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Sepsis is defined as a life-threatening organ dysfunction induced by a dysregulated host immune response to infection. Immune response induced by sepsis is complex and dynamic. It is schematically described as an early dysregulated systemic inflammatory response leading to organ failures and early deaths, followed by the development of persistent immune alterations affecting both the innate and adaptive immune responses associated with increased risk of secondary infections, viral reactivations, and late mortality. In this review, we will focus on the role of NACHT, leucin-rich repeat and pyrin-containing protein 3 (NLRP3) inflammasome in the pathophysiology of sepsis. NLRP3 inflammasome is a multiproteic intracellular complex activated by infectious pathogens through a two-step process resulting in the release of the pro-inflammatory cytokines IL-1β and IL-18 and the formation of membrane pores by gasdermin D, inducing a pro-inflammatory form of cell death called pyroptosis. The role of NLRP3 inflammasome in the pathophysiology of sepsis can be ambivalent. Indeed, although it might protect against sepsis when moderately activated after initial infection, excessive NLRP3 inflammasome activation can induce dysregulated inflammation leading to multiple organ failure and death during the acute phase of the disease. Moreover, this activation might become exhausted and contribute to post-septic immunosuppression, driving impaired functions of innate and adaptive immune cells. Targeting the NLRP3 inflammasome could thus be an attractive option in sepsis either through IL-1β and IL-18 antagonists or through inhibition of NLRP3 inflammasome pathway downstream components. Available treatments and results of first clinical trials will be discussed.

Breast cancer is the most prevalent neoplasm in women in North American and European countries. Data about intensive care unit (ICU) requirements and the related outcomes are scarce. Furthermore, long-term outcome after ICU discharge has not been described. We conducted a retrospective monocenter study including patients with breast cancer requiring unplanned ICU admission over a 14-year period (2007–2020). 177 patients (age = 65[57–75] years) were analyzed. Breast cancer was at a metastatic stage for 122 (68.9%) patients, recently diagnosed in 25 (14.1%) patients or in progression under treatment in 76 (42.9%) patients. Admissions were related to sepsis in 56 (31.6%) patients, to iatrogenic/procedural complication in 19 (10.7%) patients and to specific oncological complications in 47 (26.6%) patients. Seventy-two (40.7%) patients required invasive mechanical ventilation, 57 (32.2%) vasopressors/inotropes, and 26 (14.7%) renal replacement therapy. In-ICU and one-year mortality rates were 20.9% and 57.1%, respectively. Independent factors associated with in-ICU mortality were invasive mechanical ventilation and impaired performance status. One-year mortality in ICU survivors was independently associated with specific complications, triple negative cancer, and impaired performance status. After hospital discharge, most patients (77.4%) were able to continue or initiate antitumoral treatment. ICU admission was linked to the underlying malignancy in one-quarter of breast cancer patients. Despite the low in-ICU mortality rate (20.9%) and thereafter continuation of cancer treatment in most survivors (77.4%), one-year mortality reached 57.1%. Impaired performance status prior to the acute complication was a potent predictor of both short-term and long-term outcomes.

Simple and accessible prognostic factors are paramount for solid cancer patients experiencing life-threatening complications. The aim of this study is to appraise the impact of functional and nutritional status and skeletal muscle mass in this population. We conducted a retrospective (2007–2020) single-center study by enrolling adult patients with solid cancers requiring unplanned ICU admission. Performance status, body weight, and albumin level were collected at ICU admission and over six months. Skeletal muscle mass was assessed at ICU admission by measuring muscle areas normalized by height (SMI). Four-hundred and sixty-two patients were analyzed, mainly with gastro-intestinal (34.8%) and lung (29.9%) neoplasms. Moreover, 92.8% of men and 67.3% of women were deemed cachectic. In the multivariate analysis, performance status at ICU admission (CSH 1.74 [1.27–2.39], p < 0.001) and the six month increase in albumin level (CSH 0.38 [0.16–0.87], p = 0.02) were independent predictors of ICU mortality. In the subgroup of mechanically ventilated patients, the psoas SMI was independently associated with ICU mortality (CSH 0.82 [0.67–0.98], p = 0.04). Among the 368 ICU-survivors, the performance status at ICU admission (CSH 1.34 [1.14–1.59], p < 0.001) and the six-month weight loss (CSH 1.33 [1.17–2.99], p = 0.01) were associated with a one-year mortality rate. Most cancer patients displayed cachexia at ICU admission. Time courses of nutritional parameters may aid the prediction of short- and long-term outcomes.

