30 research outputs found

    Online_supplement_777441 – Supplemental material for Effects of sodium citrate, citric acid and lactic acid on human blood coagulation

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    Supplemental material, Online_supplement_777441 for Effects of sodium citrate, citric acid and lactic acid on human blood coagulation by Vittorio Scaravilli, Luca Di Girolamo, Eleonora Scotti, Mattia Busana, Osvaldo Biancolilli, Patrizia Leonardi, Andrea Carlin, Caterina Lonati, Mauro Panigada, Antonio Pesenti and Alberto Zanella in Perfusion</p

    Approccio metrologico preliminare allo studio delle produzioni dei mattoni cotti a Reggio Calabria tra l’età ellenistica e la prima età romana

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    The richness of brick production in southern Calabria represents one of the most significant aspects of Calabrian Hellenistic cities. The intense building activity, which manifests itself mainly with public building yards but also with private buildings, leads to the development of standardized and peculiar bricks, whose measurements allow in some contexts to determine a modularity. The data coming from the study of fired brick architecture in southern Calabria, in particular between Rhegion/Regium Iulium, its neighboring territories and the Mètauros valley, allow the statistical investigation method to be applied advantageously. From this perspective, the present work aims to analyze the brick supply, and yard systems between the 4th century BC. and the early Roman age through the detailed study of the evolution over time of the thicknesses and modules of the bricks, the result of the interactions between the artisans who work the clay and the sharing of savoir-faire

    Soggettività e Quarto Stato. Modalità della rappresentazione interiore nella narrativa realista e naturalista

