50 research outputs found
Supernatants from lymphocytes stimulated with Bacillus Calmette-Guerin can modify the antigenicity of tumours and stimulate allogeneic T-cell responses
No full textChapter 12 - Co-solvents and mobile phase additives in HPLC
No full textIn this chapter, a selected number of applications regarding the use of co-solvents and mobile phase additives to improve the quality of RP-HPLC applications are described. The beneficial effects deriving from the presence in the eluent of fluorinated ion-pairing reagents (carboxylic acids, amines, and alcohols), ionic liquids, deep eutectic solvents, chaotropic and kosmotropic agents, and surfactants are discussed with studies retrieved from the literature. All the sections included in the chapter provide evidence about the remarkable impact that some additives and co-solvents can have on both the thermodynamic and the kinetic features of the LC processes, in turn highlighting that the mobile phase components are deeply involved in the overall chromatographic process at multiple levels, even if present at low concentrations
Photoredox catalysis powered by triplet fusion upconversion: arylation of heteroarenes
No full text[EN] In this work, the feasibility of triplet fusion upconversion (TFU, also named triplet-triplet annihilation upconversion) technology for the functionalization (arylation) of furans and thiophenes has been successfully proven. Activation of aryl halides by TFU leads to generation of aryl radical intermediates; trapping of the latter by the corresponding heteroarenes, which act as nucleophiles, affords the final coupling products. Advantages of this photoredox catalytic method include the use of very mild conditions (visible light, standard conditions), employment of commercially available reactants and low-loading metal-free photocatalysts, absence of any sacrificial agent (additive) in the medium and short irradiation times. The involvement of the high energetic delayed fluorescence in the reaction mechanism has been evidenced by quenching studies, whereas the two-photon nature of this photoredox arylation of furans and thiophenes has been manifested by the dependence on the energy source power. Finally, the scaling-up conditions have been gratifyingly afforded by a continuous-flow device.We thank the Generalitat Valenciana (project CIDEGENT/2018/044) and the Spanish Government (project PID2019-105391GB-C22 funded by MCIN/AEI/10.13039/501100011033 and fellowship PRE2020-093783 funded by MCIN/AEI/10.13039/501100011033) for financial support. We also thank Prof. Julia Perez-Prieto for spectroscopy facilities.Castellanos-Soriano, J.; Álvarez-Gutiérrez, D.; Jiménez Molero, MC.; Pérez-Ruiz, R. (2022). Photoredox catalysis powered by triplet fusion upconversion: arylation of heteroarenes. 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Endovascular treatment for acute ischemic stroke
No full textBACKGROUND:
In patients with ischemic stroke, endovascular treatment results in a higher rate of recanalization of the affected cerebral artery than systemic intravenous thrombolytic therapy. However, comparison of the clinical efficacy of the two approaches is needed.
METHODS:
We randomly assigned 362 patients with acute ischemic stroke, within 4.5 hours after onset, to endovascular therapy (intraarterial thrombolysis with recombinant tissue plasminogen activator [t-PA], mechanical clot disruption or retrieval, or a combination of these approaches) or intravenous t-PA. Treatments were to be given as soon as possible after randomization. The primary outcome was survival free of disability (defined as a modified Rankin score of 0 or 1 on a scale of 0 to 6, with 0 indicating no symptoms, 1 no clinically significant disability despite symptoms, and 6 death) at 3 months.
RESULTS:
A total of 181 patients were assigned to receive endovascular therapy, and 181 intravenous t-PA. The median time from stroke onset to the start of treatment was 3.75 hours for endovascular therapy and 2.75 hours for intravenous t-PA (P<0.001). At 3 months, 55 patients in the endovascular-therapy group (30.4%) and 63 in the intravenous t-PA group (34.8%) were alive without disability (odds ratio adjusted for age, sex, stroke severity, and atrial fibrillation status at baseline, 0.71; 95% confidence interval, 0.44 to 1.14; P=0.16). Fatal or nonfatal symptomatic intracranial hemorrhage within 7 days occurred in 6% of the patients in each group, and there were no significant differences between groups in the rates of other serious adverse events or the case fatality rate.
