Software-defined open architecture for front- and backhaul in 5G mobile networks

New software-defined open network concepts are proposed in this paper to enable an efficient implementation of front- and backhaul solutions for future 5G mobile networks. Main requirements for 5G front- and backhaul are derived and then related to the open network architecture enabling multiple operators to share the same physical infrastructure. The value of software-defined networking (SDN) is particularly outlined therefore. For the use of SDN in the fronthaul, CPRI over Ethernet (CoE) is proposed as a new transport protocol. In the backhaul, distributed security can be implemented using SDN where direct links are confined inside the access domain, as opposed to the current centralized security solution including also the transport domain. In this way, low latency can be realized e.g. for machine-type communications. As the benefits for fixed-mobile convergence are evident, SDN should be enabled increasingly in the access domain. © 2014 IEEE

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

COVID-19; Mechanical ventilation; Ventilatory ratioCOVID-19; Respiració assistida; Relació ventilatòriaCOVID-19; Ventilación mecánica; Relación ventilatoriaBackground Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0–171.2] to 180.0 [135.4–227.9] mmHg and the ventilatory ratio from 1.73 [1.33–2.25] to 1.96 [1.61–2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01–1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01–1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93–1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation.Financial support was provided by the Instituto de Salud Carlos III de Madrid (COV20/00110, ISCIII), Fondo Europeo de Desarrollo Regional (FEDER), "Una manera de hacer Europa", and by the Centro de Investigación Biomedica En Red – Enfermedades Respiratorias (CIBERES). DdGC has received financial support from Instituto de Salud Carlos III (Miguel Servet 2020: CP20/00041), co-funded by European Social Fund (ESF)/”Investing in your future”

Autophagy induction halts axonal degeneration in a mouse model of x-adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is a rare neurometabolic disease characterized by the accumulation of very long chain fatty acids (VLCFAs) due to a loss of function of the peroxisomal transporter ABCD1. Here, using in vivo and in vitro models, we demonstrate that autophagic flux was impaired due to elevated mammalian target of rapamycin (mTOR) signaling, which contributed to X-ALD pathogenesis. We also show that excess VLCFAs downregulated autophagy in human fibroblasts. Furthermore, mTOR inhibition by a rapamycin derivative (temsirolimus) restored autophagic flux and inhibited the axonal degenerative process as well as the associated locomotor impairment in the Abcd1 (-) /Abcd2 (-/-) mouse model. This process was mediated through the restoration of proteasome function and redox as well as metabolic homeostasis. These findings provide the first evidence that links impaired autophagy to X-ALD, which may yield a therapy based on autophagy activators for adrenomyeloneuropathy patients

Effects of intubation timing in patients with COVID-19 throughout the four waves of the pandemic: a matched analysis