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    «La finzione narrativa è il solo luogo conoscitivo in cui l’io di una terza persona può essere presentato nella sua soggettività». È questo l’assunto più importante di Die Logik der Dichtung (1957) di Käte Hamburger, ed è a tali riflessioni che Dorrit Cohn si rifà in Transparent Minds (1978). Nella persuasione che la caratteristica più propria della narrativa di finzione sia la possibilità di rendere trasparente l’interiorità di un eroe epico o romanzesco, permettendo al lettore di partecipare alla soggettività dei personaggi, le due studiose analizzano le modalità attraverso cui la coscienza si manifesta nel dominio narrativo. Si tratta di questioni fondamentali, per anni trascurate dalla critica, che costituiscono lo sfondo teorico del lavoro di tesi, che ha per oggetto la letteratura realista e naturalista. Esso si impernia sulla convinzione che la rappresentazione ʻseriaʼ (nell’accezione auerbachiana) delle coscienze individuali non sia riservata ai personaggi altolocati in maniera esclusiva, bensì accordata, con le dovute differenze di forma e grado, anche agli uomini e alle donne del popolo; e che anzi l’emersione nella diegesi di soggettività socialmente lontane da quella dell’autore sia un aspetto essenziale senza il quale tale produzione non potrebbe intendersi appieno. Tuttavia, sono generalmente necessarie delle condizioni preliminari, che riguardano la caratterizzazione del personaggio di cui l’autore intende condurre l’approfondimento soggettivo. Tali principi si evincono già nel primo case study: I promessi sposi: l’atto fondativo, nella letteratura italiana, della rappresentazione romanzesca degli umili. Sebbene il capolavoro manzoniano si presenti infatti come un caso tipico di romanzo onnisciente, si sono rinvenuti tratti più o meno ampi, nel testo, in cui la voce narrante si ritrae, affidando a un personaggio la centralità della ʻvisioneʼ. Non che l’istanza diegetica rinunci alle impennate didattiche; tuttavia, l’interiorità è riprodotta per mezzo di un’ampia strumentazione di forme. Significativamente, ciò vale soprattutto per Renzo: un contadino filatore di seta costretto, nel suo viaggio fra il contado e Milano, a una sorta di Bildungsroman; un marginale che diventa un piccolo possidente, ma che non subisce un’acculturazione che lo estranei dal suo strato sociale d’origine e lo liberi dalla sua ingenuità. Un personaggio socialmente ibrido, e al confine tra due mondi. È principalmente a caratteri consimili – personaggi che incarnano l’idea della mobilità sociale (declassati, parvenus etc..), o che eccedono la dimensione del quotidiano (operai intellettuali, orfani etc.), facendosi portatori di una devianza – che gli scrittori campagnoli e naturalisti diedero in dote un plot teleologicamente orientato, la possibilità di un destino individuale e la storia di una coscienza. I promessi sposi – insieme a Scènes de la vie de campagne di Honoré de Balzac, e soprattutto il ciclo de Les veillées du chanvreur di George Sand, di cui sono presentate le principali possibilità mimetiche della soggettività popolare – costituirono, oltre che un serbatoio tematico e linguistico, anche il canone della soggettivazione della letteratura «rusticale», che si diffuse nel Lombardo-Veneto durante la lunga vigilia del «decennio di preparazione». Tale produzione fu gravemente ipotecata dalle cautele moderate, che si tradussero, specie nella narrativa di Giulio Carcano, nelle forme limitanti dell’idillio. Si materializzava infatti una nuova esigenza: il bisogno, da parte degli intellettuali, di funzionalizzare le masse rurali nel quadro egemonico della borghesia, di cui questi testi erano più o meno direttamente un’emanazione. Tuttavia, nel concreto della scrittura, gli autori non si limitarono ad esternare una generica compartecipazione emotiva – di segno populistico – nei confronti dei contadini; invece, essi ne dipinsero talvolta le condizioni materiali con piglio obiettivo; e soprattutto si avvalsero delle tecniche della rappresentazione della vita psichica, con cui diedero espressione alla loro soggettività: dolori, emozioni, speranze tradite... Malgrado adotti tutti gli espedienti volti a simulare l’autenticità del loro vissuto interiore, l’autore concede però agli umili un’autonomia narrativa fittizia e tendenziosa. Ciò accade anche in Ippolito Nievo, la cui produzione rusticale, se rapportata al caso di Carcano, è a tratti persino più capziosa, a dispetto del suo fervore democratico e della sua poetica dalla marcata connotazione civile; e ne Le confessioni di un italiano (1857) lo scrittore dedica al popolo uno spazio solo marginale. Ma si sono individuate eccezioni significative: in alcuni racconti di Caterina Percoto l’affiorare della voce dei personaggi popolari mette implicitamente in discussione il sistema valoriale del narratore eterodiegetico, e dunque la Weltanchauung borghese: le istanze pedagogiche convivono problematicamente con la pulsione realistica della scrittrice. L’ultima sezione della tesi prende in esame la letteratura verista e naturalista, che costituisce una specola privilegiata per osservare una svolta che riguardò la narrativa dell’Ottocento nel suo insieme. Da Madame Bovary (1857) in poi, infatti, l’autore sempre più spesso si occulta nel retroscena del testo, affidando a una soggettività diversa dalla sua il compito di mediare al lettore i sensi del racconto. Si tratta di un personaggio (o più di uno) raccontato in terza persona ma che funge da fuoco della rappresentazione: è la situazione narrativa figurale, nel lessico di Franz Karl Stanzel. Il mondo esibito dal testo è il mondo quale appare a tale personaggio, osservato dal suo punto di vista, tinteggiato dalle sue emozioni: molti ritrovati di stile sono adoperati dall’autore a rendere queste percezioni, la realtà quale si riflette nello sguardo di questo terzo, non per nulla definito da Stanzel riflettore. Si parlò al tempo di romanzo psicologico, e l’«analisi psicologica» fu considerata da molti, in Francia come in Italia, una metodica legittima del naturalismo; ma gli scrittori la ritennero idonea, nella loro teoria, solo a determinati personaggi: essenzialmente borghesi, artisti e aristocratici. Il prezzo di una differenza e un pregiudizio di classe. Nondimeno, nella pratica degli autori, la delega al personaggio riflettore non è preclusa ai caratteri del Quarto Stato; e non è infrequente che una soggettività marginale si individualizzi mediante tratti marcati, stagliandosi sulla campitura narratoriale o corale che le fa da sfondo. Attraverso l’analisi di alcuni testi francesi rappresentativi – Germinie Lacerteux (1865) dei fratelli Goncourt, La fortune des Rougon (1871), L’Assommoir (1877), Germinal (1885) e La Terre (1887) di Émile Zola – e una ricognizione della narrativa di Giovanni Verga, Luigi Capuana e Federico De Roberto si è mostrato come i naturalisti attribuiscano, anche ai caratteri del Quarto Stato, un’ʻanimaʼ con cui il lettore è invitato a simpatizzare; scavo analitico che, soprattutto nel caso di Zola, conferisce a tali personaggi una profondità introspettiva autenticamente rivoluzionaria.