CONCLUSIONS:
The results of this trial in patients with acute ischemic stroke indicate that endovascular therapy is not superior to standard treatment with intravenous t-PA. (Funded by the Italian Medicines Agency, ClinicalTrials.gov number, NCT00640367.)
Regioirregular and catalytic Mizoroki-Heck reactions
No full text[EN] The palladium-catalysed cross-coupling reaction between alkenes and aryl halides (the Mizoroki-Heck reaction) is a powerful methodology to construct new carbon-carbon bonds. However, the success of this reaction is in part hampered by an extremely marked regioselectivity on the double bond, which dictates that electron-poor alkenes react exclusively on the beta-carbon. Here, we show that ligand-free, few-atom palladium clusters in solution catalyse the alpha-selective intramolecular Mizoroki-Heck coupling of iodoaryl cinnamates, and mechanistic studies support the formation of a sterically encumbered cinnamate-palladium cluster intermediate. Following this rationale, the alpha-selective intermolecular coupling of aryl iodides with styrenes is also achieved with palladium clusters encapsulated within fine-tuned and sterically restricted zeolite cavities to produce 1,1-bisarylethylenes, which are further engaged with aryl halides by a metal-free photoredox-catalysed coupling. These ligand-free methodologies significantly expand the chemical space of the Mizoroki-Heck coupling.This work was supported by MINECO (Spain, projects CTQ 2017-86735-P, PID2019-105391GB-C22 and MAT2017-82288-C2-1-P, Severo Ochoa programme SEV-2016-0683 and the Juan de la Cierva programme). F.G.-P. and R.G. thank ITQ for the concession of a contract. J.O.-M. acknowledges the Juan de la Cierva programme for the concession of a contract, and R.P.-R. and J.C.-S. thank the Plan GenT programme (CIDEGENT/2018/044) funded by Generalitat Valenciana. 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Mechanical ventilation in patients with cardiogenic pulmonary edema: a sub-analysis of the lung safe study
No full textSupported by Centro de Investigación Biomédica en Red (CIBER)‑Enfermedades respiratorias, Madrid, Spain (CB17/06/00021) and Fundación para el Fomento en Asturias de la Investigación Científica aplicada y la tecnología
(FICYT, AYUD2021/52014). RRG is the recipient of a grant from Instituto de Salud Carlos III, Madrid, Spain (CM20/00083).Amado-Rodríguez L., Rodríguez-Garcia R., Bellani G., Pham T., Fan E., Madotto F., Laffey J.G., Albaiceta G.M., Pesenti A., Brochard L., Esteban A., Gattinoni L., van Haren F., Larsson A., McAuley D.F., Ranieri M., Rubenfeld G., Taylor Thompson B., Wrigge H., Slutsky A.S., Rios F., Van Haren F., Sottiaux T., Depuydt P., Lora F.S., Azevedo L.C., Bugedo G., Qiu H., Gonzalez M., Silesky J., Cerny V., Nielsen J., Jibaja M., Wrigge H., Matamis D., Ranero J.L., Amin P., Hashemian S.M., Clarkson K., Kurahashi K., Villagomez A., Zeggwagh A.A., Heunks L.M., Laake J.H., Palo J.E., do Vale Fernandes A., Sandesc D., Arabi Y.M., Bumbasierevic V., Nin N., Lorente J.A., Larsson A., Piquilloud L., Abroug F., McAuley D.F., McNamee L., Hurtado J., Bajwa E., Démpaire G., Sula H., Nunci L., Cani A., Zazu A., Dellera C., Insaurralde C.S., Las Lomas S., Isidro S., Alejandro R.V., Daldin J., Vinzio M., Fernandez