Background: The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with COVID-19-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior non-invasive respiratory support on outcomes. Methods: This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICU) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of intensive care unit (ICU) admission. Propensity score (PS) matching was used to achieve balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different timepoint (48 h from ICU admission) for early and delayed intubation. Results: Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After PS matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%, p =0.01), ICU mortality (25.7% versus 36.1%, p=0.007) and 90-day mortality (30.9% versus 40.2%, p=0.02) when compared to the early intubation group. Very similar findings were observed when we used a 48-hour timepoint for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth wave, respectively; first versus second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (n=294) who were intubated earlier. The subgroup of patients undergoing NIV (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h. Conclusions: In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received high-flow nasal cannula.Financial support was provided by the Instituto de Salud Carlos III de Madrid (COV20/00110, ISCIII), Fondo Europeo de Desarrollo Regional (FEDER), "Una manera de hacer Europa", and the Centro de Investigación Biomedica En Red – Enfermedades Respiratorias (CIBERES). DdGC has received financial support from the Instituto de Salud Carlos III (Miguel Servet 2020: CP20/00041), co-funded by European Social Fund (ESF)/”Investing in your future”.Peer ReviewedArticle signat per 70 autors/es: Jordi Riera*1,2; Enric Barbeta*2,3,4; Adrián Tormos5; Ricard Mellado-Artigas2,3; Adrián Ceccato6; Anna Motos4; Laia Fernández-Barat4; Ricard Ferrer1; Darío García-Gasulla5; Oscar Peñuelas7; José Ángel Lorente7; Rosario Menéndez8; Oriol Roca1,2; Andrea Palomeque4,9; Carlos Ferrando2,3; Jordi SoléViolán10; Mariana Novo11; María Victoria Boado12; Luis Tamayo13; Ángel Estella14, Cristóbal Galban15; Josep Trenado16; Arturo Huerta17; Ana Loza18; Luciano Aguilera19; José Luís García Garmendia20; Carme Barberà21; Víctor Gumucio22; Lorenzo Socias23; Nieves Franco24; Luis Jorge Valdivia25; Pablo Vidal26; Víctor Sagredo27; Ángela Leonor Ruiz-García28; Ignacio Martínez Varela29; Juan López30; Juan Carlos Pozo31; Maite Nieto32; José M Gómez33; Aaron Blandino34; Manuel Valledor35; Elena Bustamante-Munguira36; Ángel Sánchez-Miralles37; Yhivian Peñasco38; José Barberán39; Alejandro Ubeda40; Rosario Amaya-Villar41; María Cruz Martín42; Ruth Jorge43; Jesús Caballero44; Judith Marin45; José Manuel Añón46; Fernando Suárez Sipmann47; Guillermo Muñiz2,48;Álvaro Castellanos-Ortega49; Berta Adell-Serrano50; Mercedes Catalán51; Amalia Martínez de la Gándara52; Pilar Ricart53; Cristina Carbajales54; Alejandro Rodríguez55; Emili Díaz6; Mari C de la Torre56; Elena Gallego57; Luisa Cantón-Bulnes58; Nieves Carbonell59, Jessica González60, David de Gonzalo-Calvo60, Ferran Barbé60 and Antoni Torres2,4,9 on behalf of the CiberesUCICOVID Consortium. // 1. Critical Care Department, Hospital Universitari Vall d’Hebron; SODIR, Vall d’Hebron Institut de Recerca, Barcelona, Spain. 2. CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain. 3.Surgical Intensive Care Unit, Hospital Clínic de Barcelona, Barcelona, Spain. 4. Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona (UB), Barcelona, Spain. 5. Barcelona Supercomputing Center (BSC), Barcelona, Spain. 6. Critical Care Center, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Sabadell, Spain. Universitat Autonoma de Barcelona (UAB), Spain. 7. Hospital Universitario de Getafe, Universidad Europea, Madrid, Spain. 8. Pneumology Department, Hospital Universitario y Politécnico La Fe/Instituto de Investigación Sanitaria (IIS) La Fe, 46026 Valencia, Spain; Pneumology Department, Hospital Universitario y Politécnico La Fe, Avda, Fernando Abril Martorell 106, 46026 Valencia, Spain. 9.Respiratory Intensive Care Unit, Hospital Clínic de Barcelona, Barcelona, Spain. 10. Critical Care Department, Hospital Dr. Negrín Gran Canaria. Universidad Fernando Pessoa. Las Palmas, Gran Canaria, Spain. 11. Servei de Medicina Intensiva, Hospital Universitari Son Espases, Palma de Mallorca, Illes Balears, Spain. 12. Hospital Universitario de Cruces, Barakaldo, Spain. 13. Critical Care Department, Hospital Universitario Río Hortega de Valladolid, Valladolid, Spain. 14. Departamento Medicina Facultad Medicina Universidad de Cádiz. Hospital Universitario de Jerez, Jerez de la Frontera, Spain. 15. Department of Medicine, CHUS, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain. 16. Servicio de Medicina Intensiva, Hospital Universitario Mútua de Terrassa, Terrassa, Barcelona, Spain. 17. Pulmonary and Critical Care Division; Emergency Department, Clínica Sagrada Família, Barcelona, Spain. 18. Hospital Virgen de Valme, Sevilla, Spain. 19. Hospital de Basurto, Bilbao, Spain. 20. Intensive Care Unit, Hospital San Juan de Dios del Aljarafe, Bormujos, Sevilla, Spain. 21. Hospital Santa Maria; IRBLleida, Lleida, Spain. 22. 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. 23. Intensive Care Unit, Hospital Son Llàtzer, Palma de Mallorca, Illes Balears, Spain. 24. Hospital Universitario de Móstoles, Madrid, Spain. 25. Hospital Universitario de León, León, Spain. 26. Complexo Hospitalario Universitario de Ourense, Ourense, Spain. 27. Hospital Universitario de Salamanca, Salamanca, Spain. 28. Servicio de Microbiología Clínica, Hospital Universitario Príncipe de Asturias – Departamento de Biomedicina y Biotecnología, Universidad de Alcalá de Henares, Madrid, Spain. 29. Critical Care Department, Hospital Universitario Lucus Augusti, Lugo, Spain. 30. Complejo Asistencial Universitario de Palencia, Palencia, Spain. 31. UGC-Medicina Intensiva, Hospital Universitario Reina Sofia, Instituto Maimonides IMIBIC, Córdoba, Spain. 32. Hospital Universitario de Segovia, Segovia, Spain. 33. Hospital General Universitario Gregorio Marañón, Madrid, Spain. 34. Servicio de Medicina Intensiva, Hospital Universitario Ramón y Cajal, Madrid, Spain. 35. Hospital Universitario "San Agustín", Avilés, Spain. 36. Department of Intensive Care Medicine, Hospital Clínico Universitario Valladolid, Valladolid, Spain. 37. Servicio de Medicina Intensiva. Hospital Universitario Sant Joan d´Alacant, Alicante, Spain. 38. Servicio de Medicina Intensiva, Hospital Universitario Marqués de Valdecilla, Santander, Spain. 39. Hospital Universitario HM Montepríncipe, Universidad San Pablo-CEU, Madrid, Spain. 40. Servicio de Medicina Intensiva, Hospital Punta de Europa, Algeciras, Spain. 41. Intensive Care Clinical Unit, Hospital Universitario Virgen de Rocío, Sevilla, Spain. 42. Hospital Universitario Torrejón- Universidad Francisco de Vitoria, Madrid, Spain. 43. Intensive Care Department, Hospital Nuestra Señora de Gracia, Zaragoza, Spain. 44. Critical Care Department, Hospital Universitari Arnau de Vilanova; IRBLleida, Lleida, Spain. 45. Critical Care Department, Hospital del Mar-IMIM, Barcelona, Spain. 46. Hospital Universitario la Paz, Madrid, Spain. 47. Intensive Care Unit, Hospital Universitario La Princesa, Madrid, Spain. 48. 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. 49. Hospital Universitario y Politécnico la Fe, Valencia, Spain. 50. Hospital de Tortosa Verge de la Cinta, Tortosa, Tarragona, Spain. 51. Department of Intensive Care Medicine, Hospital Universitario 12 de Octubre, Madrid, Spain. 52. Hospital Universitario Infanta Leonor, Madrid, Spain. 53. Servei de Medicina Intensiva, Hospital Universitari Germans Trias, Badalona, Spain. 54. Intensive Care Unit, Hospital Álvaro Cunqueiro, Vigo, Spain. 55. Hospital Universitari Joan XXIII de Tarragona, Tarragona, Spain. 56. Hospital de Mataró de Barcelona, Spain. 57. Unidad de Cuidados Intensivos, Hospital Universitario San Pedro de Alcántara, Cáceres, Spain. 58. Unidad de Cuidados Intensivos, Hospital Virgen Macarena, Sevilla, Spain. 59. Intensive Care Unit, Hospital Clínico y Universitario de Valencia, Valencia, Spain. 60. Translational Research in Respiratory Medicine, Respiratory Department, Hospital Universitari Aranu de Vilanova and Santa Maria, IRBLleida, Lleida, Spain.Postprint (published version