“Epic fiction is the sole epistemological instance where the I-originarity (or subjectivity) of a third-person qua third-person can be portrayed.” This is the central proposition in Käte Hamburger’s Die Logik der Dichtung (1957), later adopted by Dorrit Cohn as the basis for Transparent Minds (1978). In their view, the most definitive characteristic of narrative fiction is its ability to render the epic or novel hero’s interiority transparent, thus allowing the reader to access the characters’ subjectivity. Through this lens, these two scholars analyze the modalities through which consciousness is manifested in narrative form. These are the fundamental concerns, for years overlooked by criticism, which constitute the theoretical basis of this thesis. Through close readings of Realist and Naturalist literature, this thesis argues that “serious” representation (in the Auerbachian sense) of individual consciousness is not reserved exclusively to upper-class characters, but is also granted to the men and women of the popolo, with necessary differences in degree and form. The emergence in the diegesis of a subjectivity socially distant from that of the author’s is an essential issue without which such works could not be fully understood. However, some preliminary conditions are necessary, which concern the type of the character entrusted to mediate the story to the reader. These principles emerge in the first case study: I promessi sposi, Italian literature’s foundational text for the representation of the poor in the novel. Although Manzoni’s masterpiece may appear to be the exemplary omniscient novel, there are many instances found in the text in which the narrating voice withdraws, entrusting the central perspective to a character. Although these diegetic instants do not eschew their typical didactic flourish, interiority is reproduced through extensive formal techniques. This is notably applied to Renzo, the peasant silk-weaver compelled in his journey from the countryside to Milan into a sort of Bildungsroman: he is a figure from the periphery figure who becomes a small landowner. However, he does not ultimately undergo an acculturation which might estrange him from his original social strata and rescue him from aivety. It is mainly to characters similar to Renzo that rustic literature writers and naturalist writers reserved the “serious” representation of character’s subjectivity. These are characters who embody the idea of social mobility (downgraded, parvenus, etc.) or who exceed the dimension of everyday life (intellectual heroes, orphans, etc.). I promessi sposi, along with Scènes de la vie de campagne by Honoré de Balzac and the Les veillées du chanvreur cycle by George Sand, demonstrate the scope of mimetic representation of the poor. More than a cistern of themes and style, these works form the canon of subjectivation in rustic literature, which spread in Lombardy and Veneto during the long eve of the decennio di preparazione. These works were severely beholden to moderate safeguards, which appear, notably in Giulio Carcano’s narratives, in the restricting forms of the idyllic. A new demand had materialized. Intellectuals needed to make the rural masses function in the hegemonic framework of the bourgeoisie, from which these texts directly emanated. However, in their writings, these authors do not restrict their representation of the peasantry as a vehicle for general emotions, to a token populism. Often, they portrayed their material conditions with an objective lens. Most notably, they utilized techniques to represent psychic life, with which they granted their characters’ subjectivity expression: their pains, their emotions, and their hopes betrayed. It becomes a question of other-directed characters. Despite employing countless devices to simulate authentic interior lives, the author gave the poor an artificial and tendentious narrative autonomy. The contents of their thoughts instrumentally serve the purpose which the writer aims to communicate. However, there are significant, individual exceptions: in some stories by Caterina Percoto, the introduction of popular characters’ voices implicitly challenges the heterodiegetic narrator’s value system, and by extension the bourgeois Weltanchauung. Meanwhile, in the Novelliere campanguolo, Ippolito Nievo assigns the récit to a yokel, who expresses his class grievances in the first person. This narrative phenomenology is later revived, from a bourgeois perspective, in Le confessioni d’un Italiano (1867). The final section of this thesis examines Verist and Naturalist literature, which constitute an excellent specola for observing a turning point in 19th century narrative at large. From Madame Bovary (1857) onwards, the author increasingly withdrew into the backdrop of the text, entrusting a subjectivity other than their own with mediating the story’s consciousness to the reader. It becomes a matter of one or more characters who, despite being described in the third person, focalize the narrative; in Franz Karl Stanzel’s terminology, this is an instance of figural narrative situation. The world depicted in the text is the world as it appears to a certain character, observed from their point of view, and tinted by their emotions; authors adopt a variety of stylistics to render this perception, the reality reflected in the gaze of this third person, uncoincidentally named the “reflector” by Stanzel. He discussed this concept in the age of the psychological novel, when the «psychological analysis» was considered by many, in France as in Italy, as a legitimate methodology of naturalism. Writers, on the other hand, conceived that it was only suitable to employ it for specific characters (primarily the bourgeoisie, artists, and aristocrats); this is the price of disparity and a class prejudice. Nevertheless, in these authors’ writings, numerous points of discontinuity emerged. The delegation of the reflector was not precluded to figures from the Fourth Estate. Moreover, marginal subjectivities are individualized through pronounced traits, silhouetted on a narrative or choral background. Through analysis of some representative French texts – Germinie Lacerteux (1865) by the brothers Goncourt, La fortune des Rougon (1877), L’assommoir (1877), Germinal (1885), and La terre (1887) by Émile Zola – and a survey of the narratives of Giovanni Verga, Luigi Capuana, and Federico De Roberto, it is shown how the naturalists attributed a “soul” to each character, with which the reader is encouraged to sympathize.