R.O., Cardonnet L.P., Bettini L.R., Bisso M.C., Osman E.M., Setten M.G., Lovazzano P., Alvarez J., Villar V., Pozo N.C., Grubissich N., Plotnikow G.A., Vasquez D.N., Ilutovich S., Tiribelli N., Chena A., Pellegrini C.A., Saenz M.G., Estenssoro E., Brizuela M., Gianinetto H., Gomez P.E., Cerrato V.I., Bezzi M.G., Borello S.A., Loiacono F.A., Fernandez A.M., Knowles S., Reynolds C., Inskip D.M., Miller J.J., Kong J., Whitehead C., Bihari S., Seven A., Krstevski A., Rodgers H.J., Millar R.T., McKenna T.E., Bailey I.M., Hanlon G.C., Aneman A., Lynch J.M., Azad R., Neal J., Woods P.W., Roberts B.L., Kol M.R., Wong H.S., Riss K.C., Staudinger T., Wittebole X., Berghe C., Bulpa P.A., Dive A.M., Verstraete R., Lebbinck H., Depuydt P., Vermassen J., Meersseman P., Ceunen H., Rosa J.I., Beraldo D.O., Piras C., Rampinelli A.M., Nassar Jr A.P., Mataloun S., Moock M., Thompson M.M., Gonçalves C.H., Antônio A.C.P., Ascoli A., Biondi R.S., Fontenele D.C., Nobrega D., Sales V.M., BinHJAbul Wahab A.Y., Ismail M., Shindhe S., Laffey J., Beloncle F., Davies K.G., Cirone R., Manoharan V., Ismail M., Goligher E.C., Jassal M., Nishikawa E., Javeed A., Curley G., Rittayamai N., Parotto M., Ferguson N.D., Mehta S., Knoll J., Pronovost A., Canestrini S., Bruhn A.R., Garcia P.H., Aliaga F.A., Farías P.A., Yumha J.S., Ortiz C.A., Salas J.E., Saez A.A., Vega L.D., Labarca E.F., Martinez F.T., Carreño N.G., Lora P., Liu H., Qiu H., Liu L., Tang R., Luo X., An Y., Zhao H., Gao Y., Zhai Z., Ye Z.L., Wang W., Li W., Li Q., Zheng R., Yu W., Shen J., Li X., Yu T., Lu W., Wu Y.Q., Huang X.B., He Z., Lu Y., Han H., Zhang F., Sun R., Wang H.X., Qin S.H., Zhu B.H., Zhao J., Liu J., Li B., Liu J.L., Zhou F.C., Li Q.J., Zhang X.Y., Li-Xin Z., Xin-Hua Q., Jiang L., Gao Y.N., Zhao X.Y., Li Y.Y., Li X.L., Wang C., Yao Q., Yu R., Chen K., Shao H., Qin B., Huang Q.Q., Zhu W.H., Hang A.Y., Hua M.X., Li Y., Xu Y., Di Y.D., Ling L.L., Qin T.H., Wang S.H., Qin J., Han Y., Zhou S., Vargas M.P., Jimenez J.I.S., Rojas M.A.G., SolisQuesada J.E., Ramirez-Alfaro C.M., Máca J., Sklienka P., Gjedsted J., Christiansen A., Nielsen J., Villamagua B.G., Llano I., Burtin P., Buzancais G., Beuret P., Pelletier N., Mortaza S., Mercat A., Chelly J., Jochmans S., Terzi N., Daubin C., Carteaux G., de Prost N., Chiche J.-D., Daviaud F., Fartoukh M., Barberet G., Biehler J., Dellamonica J., Doyen D., Arnal J.-M., Briquet A., Hraiech S., Papazian L., Follin A., Roux D., Messika J., Kalaitzis E., Dangers L., Combes A., Béduneau G., Carpentier D., Zogheib E.H., Dupont H., Ricome S., Santoli F.L., Besset S.L., Michel P., Gelée B., Danin P.-E., Goubaux B., Crova P.J., Phan N.T., Berkelmans F., Badie J.C., Tapponnier R., Gally J., Khebbeb S., Herbrecht J.-E., Schneider F., Declercq P.L.M., Rigaud J.-P., Duranteau J., Harrois A., Chabanne R., Marin J., Bigot C., Thibault S., Ghazi M., Boukhazna M., Zein S.O., Richecoeur J.R., Combaux D.M., Grelon F., Le Moal C., Sauvadet E.P., Robine A., Lemiale V., Reuter D., Dres M., Demoule A., Goldgran-Toledano D., Baboi L., Guérin C., Lohner R., Kraßler J., Schäfer S., Zacharowski K.D., Meybohm P., Reske A.W., Simon P., Hopf H.B.F., Schuetz M., Baltus T., Papanikolaou M.N., Papavasilopoulou T.G., Zacharas G.A., Ourailogloy V., Mouloudi E.K., Massa E.V., Nagy