Sepsis and cancer share a number of pathophysiological features, and both result from the inability of the host's immune system to cope with the initial insult (tissue invasion by pathogens and malignant cell transformation, respectively). The common coexistence of both disorders and the profound related alterations in immune homeostasis raise the question of their mutual impact on each other's course. This translational review aims to discuss the interactions between cancer and sepsis supported by clinical data and the translation to experimental models. The dramatic improvement in cancer has come at a cost of increased risks of life-threatening infectious complications. Investigating the long-term outcomes of sepsis survivors has revealed an unexpected susceptibility to cancer long after discharge from the ICU. Nonetheless, it is noteworthy that an acute septic episode may harbor antitumoral properties under particular circumstances. Relevant double-hit animal models have provided clues to whether and how bacterial sepsis may impact malignant tumor growth. In sequential sepsis-then-cancer models, postseptic mice exhibited accelerated tumor growth. When using reverse cancer-then-sepsis models, bacterial sepsis applied to mice with cancer conversely resulted in inhibition or even regression of tumor growth. Experimental models thus highlight dual effects of sepsis on tumor growth, mostly depending on the sequence of insults, and allow deciphering the immune mechanisms and their relation with microorganisms.

Transfusion-related acute lung injury (TRALI), defined as the onset of acute respiratory distress after blood transfusion, is a rare complication which is a leading cause of transfusion related-mortality. In this retrospective study, we report the French nationwide experience of intravenous immunoglobulin (IVIG)-related TRALI, with a literature review and analysis of management and outcome of this rare condition. With the pharmacovigilance services, we conducted a retrospective multicenter study in the French network of intensive care units with TRALI concomitant to IVIG use and pooled with data from a literature review. Overall, 17 cases have been included in this case-series, our case report, seven personal cases and nine cases from the literature review. The median age was 55 years [2-79] with 10/17 (59%) male subjects. The underlying diseases motivating IVIG infusion were neurologic diseases in 35% of cases (Guillain Barre syndrome = 2, peripheral neuropathy = 2, neurolupus = 1, myasthenia = 1), multiple myeloma with hypogammaglobulinemia (n = 2; 12%), primary hypogammaglobulinemia (n = 2; 12%), autoimmune cytopenias (n = 2; 12%), graft versus host cutaneous disease after allogeneic hematopoietic stem cell transplantation for acute myeloid leukaemia (n = 1), anti-HLA antibodies after lung transplant (n = 1), cancer-associated thrombotic thrombocytopenic purpura-haemolytic uremic syndrome (n = 1), Kawasaki disease (n = 1) and in experimental essay (n = 1). TRALI symptoms begin either after the start or during the infusion (n = 7; 41%), or after the infusion (n = 10; 59%, 10 min to 24 h). Besides respiratory distress, it was also noted shock (33%), fever (18 %), cough (18%), nausea/vomiting (18 %), chills (12%) and agitation (12%). The X-ray showed mainly bilateral alveolar opacities (n = 15; 88%). Mechanical ventilation was needed in nine cases (53%), with median 1-day duration [1-4]. Four patients (24%) died during hospitalisation in the intensive care unit. Given the increasing use of intravenous immunoglobulins, TRALI must now be discussed in cases of respiratory distress occurring during or immediately following the infusion even if this side effect remains rare.Key Points• TRALI must now be discussed in cases of respiratory distress occurring during or immediately following an infusion of intravenous immunoglobulins.