«La fiction est le seul espace cognitif où le je-origine d’une tierce-personne peut être représenté dans sa subjectivité». C’est là la thèse la plus importante de Die Logik der Dichtung (1957) de Käte Hamburger et ce sont ces considérations auxquelles se réfère Dorrit Cohn dans Transparent Minds (1978). Fortes de la conviction que la caractéristique la plus propre de la fiction est la possibilité de rendre transparente l’intériorité d’un héros épique ou romanesque, en permettant ainsi au lecteur de participer à la subjectivité des personnages, les deux chercheuses analysent les modalités à travers lesquelles la conscience se manifeste dans le domaine narratif. Il s’agit de questions fondamentales, longtemps négligées par la critique, qui constituent l’arrière-plan théorique de ma thèse, qui a pour objet la littérature réaliste et naturaliste. Elle est axée sur la conviction que la représentation ‘sérieuse’ (dans l’acception d’Auerbach) des consciences individuelles n’est pas exclusivement réservée aux personnages haut placés, mais plutôt accordée également, avec les différences de forme et de grade qui s’imposent, aux hommes et aux femmes du peuple ; et que, au contraire, l’émersion dans la diégèse de subjectivités socialement éloignées de celle de l’auteur est un aspect essentiel sans lequel une telle production ne pourrait pas être pleinement comprise. Toutefois, quelques conditions préliminaires, qui concernent la caractérisation du personnage dont le rôle est de transmettre les sens du récit au lecteur, sont nécessaires. Ces principes peuvent être déduits à partir de la première étude de cas : I promessi sposi: l’acte fondateur, dans la littérature italienne, de la représentation romanesque des humbles. Bien que le chef-d’œuvre de Manzoni se présente comme un cas typique de roman omniscient, nous avons repéré des passages plus ou moins longs, dans le texte, où la voix du narrateur se retire pour confier à un personnage la centralité de la ‘vision’. Ce n’est pas que l’instance diégétique renonce aux interventions didactiques ; toutefois, l’intériorité est reproduite au moyen de nombreux instruments formels. Cela vaut surtout pour Renzo : un paysan fileur de soie contraint, lors de son voyage entre la campagne et Milan, de vivre une sorte de Bildungsroman ; un marginal qui devient un petit propriétaire, mais qui ne subit pas une acculturation suffisante pour l’éloigner de sa couche sociale d’origine et le libérer de sa naïveté. Un personnage socialement hybride, à la frontière entre deux mondes. C’est essentiellement ce genre de personnages – des personnages qui incarnent l’idée de la mobilité sociale (déclassés, parvenus, etc.), ou qui dépassent la dimension du quotidien (ouvriers intellectuels, orphelins, etc.), en mettant l’accent sur une déviance – que les écrivains champêtres et naturalistes ont doté de la possibilité du traitement subjectif ‘sérieux’. I promessi sposi – avec Scènes de la vie de campagne d’Honoré de Balzac et surtout le cycle Les veillées du chanvreur de George Sand, dont les principales possibilités mimétiques de la subjectivité populaire sont ici présentées – ont constitué, en plus d’un réservoir thématique et linguistique, le canon de la subjectivation de la littérature « rustique » qui s’est répandue en Lombardie et en Vénétie à la veille de la « décennie de préparation ». Cette production a été gravement hypothéquée par les précautions modérées qui se sont traduites, notamment dans la narrative de Giulio Carcano, dans les formes limitantes de l’idylle. Une nouvelle exigence venait en effet de se matérialiser : le besoin, de la part des intellectuels, de fonctionnaliser les masses rurales dans le contexte hégémonique de la bourgeoisie, dont ces textes constituaient, plus ou moins directement, une émanation. Toutefois, dans le concret de l’écriture, les auteurs ne se sont pas limités à exprimer une participation émotionnelle générique – d’orientation populiste – à l’égard des paysans : au contraire, ils en ont quelques fois dépeint les conditions matérielles de façon objective ; et surtout ils ont employé les techniques de la représentation de la vie psychique, avec lesquelles ils ont donné forme à leur subjectivité : douleurs, émotions, espoirs trahis... Bien que tous les moyens visant à simuler l’authenticité du vécu intérieur de ces personnages aient été adoptés, le contenu de leurs pensées est utilisé de manière instrumentale, afin de répondre au but que l’auteur entend propager. Quelques exceptions significatives ont toutefois été décelées : dans certains récits de Caterina Percoto, l’émergence de la voix des personnages populaires remet implicitement en question le système de valeurs du narrateur hétérodiégétique et donc la Weltanchauung bourgeoise. La dernière section de ma thèse examine la littérature vériste et naturaliste, qui constitue une perspective privilégiée pour observer un tournant de la narrative du XIXe siècle dans son ensemble. A partir de Madame Bovary (1857), en effet, l’auteur se camoufle de plus en plus souvent dans les coulisses du texte, en confiant à une subjectivité différente de la sienne la tâche de transmettre au lecteur les sens du récit. La narration est à la troisième personne, mais il y a un personnage qui sert de focus à la représentation : c’est la situation narrative figurale, dans le lexique de Franz Karl Stanzel. Le monde présenté par le texte est le monde tel qu’il apparaît à ce personnage, observé depuis son point de vue, teinté de ses émotions : de nombreuses inventions de style sont employées par l’auteur afin de rendre ces perceptions, la réalité comme elle se reflète dans le regard de ce tiers, défini non sans raison réflecteur par Stanzel. A l’époque, on a parlé de roman psychologique et l’ « analyse psychologique » a été considérée par un grand nombre de écrivains, en France comme en Italie, une méthodologie légitime du naturalisme ; mais les écrivains ont estimé qu’elle n’était appropriée, dans leur théorie, qu’à certains personnages : essentiellement des bourgeois, des artistes et des aristocrates. Le prix d’une différence et d’un préjugé de classe. Malgré tout, dans la pratique des auteurs, de nombreux points de rupture sont apparus : en effet, déléguer la focalisation n’est pas une opération qui exclut les personnages du quatrième état ; et il n’est pas rare qu’une subjectivité marginale s’individualise au moyen de traits marqués, en se détachant du fond choral ou objectif. A travers l’analyse de certains textes français représentatifs – Germinie Lacerteux (1865) des frères Goncourt, La fortune des Rougon (1871), L’Assommoir (1877), Germinal (1885) et La Terre (1887) d’Émile Zola – et une exploration des récits de Giovanni Verga, Luigi Capuana et Federico De Roberto, nous avons montré que les naturalistes attribuent, même aux personnages du Quatrième Etat, une ʻâmeʼ avec laquelle le lecteur est invité à sympathiser, en leur accordant, parfois sur de longues portions (notamment chez Zola), une profondeur introspective véritablement révolutionnaire