E.O., Stamou E.E., Kiourtzieva E.V., Oikonomou M.A., Avila L.E., Cortez C.A., Citalán J.E., Jog S.A., Sable S.D., Shah B., Gurjar M., Baronia A.K., Memon M., Muthuchellappan R., Ramesh V.J., Shenoy A., Unnikrishnan R., Dixit S.B., Rhayakar R.V., Ramakrishnan N., Bhardwaj V.K., Mahto H.L., Sagar S.V., Palaniswamy V., Ganesan D., Jamaati H., Heidari F., Meaney E.A., Nichol A., Knapman K.M., O’Croinin D., Dunne E.S., Breen D.M., Jaafar R.F., Dwyer R., Amir F., Ajetunmobi O.O., O’Muircheartaigh A.C., Black C.S., Treanor N., Collins D.V., Altaf W., Zani G., Fusari M., Spadaro S., Volta C.A., Graziani R., Brunettini B., Palmese S., Formenti P., Umbrello M., Lombardo A., Pecci E., Botteri M., Savioli M., Protti A., Mattei A., Schiavoni L., Tinnirello A., Todeschini M., Giarratano A., Cortegiani A., Sher S., Rossi A., Antonelli M.M., Montini L.M., Casalena P., Scafetti S., Panarello G., Occhipinti G., Patroniti N., Pozzi M., Biscione R.R., Poli M.M., Raimondi F., Albiero D., Crapelli G., Beck E., Pota V., Schiavone V., Molin A., Tarantino F., Monti G., Frati E., Mirabella L., Cinnella G., Fossali T., Colombo R., Terragni P., Pattarino I., Mojoli F., Braschi A., Borotto E.E., Cracchiolo A.N., Palma D.M., Raponi F., Foti G., Vascotto E.R., Coppadoro A., Brazzi L., Floris L., Iotti G.A., Venti A., Yamaguchi O., Takagi S., Maeyama H.N., Watanabe E., Yamaji Y., Shimizu K., Shiozaki K., Futami S., Ryosuke S., Saito K., Kameyama Y., Ueno K., Izawa M., Okuda N., Suzuki H., Harasawa T., Nasu M., Takada T., Ito F., Nunomiya S., Koyama K., Abe T., Andoh K., Kusumoto K., Hirata A., Takaba A., Kimura H., Matsumoto S., Higashijima U., Honda H., Aoki N., Imai H., Ogino Y., Mizuguchi I., Ichikado K., Nitta K., Mochizuki K., Hashida T., Tanaka H., Nakamura T., Niimi D., Ueda T., Kashiwa Y., Uchiyama A., Sabelnikovs O., Oss P., Haddad Y., Liew K.Y., Ñamendys-Silva S.A., Jarquin-Badiola Y.D., Sanchez-Hurtado L.A., Gomez-Flores S.S., Marin M.C., Lemus J.S., Fierro J.M., Cervantes M.R., Mejia F.J.F., Dector D., Rojas A., Gonzalez D.R., Estrella C.R., Sanchez-Medina J.R., Ramirez-Gutierrez A., George F.G., Aguirre J.S., Buensuseso J.A., Poblano M., Dendane T., Zeggwagh A.A., Balkhi H., Elkhayari M., Samkaoui N., Ezzouine H., Benslama A., Amor M., Maazouzi W., Cimic N., Beck O., Bruns M.M., Schouten J.A., Rinia M., Raaijmakers M., Heunks L.M., Van Wezel H.M., Heines S.J., Strauch U., Buise M.P., Simonis F.D., Schultz M.J., Goodson J.C., Browne T.S., Navarra L., Hunt A., Hutchison R.A., Bailey M.B., Newby L., McArthur C., Kalkoff M., Mcleod A., Casement J., Hacking D.J., Andersen F.H., Dolva M.S., Laake J.H., Barratt-Due A., Noremark K.A.L., Søreide E., Sjøbø B.Å., Guttormsen A.B., LeonYoshido H.H., Aguilar R.Z., Oscanoa F.A.M., Alisasis A.U., Robles J.B., Pasanting-Lim R.A.B., Tan B.C., Andruszkiewicz P., Jakubowska K., Coxo C.M., Alvarez A.M., Oliveira B.S., Montanha G.M., Barros N.C., Pereira C.S., Messias A.M., Monteiro J.M., Araujo A.M., Catorze N.T., Marum S.M., Bouw M.J., Gomes R.M., Brito V.A., Castro S., Estilita J.M., Barros F.M., Serra I.M., Martinho A.M., Tomescu D.R., Marcu A., Bedreag O.H., Papurica M., Corneci D.E., Negoita S.I., Grigoriev E., Gritsan A.I., Gazenkampf A.A., Almekhlafi G., Albarrak M.M., Mustafa G.M., Maghrabi K.A., Salahuddin