Major candidate variables to guide personalised treatment with steroids in critically ill patients with COVID-19: CIBERESUCICOVID study

Purpose: Although there is evidence supporting the benefits of corticosteroids in patients affected with severe coronavirus disease 2019 (COVID-19), there is little information related to their potential benefits or harm in some subgroups of patients admitted to the intensive care unit (ICU) with COVID-19. We aim to investigate to find candidate variables to guide personalized treatment with steroids in critically ill patients with COVID-19. Methods: Multicentre, observational cohort study including consecutive COVID-19 patients admitted to 55 Spanish ICUs. The primary outcome was 90-day mortality. Subsequent analyses in clinically relevant subgroups by age, ICU baseline illness severity, organ damage, laboratory findings and mechanical ventilation were performed. High doses of corticosteroids (≥ 12 mg/day equivalent dexamethasone dose), early administration of corticosteroid treatment (< 7 days since symptom onset) and long term of corticosteroids (≥ 10 days) were also investigated. Results: Between February 2020 and October 2021, 4226 patients were included. Of these, 3592 (85%) patients had received systemic corticosteroids during hospitalisation. In the propensity-adjusted multivariable analysis, the use of corticosteroids was protective for 90-day mortality in the overall population (HR 0.77 [0.65–0.92], p = 0.003) and in-hospital mortality (SHR 0.70 [0.58–0.84], p < 0.001). Significant effect modification was found after adjustment for covariates using propensity score for age (p = 0.001 interaction term), Sequential Organ Failure Assessment (SOFA) score (p = 0.014 interaction term), and mechanical ventilation (p = 0.001 interaction term). We observed a beneficial effect of corticosteroids on 90-day mortality in various patient subgroups, including those patients aged ≥ 60 years; those with higher baseline severity; and those receiving invasive mechanical ventilation at ICU admission. Early administration was associated with a higher risk of 90-day mortality in the overall population (HR 1.32 [1.14–1.53], p < 0.001). Long-term use was associated with a lower risk of 90-day mortality in the overall population (HR 0.71 [0.61–0.82], p < 0.001). No effect was found regarding the dosage of corticosteroids. Moreover, the use of corticosteroids was associated with an increased risk of nosocomial bacterial pneumonia and hyperglycaemia. Conclusion: Corticosteroid in ICU-admitted patients with COVID-19 may be administered based on age, severity, baseline inflammation, and invasive mechanical ventilation. Early administration since symptom onset may prove harmful.15 página