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Ventilator-associated pneumonia (VAP) increases exposure to antibiotics. Physicians are however reluctant to shorten treatment, arguing this could lead to failures and worse outcome. Monitoring procalcitonin (PCT) has proven effective for decreasing exposure to antibiotics in randomized controlled trials, but additional "real-life" studies are needed.All patients with VAP in whom ABT was stopped before death or discharge were included in this 5-year prospective cohort study. Patients in whom ABT was stopped in accordance with the algorithm ("PCT-guided" group: ABT withdrawal strongly encouraged if PCT 0.5 ng/mL or 80% peak value) were compared to those with ABT continuation despite PCT decrease ("not PCT-guided" group). The primary endpoint was ABT duration. The secondary endpoint was unfavorable VAP outcome (i.e. death or relapse).We included 157 of the 316 patients with microbiologically-proven VAP. The algorithm was overruled in 81 patients (51.6%). ABT duration was significantly longer in these patients than in the PCT-guided group (9.5 vs. 8.0 days; p = .02), although baseline and VAP characteristics did not differ. The rate of unfavorable outcomes was comparable (46.9% vs. 51.3%; p = .69).PCT-guided ABT adherence appears safe for patients with VAP and is likely to reduce exposure to antibiotics.

BACKGROUND Bradykinin-mediated angioedema (AE) is a complication associated with thrombolysis for acute ischemic stroke. Risk factors are unknown and management is discussed. OBJECTIVES To clarify risk factors associated with bradykinin-mediated AE after thrombolysis for acute ischemic stroke. METHODS In a case-control study conducted at a French reference centre for bradykinin angiœdema, patients with thrombolysis for acute ischemic stroke and a diagnosis of bradykinin-mediated angiœdema, were compared to controls treated with thrombolysis treatment without angiœdema. RESULTS Fifty-three thrombolysis-related AE were matched to 106 control subjects. The sites of attacks following thrombolysis for ischemic stroke mainly included tongue (34/53, 64%) and lips (26/53, 49%). The upper airways were involved in 37 (70%) cases. Three patients required mechanical ventilation. Patients with bradykinin-mediated angiœdema were more frequently women [33 (62%) vs. 44 (42%); P = 0.01], had higher frequency of prior ischemic stroke [12 (23%) vs. 9 (8%); P = 0.01], hypertension [46 (87%) vs. 70 (66%); P = 0.005], were more frequently treated with angiotensin-converting enzyme inhibitor [37 (70%) vs. 28 (26%); P

Introduction Le TRALI est defini par une insuffisance respiratoire aigue survenant dans les 6 h apres transfusion de produits sanguins avec infiltrats pulmonaires bilateraux a la radiographie thoracique, sans argument pour une surcharge cardiaque. Les mecanismes imputables sont l’activation de la degranulation des neutrophiles au niveau pulmonaire, en lien avec des anticorps anti-neutrophiles du donneur, l’apport de lipides bioactifs accumules durant la conservation des produits sanguins et l’injection d’anticorps anti-HLA de classe I ou II [1] . Bien que l’etiologie la plus frequente soit la transfusion de concentres de globules rouges, le premier cas de TRALI apres immunoglobulines intraveineuses (IgIV) a ete decrit en 1997 [2] . Les caracteristiques cliniques et le pronostic des TRALI lies aux IgIV sont mal connus. Patients et methodes Nous avons mene une etude retrospective multicentrique dans les reanimations francaises de TRALI lies aux IgIV. Les criteres d’inclusion etaient : l’utilisation d’IgIV maximum 24 h avant la survenue du TRALI, qui etait defini par une hypoxemie aigue (saturation inferieure a 90 % ou rapport PaO2/FiO2 inferieur a 300 mmHg) avec des infiltrats pulmonaires bilateraux a la radiographie thoracique, sans argument pour une surcharge cardiaque. Les donnees clinico-biologiques, les resultats de l’echocardiographie cardiaque transthoracique (ETT), les traitements, les suppleances d’organe et le pronostic etaient recueillis. La revue de la litterature a ete effectuee par 2 investigateurs via Pubmed, Embase, Scopus, Web of Science et la Cochrane library, en utilisant les mots-cles « intravenous immunoglobulins », « TRALI », « transfusion-related lung injury », « adverse events ». Resultats Huit cas de 8 reanimations ont ete collectes entre janvier 2010 et janvier 2016 et 9 cas ont ete retrouves dans litterature, soit 17 cas pooles dans cette serie de cas. Les pathologies justifiant l’administration d’IgIV etaient des pathologies neurologiques dans 35 % des cas, des hypogammaglobulinemies dans le cadre de myelome multiple dans 12 % des cas, des hypogammaglobulinemies primaires dans 12 % des cas, des cytopenies auto-immunes dans 12 % des cas, une reaction du greffon contre l’hote apres allogreffe pour leucemie aigue myeloide, la presence d’anticorps specifiques du donneur apres transplantation pulmonaire, une microangiopathie thrombotique associee a un cancer, une maladie de Kawaski et une injection dans le cadre d’un essai experimental. Un seul patient avait un antecedent d’insuffisance cardiaque. Le TRALI debutait dans 41 % des cas lors de l’injection d’IgIV et dans 59 % des cas apres la fin de la perfusion. Differents dosages (de 0,4 g/kg a 2 g/kg) et types d’IgIV etaient utilises. En dehors de la detresse respiratoire, les autres symptomes etaient un etat de choc (33 %), de la fievre (18 %), une toux (18 %), des nausees/vomissements (18 %), des frissons (12 %) et une agitation (12 %). L’ETT etait normale dans 82 % des cas. 53 % des patients ont ete ventiles de maniere invasive avec une duree mediane de 1 jour. Les traitements instaures etaient des diuretiques dans la moitie des cas (inefficaces dans 55 % des cas), des corticoides (29 %) et des echanges plasmatiques dans un cas. 4 patients sont decedes. Discussion Bien que cet effet secondaire soit rare (moins de 0,5 % des injections), les cliniciens doivent etre sensibilises a cette complication potentiellement severe. Recemment, certains facteurs de risque ont ete decrits : transfusions massives chez des patients de reanimation, sepsis, pathologie hematologique, insuffisance hepatique ou chirurgie cardiaque [3] . Dans notre serie, la frequence d’une pathologie auto-immune sous-jacente pourrait suggerer l’importance d’un etat pro-inflammatoire preexistant. Conclusion Compte tenu de l’utilisation croissante des IgIV dans differentes pathologies, le clinicien doit evoquer le TRALI en cas de survenue d’une insuffisance respiratoire aigue chez un patient recevant des IgIV.