    Nosocomial infections during extracorporeal membrane oxygenation: Incidence, etiology, and impact on patients' outcome

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    Objective: To study incidence, type, etiology, risk factors, and impact on outcome of nosocomial infections during extracorporeal membrane oxygenation. Design: Retrospective analysis of prospectively collected data. Setting: Italian tertiary referral center medical-surgical ICU. Patients: One hundred five consecutive patients who were treated with extracorporeal membrane oxygenation from January 2010 to November 2015. Interventions: None. Measurements and Main Results: Ninety-two patients were included in the analysis (48.5 [37-56] years old, simplified acute physiology score II 37 [32-47]) who underwent peripheral extracorporeal membrane oxygenation (87% veno-venous) for medical indications (78% acute respiratory distress syndrome). Fifty-two patients (55%) were infected (50.4 infections/1,000 person-days of extracorporeal membrane oxygenation). We identified 32 ventilator-associated pneumonia, eight urinary tract infections, five blood stream infections, three catheter-related blood stream infections, two colitis, one extracorporeal membrane oxygenation cannula infection, and one pulmonary-catheter infection. G+ infections (35%) occurred earlier compared with G- (48%) (4 [2-10] vs. 13 [7-23] days from extracorporeal membrane oxygenation initiation; p 50 years old), reason for connection different from acute respiratory distress syndrome, higher simplified acute physiology score II, diagnosis of ventilator-associated pneumonia, and infection by multidrug-resistant bacteria were independently associated to increased death rate. Conclusions: Infections (especially ventilator-associated pneumonia) during extracorporeal membrane oxygenation therapy are common and frequently involve multidrug-resistant organisms. In addition, they have a negative impact on patients' outcomes