N., Aisa T.M., AlJabbary A.S., Tabhan E., Trinidad O.A., Al Dorzi H.M., Bumbasirevic V., Jovanovic B., Bolon S., Smith O., Mancebo J., Aguirre-Bermeo H., Lopez-Delgado J.C., Esteve F., Rialp G., Forteza C., De Haro C., Artigas A., Albaiceta G.M., De Cima-Iglesias S., Seoane-Quiroga L., Ceniceros-Barros A., RuizAguilar A.L., Claraco-Vega L.M., Soler J.A., del CarmenLorente M., Hermosa C., Gordo F., PrietoGonzález M., López-Messa J.B., Perez M.P., Perez C.P., Allue R.M., RocheCampo F., Ibañez-Santacruz M., Temprano S., Pintado M.C., De Pablo R., Gómez P.R.A., Ruiz S.R., Moles S.I., Jurado M.T., Arizmendi A., Piacentini E.A., Franco N., Honrubia T., Cheng M.P., Losada E.P., Blanco J., Yuste L.J., Carbayo-Gorriz C., Cazorla-Barranquero F.G., Alonso J.G., Alda R.S., Algaba Á., Navarro G., Cereijo E., Diaz-Rodriguez E., Marcos D.P., Montero L.A., Para L.H., Sanchez R.J., Navalpotro M.A.B., Abad R.D., González R.M., Toribio D.P., Castro A.G., Artiga M.J.D., Penuelas O., Roser T.P., Olga M.F., Curto E.G., Sánchez R.M., Imma V.P., Elisabet G.M., Claverias L., Magret M., Pellicer A.M., Rodriguez L.L., Sánchez-Ballesteros J., González-Salamanca Á., Jimenez A.G., Huerta F.P., Diaz J.C.J.S., Lopez E.B., Moya D.D.L., Alfonso A.A.T., Luis P.S.E., Cesar P.S., Rafael S.I., Virgilio C.G., Recio N.N., Adamsson R.O., Rylander C.C., Holzgraefe B., Broman L.M., Wessbergh J., Persson L., Schiöler F., Kedelv H., Tibblin A.O., Appelberg H., Hedlund L., Helleberg J., Eriksson K.E., Glietsch R., Larsson N., Nygren I., Nunes S.L., Morin A.-K., Kander T., Adolfsson A., Zender H.O., Leemann-Refondini C., Elatrous S., Bouchoucha S., Chouchene I., Ouanes I., Souissi A.B., Kamoun S., Demirkiran O., Aker M., Erbabacan E., Ceylan I., Girgin N.K., Ozcelik M., Ünal N., Meco B.C., Akyol O.O., Derman S.S., Kennedy B., Parhar K., Srinivasa L., McNamee L., McAuley D., Hopkins P., Mellis C., Kakar V., Hadfield D., Vercueil A., Bhowmick K., Humphreys S.K., Ferguson A., Mckee R., Raj A.S., Fawkes D.A., Watt P., Twohey L., Jha R.R., Thomas M., Morton A., Kadaba V., Smith M.J., Hormis A.P., Kannan S.G., Namih M., Reschreiter H., Camsooksai J., Kumar A., Rugonfalvi S., Nutt C., Oneill O., Seasman C., Dempsey G., Scott C.J., Ellis H.E., Mckechnie S., Hutton P.J., Di Tomasso N.N., Vitale M.N., Griffin R.O., Dean M.N., Cranshaw J.H., Willett E.L., Ioannou N., Gillis S., Csabi P., Macfadyen R., Dawson H., Preez P.D., Williams A.J., Boyd O., de Gordoa L.O.-R., Bramall J., Symmonds S., Chau S.K., Wenham T., Szakmany T., Toth-Tarsoly P., McCalman K.H., Alexander P., Stephenson L., Collyer T., Chapman R., Cooper R., Allan R.M., Sim M., Wrathall D.W., Irvine D.A., Zantua C.K.S., Adams J.C., Burtenshaw A.J., Sellors G.P., Welters I.D., Williams K.E., Hessell R.J., Oldroyd M.G., Battle C.E., Pillai S., Kajtor I., Sivashanmugavel M., Okane S.C., Donnelly A., Frigyik A.D., Careless J.P., May M.M., Stewart R., Trinder T.J., Hagan S.J., Cole J.M., MacFie C.C., Dowling A.T., Hurtado J., Nin N., Hurtado J., Nuñez E., Pittini G., Rodriguez R., Imperio M.C., Santos C., França A.G., Ebeid A., Deicas A., Serra C., Uppalapati A., Kamel G., BannerGoodspeed V.M., Beitler J.R., Mukkera S.R., Kulkarni S., Shinn III J.O., Gomaa D., Tainter C., Lee J., Mesar T., Yeatts D.J., Warren J., Lanspa M.J., Miller R.R., Grissom C.K., Brown S.M., Bauer P.R., Gosselin R.J., Kitch B.T., Cohen J.E., Beegle S.H., Choudry S., Gueret R.M., Tulaimat A., Stigler W., Batra H., Huff N.G., Lamb K.D., Oetting T.W., Mohr N.M., Judy C., Saito S., Kheir F.M., Kheir F., Schlichting A.B., Delsing A., Crouch D.R., Elmasri M., Crouch D.R., Ismail D., Dreyer K.R., Blakeman T.C., Baro R.M., Hou P.C., Seethala R., Aisiku I., Henderson G., Frendl G., Hou S.-K., Owens R.L., Schomer A
Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies
No full textBackground: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference –1·69 [–9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5–8] vs 6 [5–8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52–23·52]; p<0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75–0·86]; p<0·0001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding
Mechanical ventilation in patients with cardiogenic pulmonary edema: a sub-analysis of the LUNG SAFE study
No full textBackground: Patients with acute respiratory failure caused by cardiogenic pulmonary edema (CPE) may require mechanical ventilation that can cause further lung damage. Our aim was to determine the impact of ventilatory settings on CPE mortality. Methods: Patients from the LUNG SAFE cohort, a multicenter prospective cohort study of patients undergoing mechanical ventilation, were studied. Relationships between ventilatory parameters and outcomes (ICU discharge/hospital mortality) were assessed using latent mixture analysis and a marginal structural model. Results: From 4499 patients, 391 meeting CPE criteria (median age 70 [interquartile range 59-78], 40% female) were included. ICU and hospital mortality were 34% and 40%, respectively. ICU survivors were younger (67 [57-77] vs 74 [64-80] years, p < 0.001) and had lower driving (12 [8-16] vs 15 [11-17] cmH2O, p < 0.001), plateau (20 [15-23] vs 22 [19-26] cmH2O, p < 0.001) and peak (21 [17-27] vs 26 [20-32] cmH2O, p < 0.001) pressures. Latent mixture analysis of patients receiving invasive mechanical ventilation on ICU day 1 revealed a subgroup ventilated with high pressures with lower probability of being discharged alive from the ICU (hazard ratio [HR] 0.79 [95% confidence interval 0.60-1.05], p = 0.103) and increased hospital mortality (HR 1.65 [1.16-2.36], p = 0.005). In a marginal structural model, driving pressures in the first week (HR 1.12 [1.06-1.18], p < 0.001) and tidal volume after day 7 (HR 0.69 [0.52-0.93], p = 0.015) were related to survival. Conclusions: Higher airway pressures in invasively ventilated patients with CPE are related to mortality. These patients may be exposed to an increased risk of ventilator-induced lung injury. Trial registration Clinicaltrials.gov NCT02010073
Immunocompromised patients with acute respiratory distress syndrome: Secondary analysis of the LUNG SAFE database