Pulmonary Air Embolism in a Patient with COVID-19 with Extracorporeal Membrane Oxygenation Support

Embòlia aèria pulmonar; COVID-19Embolia aérea pulmonar; COVID-19Pulmonary air embolism; COVID-1

Pulmonary function and radiologic features in survivors of critical COVID-19: a 3-month prospective cohort

© 2021 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/BACKGROUND: More than 20% of hospitalized patients with COVID-19 demonstrate ARDS requiring ICU admission. The long-term respiratory sequelae in such patients remain unclear. RESEARCH QUESTION: What are the major long-term pulmonary sequelae in critical patients who survive COVID-19? STUDY DESIGN AND METHODS: Consecutive patients with COVID-19 requiring ICU admission were recruited and evaluated 3 months after hospitalization discharge. The follow-up comprised symptom and quality of life, anxiety and depression questionnaires, pulmonary function tests, exercise test (6-min walking test [6MWT]), and chest CT imaging. RESULTS: One hundred twenty-five patients admitted to the ICU with ARDS secondary to COVID- 19 were recruited between March and June 2020. At the 3-month follow-up, 62 patients were available for pulmonary evaluation. The most frequent symptoms were dyspnea (46.7%) and cough (34.4%). Eighty-two percent of patients showed a lung diffusing capacity of less than 80%. The median distance in the 6MWT was 400 m (interquartile range, 362-440 m). CT scans showed abnormal results in 70.2% of patients, demonstrating reticular lesions in 49.1% and fibrotic patterns in 21.1%. Patients with more severe alterations on chest CT scan showed worse pulmonary function and presented more degrees of desaturation in the 6MWT. Factors associated with the severity of lung damage on chest CT scan were age and length of invasive mechanical ventilation during the ICU stay. INTERPRETATION: Three months after hospital discharge, pulmonary structural abnormalities and functional impairment are highly prevalent in patients with ARDS secondary to COVID- 19 who required an ICU stay. Pulmonary evaluation should be considered for all critical COVID-19 survivors 3 months after discharge.This study was supported in part by the Instituto de Salud Carlos III [Grant CIBERESUCICOVID, COV20/00110] and was cofunded by European Regional Development Funds, “Una manera de hacer Europa.” D. d. G.-C. has received financial support from the Instituto de Salud Carlos III [Grant Miguel Servet 2020: CP20/00041], co-funded by the European Social Fund “Investing in Your Future.” L. P. acknowledges receiving financial support from the Ministry of Science, Innovation and Universities for the Training of University Lecturers (FPU19 / 03526).Peer ReviewedPostprint (author's final draft

One Year Overview and Follow-Up in a Post-COVID Consultation of Critically Ill Patients

The long-term clinical management and evolution of a cohort of critical COVID-19 survivors have not been described in detail. We report a prospective observational study of COVID-19 patients admitted to the ICU between March and August 2020. The follow-up in a post-COVID consultation comprised symptoms, pulmonary function tests, the 6-minute walking test (6MWT), and chest computed tomography (CT). Additionally, questionnaires to evaluate the prevalence of post-COVID-19 syndrome were administered at 1 year. A total of 181 patients were admitted to the ICU during the study period. They were middle-aged (median [IQR] of 61 [52;67]) and male (66.9%), with a median ICU stay of 9 (5-24.2) days. 20% died in the hospital, and 39 were not able to be included. A cohort of 105 patients initiated the follow-up. At 1 year, 32.2% persisted with respiratory alterations and needed to continue the follow-up. Ten percent still had moderate/severe lung diffusion (DLCO) involvement (<60%), and 53.7% had a fibrotic pattern on CT. Moreover, patients had a mean (SD) number of symptoms of 5.7 ± 4.6, and 61.3% met the criteria for post-COVID syndrome at 1 year. During the follow-up, 46 patients were discharged, and 16 were transferred to other consultations. Other conditions, such as emphysema (21.6%), COPD (8.2%), severe neurocognitive disorders (4.1%), and lung cancer (1%) were identified. A high use of health care resources is observed in the first year. In conclusion, one-third of critically ill COVID-19 patients need to continue follow-up beyond 1 year, due to abnormalities on DLCO, chest CT, or persistent symptoms.This study was supported in part by ISCIII (CIBERESUCICOVID, COV20/00110), co-funded by ERDF, “Una manera de hacer Europa,” donation program “Estar Preparados,” UNESPA, Madrid, Spain and Fundación Soria Melguizo (Madrid, Spain). DG-C had received financial support from Instituto de Salud Carlos III (Miguel Servet 2020: CP20/00041), co-funded by the European Social Fund (ESF)/“Investing in your future.” JB acknowledged receiving financial support from Instituto de Salud Carlos III (ISCIII; Miguel Servet 2019: CP19/00108), co-funded by the European Social Fund (ESF), “Investing in your future.