    PCSK9 is associated with mortality in patients with septic shock: data from the ALBIOS study

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    Background: Pro-protein convertase subtilisin/kexin 9 (PCSK9) is a proenzyme primarily known to regulate low-density lipoprotein receptor re-uptake on hepatocytes. Whether PCSK9 can concurrently trigger inflammation or not remains unclear. Here, we investigated the potential association between circulating levels of PCSK9 and mortality in patients with severe sepsis or septic shock. Methods: Plasma PCSK9 levels at days 1, 2 and 7 were measured in 958 patients with severe sepsis or septic shock previously enrolled in the Albumin Italian Outcome Sepsis (ALBIOS) trial. Correlations between levels of PCSK9 and pentraxin 3 (PTX3), a biomarker of disease severity, were evaluated with ranked Spearman's coefficients. Cox proportional hazards models were used to assess the association of PCSK9 levels at day 1 with 28- and 90-day mortality. Results: Median plasma PCSK9 levels were 278 [182-452] ng mL-1 on day 1. PCSK9 correlated positively with PTX3 at the three time-points, and patients with septic shock within the first quartile of PCSK9 showed higher levels of PTX3. Similar mortality rates were observed in patients with severe sepsis across PCSK9 quartiles. Patients with septic shock with lower PCSK9 levels on day 1 (within the first quartile) showed the highest 28- and 90-day mortality rate as compared to other quartiles. Conclusion: In our sub-analysis of the ALBIOS trial, we found that patients with septic shock presenting with lower plasma PCSK9 levels experienced higher mortality rate. Further studies are warranted to better evaluate the pathophysiological role of PCSK9 in sepsis