Sepsis-induced immune dysfunctions are likely to impact on malignant tumor growth. Sequential sepsis-then-cancer models of tumor transplantation in mice recovering from sepsis have shown that the post-septic immunosuppressive environment was able to promote tumor growth. We herein addressed the impact of sepsis on pre-established malignancy in a reverse cancer-then sepsis experimental model. Mice previously inoculated with MCA205 fibrosarcoma cells were subjected to septic challenges by polymicrobial peritonitis induced by cecal ligation and puncture or endotoxinic shock. The anti-tumoral immune response was assessed through the distribution of tumor-infiltrating immune cells, as well as the functions of cytotoxic cells. As compared to sham surgery, polymicrobial sepsis dampened malignant tumor growth in wild-type (WT) mice, but neither in Toll-like receptor 4 (Tlr4)(−/-) nor in Myd88(−/-) mice. Similar tumor growth inhibition was observed following a LPS challenge in WT mice, suggesting a regulatory role of Tlr4 in this setting. The low expression of MHC class 1 onto MCA205 cells suggested the involvement of Natural Killer (NK) cells in sepsis-induced tumor inhibition. Septic insults applied to mice with cancer promoted the main anti-tumoral NK functions of IFNγ production and degranulation. The anti-tumoral properties of NK cells obtained from septic mice were exacerbated when cultured with MHC1(low) MCA205 or YAC-1 cells. These results suggest that sepsis may harbor dual effects on tumor growth depending on the sequential experimental model. When applied in mice with cancer, sepsis prevents tumor growth in a Tlr4-dependent manner by enhancing the anti-tumoral functions of NK cells.