No full textBackground: The aim of this study was to describe data on epidemiology, ventilatory management, and outcome of acute respiratory distress syndrome (ARDS) in immunocompromised patients.Methods: We performed a post hoc analysis on the cohort of immunocompromised patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study. The LUNG SAFE study was an international, prospective study including hypoxemic patients in 459 ICUs from 50 countries across 5 continents.Results: Of 2813 patients with ARDS, 584 (20.8%) were immunocompromised, 38.9% of whom had an unspecified cause. Pneumonia, nonpulmonary sepsis, and noncardiogenic shock were their most common risk factors for ARDS. Hospital mortality was higher in immunocompromised than in immunocompetent patients (52.4% vs 36.2%; p < 0.0001), despite similar severity of ARDS. Decisions regarding limiting life- sustaining measures were significantly more frequent in immunocompromised patients (27.1% vs 18.6%; p < 0.0001). Use of noninvasive ventilation (NIV) as first-line treatment was higher in immunocompromised patients (20.9% vs 15.9%; p = 0.0048), and immunodeficiency remained independently associated with the use of NIV after adjustment for confounders. Forty-eight percent of the patients treated with NIV were intubated, and their mortality was not different from that of the patients invasively ventilated ab initio.Conclusions: Immunosuppression is frequent in patients with ARDS, and infections are the main risk factors for ARDS in these immunocompromised patients. Their management differs from that of immunocompetent patients, particularly the greater use of NIV as first-line ventilation strategy. Compared with immunocompetent subjects, they have higher mortality regardless of ARDS severity as well as a higher frequency of limitation of life-sustaining measures. Nonetheless, nearly half of these patients survive to hospital discharge
Resolved versus confirmed ARDS after 24 h: insights from the LUNG SAFE study
No full textPurpose: To evaluate patients with resolved versus confirmed ARDS, identify subgroups with substantial mortality risk, and to determine the utility of day 2 ARDS reclassification.Methods: Our primary objective, in this secondary LUNG SAFE analysis, was to compare outcome in patients with resolved versus confirmed ARDS after 24 h. Secondary objectives included identifying factors associated with ARDS persistence and mortality, and the utility of day 2 ARDS reclassification.Results: Of 2377 patients fulfilling the ARDS definition on the first day of ARDS (day 1) and receiving invasive mechanical ventilation, 503 (24%) no longer fulfilled the ARDS definition the next day, 52% of whom initially had moderate or severe ARDS. Higher tidal volume on day 1 of ARDS was associated with confirmed ARDS [OR 1.07 (CI 1.01-1.13), P = 0.035]. Hospital mortality was 38% overall, ranging from 31% in resolved ARDS to 41% in confirmed ARDS, and 57% in confirmed severe ARDS at day 2. In both resolved and confirmed ARDS, age, non-respiratory SOFA score, lower PEEP and P/F ratio, higher peak pressure and respiratory rate were each associated with mortality. In confirmed ARDS, pH and the presence of immunosuppression or neoplasm were also associated with mortality. The increase in area under the receiver operating curve for ARDS reclassification on day 2 was marginal.Conclusion: ARDS, whether resolved or confirmed at day 2, has a high mortality rate. ARDS reclassification at day 2 has limited predictive value for mortality. The substantial mortality risk in severe confirmed ARDS suggests that complex interventions might best be tested in this population
