la Investigacio´n y Desarrollo, PAID06-11 Program, Project No. 1950).Sanchís Jiménez, EM.; Ferrer Roglán, M.; Torres, AG.; Cambra López, M.; Calvet Sanz, S. (2012). Effect of water and straw management practices on methane emissions from rice fields: A review through a meta-analysis. Environmental Engineering Science. 29(12):1053-1062. https://doi.org/10.1089/ees.2012.0006S10531062291

The clustering of ultra-high energy cosmic rays and their sources

The sky distribution of cosmic rays with energies above the 'GZK cutoff' holds important clues to their origin. The AGASA data, although consistent with isotropy, shows evidence for small-angle clustering, and it has been argued that such clusters are aligned with BL Lacertae objects, implicating these as sources. It has also been suggested that clusters can arise if the cosmic rays come from the decays of very massive relic particles in the Galactic halo, due to the expected clumping of cold dark matter. We examine these claims and show that both are in fact not justified.Comment: 13 pages, 8 figures, version in press at Phys. Rev.