Introduction La thrombolyse a revolutionne le pronostic de l’accident vasculaire cerebral ischemique (AVC). L’angiœdeme (AO) est une complication rare mais potentiellement letale de la thrombolyse. L’incidence de ces AO est variable en fonction des etudes, variant de 1,3 a 7,9 % [1] . Ces donnees sont issues d’etudes retrospectives avec des effectifs faibles et leurs resultats sont parfois contradictoires. Patients et methodes Il s’agit d’une etude retrospective nationale multicentrique. Cent vingt-sept unites neurovasculaires (UNV) ont ete contactees par mail. Les caracteristiques demographiques et les donnees cliniques de ces patients ont ete recueillies. L’AO bradykiniques etait defini par la survenue apres la thrombolyse d’un œdeme non provoque de la langue, des levres ou de l’oropharynx. L’AO etait attribue a la thrombolyse lorsqu’il succedait a l’initiation de ce traitement et lorsqu’il n’avait pas les caracteristiques d’un AO histaminique. Resultats Soixante-treize reponses ont ete obtenues (57,5 % des UNV). Vingt centres ont pu retrouver 43 cas qui ont ete analyses. L’AO post-thrombolyse etait plus frequemment retrouve chez des femmes (55,8 % des cas). La moyenne d’âge etait de 73 ans et les patients etaient d’origine europeenne. Dans 3 cas (0,07 %), il existait un antecedent personnel d’AO bradykinique. Des antecedents d’allergie etaient retrouves dans 0,07 % des cas. Il s’agissait du premier episode d’AVC dans 79 % des cas. Un diabete etait rapporte dans 20,9 % des cas avec un traitement par gliptine chez 3 patients (0,07 %). Parmi les patients, 81,4 % etaient hypertendus. Sur les 43 patients, 29 (67,4 %) etaient traites par IEC (principalement perindopril [41,4 %] et ramipril [27,6 %]), 2 par sartan (0,05 %) et 13 (30,2 %) par betabloquants (en majorite du bisoprolol dans 69,2 % des cas). L’AVC concernait le territoire sylvien dans 90,7 % des cas sans predominance droite ou gauche. Le NIHSS etait en moyenne a 11. Le delai moyen entre l’AVC et la thrombolyse etait de 166,6 min. L’AO survenait en moyenne 115,4 min apres le debut de la thrombolyse et la duree moyenne rapportee de l’episode etait de 21,2 h. Dans 18 cas (41,9 %), il concernait uniquement la langue, dans 8 cas (18,6 %) uniquement les levres et dans 9 cas (20,9 %) la levre et la langue. Dans 2 cas (0,05 %), il existait un œdeme du pharynx qui etait associe a un œdeme de la levre pour un cas et un œdeme de la levre et de la langue pour l’autre cas. Dans 4 cas une atteinte du visage etait rapportee (0,09 %) associe dans 2 cas a une atteinte labiale. Dans les autres cas nous ne disposions pas de la localisation. Lorsque cette donnee etait rapportee (79 % des cas), l’AO etait asymetrique dans la majorite des cas (64,7 %) et etait preferentiellement ipsilateral au deficit (controlateral a la localisation de l’AVC) dans 81,8 % des cas. Douze patients (27,9 %) ont ete hospitalises en reanimation et 4 patients (0,09 %) ont ete intubes et ventiles mecaniquement. Aucune necessite de tracheotomie n’a ete relevee. Deux deces (0,05 %) etaient rapportes a j15 et j19 et non lies a l’AO. Trente-trois patients ont recu des corticoides par voie veineuse (76,7 %), 23 des antihistaminiques (53,5 %) et 6 de l’adrenaline par voie veineuse (14,0 %). Dix patients (23,2 %) ont beneficie d’un traitement specifique par icatibant (50 % des cas) ou concentre de C1 inhibiteur (50 % des cas). Dans 1 cas (0,02 %) de l’acide tranexamique a ete introduit. Six patients n’ont recu aucun traitement (14,0 %). Les IEC ont ete poursuivis apres la sortie chez 10 patients (23,2 %) et introduits pendant l’hospitalisation chez 4 patients (0,09 %). Discussion Cette analyse, sur un effectif superieur aux etudes precedemment rapportees, suggere un lien entre IEC et AO post-thrombolyse ce qui n’avait pas ete retrouve dans une meta-analyse [1] mais etait deja souligne par plusieurs etudes retrospectives [2] , [3] . Elle confirme que l’AO est le plus souvent ipsilateral au deficit et majoritairement peu severe avec cependant possibilite d’engager le pronostic vital [2] . Conformement a la litterature, les corticoides et les antihistaminiques sont le plus souvent utilises malgre leur inefficacite sur cet AO bradykinique et un traitement specifique n’est introduit que dans 23,2 % des cas. Conclusion L’AO est une complication potentiellement dangereuse de la thrombolyse et les IEC sont un facteur de risque. Sa reconnaissance precoce et l’information des neurologues pourraient permettre d’initier rapidement un traitement specifique. Une etude prospective est necessaire afin de mieux connaitre son incidence et ses caracteristiques clinicobiologiques.