    Effects of sodium citrate, citric acid and lactic acid on human blood coagulation

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    Introduction: Citric acid infusion in extracorporeal blood may allow concurrent regional anticoagulation and enhancement of extracorporeal CO2removal. Effects of citric acid on human blood thromboelastography and aggregometry have never been tested before. Methods: In this in vitro study, citric acid, sodium citrate and lactic acid were added to venous blood from seven healthy donors, obtaining concentrations of 9 mEq/L, 12 mEq/L and 15 mEq/L. We measured gas analyses, ionized calcium (iCa++) concentration, activated clotting time (ACT), thromboelastography and multiplate aggregometry. Repeated measure analysis of variance was used to compare the acidifying and anticoagulant properties of the three compounds. Results: Sodium citrate did not affect the blood gas analysis. Increasing doses of citric and lactic acid progressively reduced pH and HCO3−and increased pCO2(p600 sec at 15 mEq/L (p<0.001). Lactic acid did not affect the ACT values (p=0.486). Sodium citrate and citric acid similarly incremented R-time and reduced α-angle and maximum amplitude (MA) (p<0.001), leading to flat-line thromboelastograms at 15 mEq/L. Platelet aggregometry was not altered by any of the three compounds. Conclusions: Citric acid infusions determine acidification and anticoagulation of blood similar to lactic acid and sodium citrate, respectively

    Use of high flow nasal cannula in patients with acute respiratory failure in general wards under intensivists supervision: a single center observational study

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    BACKGROUND: Few data exist on high flow nasal cannula (HFNC) use in patients with acute respiratory failure (ARF) admitted to general wards. RATIONALE AND OBJECTIVES: To retrospectively evaluate feasibility and safety of HFNC in general wards under the intensivist-supervision and after specific training. METHODS: Patients with ARF (dyspnea, respiratory rate-RR > 25/min, 150 < PaO(2)/FiO(2) < 300 mmHg during oxygen therapy) admitted to nine wards of an academic hospital were included. Gas-exchange, RR, and comfort were assessed before HFNC and after 2 and 24 h of application. RESULTS: 150 patients (81 male, age 74 [60–80] years, SOFA 4 [2–4]), 123 with de-novo ARF underwent HFNC with flow 60 L/min [50–60], FiO(2) 50% [36–50] and temperature 34 °C [31–37]. HFNC was applied a total of 1399 days, with a median duration of 7 [3–11] days. No major adverse events or deaths were reported. HFNC did not affect gas exchange but reduced RR (25–22/min at 2–24 h, p < 0.001), and improved Dyspnea Borg Scale (3–1, p < 0.001) and comfort (3–4, p < 0.001) after 24 h. HFNC failed in 20 patients (19.2%): 3 (2.9%) for intolerance, 14 (13.4%) escalated to NIV/CPAP in the ward, 3 (2.9%) transferred to ICU. Among these, one continued HFNC, while the other 2 were intubated and they both died. Predictors of HFNC failure were higher Charlson’s Comorbidity Index (OR 1.29 [1.07–1.55]; p = 0.004), higher APACHE II Score (OR 1.59 [1.09–4.17]; p = 0.003), and cardiac failure as cause of ARF (OR 5.26 [1.36–20.46]; p = 0.02). CONCLUSION: In patients with mild-moderate ARF admitted to general wards, the use of HFNC after an initial training and daily supervision by intensivists was feasible and seemed safe. HFNC was effective in improving comfort, dyspnea, and respiratory rate without effects on gas exchanges. Trial registration This is a single-centre, noninterventional, retrospective analysis of clinical data. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-022-02090-x

    A Minimally Invasive and Highly Effective Extracorporeal CO2 Removal Device Combined With a Continuous Renal Replacement Therapy

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    Objectives: Extracorporeal carbon dioxide removal is used to treat patients suffering from acute respiratory failure. However, the procedure is hampered by the high blood flow required to achieve a significant CO2 clearance. We aimed to develop an ultralow blood flow device to effectively remove CO2 combined with continuous renal replacement therapy (CRRT). Design: Preclinical, proof-of-concept study. Setting: An extracorporeal circuit where 200 mL/min of blood flowed through a hemofilter connected to a closed-loop dialysate circuit. An ion-exchange resin acidified the dialysate upstream, a membrane lung to increase PCO2 and promote CO2 removal. Patients: Six, 38.7 ± 2.0-kg female pigs. Interventions: Different levels of acidification were tested (from 0 to 5 mEq/min). Two l/hr of postdilution CRRT were performed continuously. The respiratory rate was modified at each step to maintain arterial PCO2 at 50 mm Hg. Measurements and main results: Increasing acidification enhanced CO2 removal efficiency of the membrane lung from 30 ± 5 (0 mEq/min) up to 145 ± 8 mL/min (5 mEq/min), with a 483% increase, representing the 73% ± 7% of the total body CO2 production. Minute ventilation decreased accordingly from 6.5 ± 0.7 to 1.7 ± 0.5 L/min. No major side effects occurred, except for transient tachycardia episodes. As expected from the alveolar gas equation, the natural lung PaO2 dropped at increasing acidification steps, given the high dissociation between the oxygenation and CO2 removal capability of the device, thus PaO2 decreased. Conclusions: This new extracorporeal ion-exchange resin-based multiple-organ support device proved extremely high efficiency in CO2 removal and continuous renal support in a preclinical setting. Further studies are required before clinical implementation

    Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study

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    Background Patients with COVID-19 can develop acute respiratory distress syndrome (ARDS), which is associated with high mortality. The aim of this study was to examine the functional and morphological features of COVID-19-associated ARDS and to compare these with the characteristics of ARDS unrelated to COVID-19.Methods This prospective observational study was done at seven hospitals in Italy. We enrolled consecutive, mechanically ventilated patients with laboratory-confirmed COVID-19 and who met Berlin criteria for ARDS, who were admitted to the intensive care unit (ICU) between March 9 and March 22, 2020. All patients were sedated, paralysed, and ventilated in volume-control mode with standard ICU ventilators. Static respiratory system compliance, the ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air, ventilatory ratio (a surrogate of dead space), and D-dimer concentrations were measured within 24 h of ICU admission. Lung CT scans and CT angiograms were done when clinically indicated. A dataset for ARDS unrelated to COVID-19 was created from previous ARDS studies. Survival to day 28 was assessed.Findings Between March 9 and March 22, 2020, 301 patients with COVID-19 met the Berlin criteria for ARDS at participating hospitals. Median static compliance was 41 mL/cm H2O (33–52), which was 28% higher than in the cohort of patients with ARDS unrelated to COVID-19 (32 mL/cm H2O [25–43]; p&lt;0·0001). 17 (6%) of 297 patients with COVID-19-associated ARDS had compliances greater than the 95th percentile of the classical ARDS cohort. Total lung weight did not differ between the two cohorts. CT pulmonary angiograms (obtained in 23 [8%] patients with COVID-19-related ARDS) showed that 15 (94%) of 16 patients with D-dimer concentrations greater than the median had bilateral areas of hypoperfusion, consistent with thromboembolic disease. Patients with D-dimer concentrations equal to or less than the median had ventilatory ratios lower than those of patients with D-dimer concentrations greater than the median (1·66 [1·32–1·95] vs 1·90 [1·50–2·33]; p=0·0001). Patients with static compliance equal to or less than the median and D-dimer concentrations greater than the median had markedly increased 28-day mortality compared with other patient subgroups (40 [56%] of 71 with high D-dimers and low compliance vs 18 [27%] of 67 with low D-dimers and high compliance, 13 [22%] of 60 with low D-dimers and low compliance, and 22 [35%] of 63 with high D-dimers and high compliance, all p=0·0001).Interpretation Patients with COVID-19-associated ARDS have a form of injury that, in many aspects, is similar to that of those with ARDS unrelated to COVID-19. Notably, patients with COVID-19-related ARDS who have a reduction in respiratory system compliance together with increased D-dimer concentrations have high mortality rate
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