Objectives Ventilator-associated pneumonia is frequent in ICUs. Extended-spectrum β-lactamase-producing Enterobacteriaceae are difficult-to-treat pathogens likely to cause ventilator-associated pneumonia. We sought to assess the interest of screening for extended-spectrum β-lactamase-producing Enterobacteriaceae rectal carriage as a way to predict their involvement in ventilator-associated pneumonia. Design A retrospective cohort study of patients with suspected ventilator-associated pneumonia in a medical ICU was conducted. Patients Every patient admitted between January 2006 and August 2013 was eligible if subjected to mechanical ventilation for more than 48 hours. Each patient with suspected ventilator-associated pneumonia was included in the cohort. Active surveillance culture for extended-spectrum β-lactamase-producing Enterobacteriaceae detection was routinely performed in all patients at admission and then weekly throughout the study period. Extended-spectrum β-lactamase colonization was defined by the isolation of at least one extended-spectrum β-lactamase-producing Enterobacteriaceae from rectal swab culture. Interventions None. Measurements and main results Among 587 patients with suspected ventilator-associated pneumonia, 40 (6.8%) were colonized with extended-spectrum β-lactamase-producing Enterobacteriaceae prior to the development of pneumonia. Over the study period, 20 patients (3.4%) had ventilator-associated pneumonia caused by extended-spectrum β-lactamase-producing Enterobacteriaceae; of whom, 17 were previously detected as being colonized with extended-spectrum β-lactamase-producing Enterobacteriaceae. Sensitivity and specificity of prior extended-spectrum β-lactamase-producing Enterobacteriaceae colonization as a predictor of extended-spectrum β-lactamase-producing Enterobacteriaceae involvement in ventilator-associated pneumonia were 85.0% and 95.7%, respectively. The positive and negative predictive values were 41.5% and 99.4%, respectively. The positive likelihood ratio was 19.8. Conclusions Screening for extended-spectrum β-lactamase-producing Enterobacteriaceae digestive colonization by weekly active surveillance cultures could reliably exclude the risk of the involvement of such pathogens in patients with ventilator-associated pneumonia in low-prevalence area.

Equipe EA MERS; International audience; Background : Invasive candidiasis (IC) is a life-threatening ICU-acquired infection. A strong correlation between time to antifungal therapy (AFT) administration and outcome has been established. Empirical therapy benefit should be balanced with the risk of echinocandin overuse. We assessed therefore a decision rule that aimed at guiding empirical therapy. Methods: A 45 month prospective cohort study in a teaching medical ICU. All of the patients with suspected IC (uncontrolled sepsis despite broad spectrum antibiotics without any bacterial proven infection in patients with Candida score >= 3 points including multifocal Candida sp. colonization) were eligible. The primary endpoint was proven IC diagnosis (i.e., candidemia) following treatment onset. Timing of AFT administration was also investigated in those latter patients. Antifungal therapy step-down and discontinuation was done according to international guidelines in patients with candidemia. Otherwise, echinocandin discontinuation was encouraged in patients without proven IC, excepting when a clinical improvement was achieved without any other explanation that antifungals initiation (i.e., probable IC). In addition, a survival multivariate analysis using a Cox model was conducted. Results: Fifty-one patients were given an echinocandin with respect to our decision rule. Among them, candidemia was diagnosed thereafter in 9 patients. Over the same period, antifungal therapy was triggered by candidemia announcement (i.e., definite therapy) in 12 patients who did not fulfill criteria for empirical therapy before. Time elapsed from candidemia onset to echinocandin therapy initiation was shortened (0.4 [0.5] vs. 2.4 [2.8] hours; p = 0.04) when it was given empirically. In addition, 18 patients clinically improved under empirical antifungal therapy without any obvious other explanation, despite IC remained unproven. Moreover, echinocandin exposure duration was independently related to survival in those patients. Over the same period, our predefined criteria for empirical therapy were overruled in 55 cases. None of them develop IC thereafter. Finally, Our decision rule allowed IC early recognition of proven/probable IC with sensitivity, specificity, positive and negative predictive value of 69.2%, 82.1%, 69.2% and 82.1%, respectively. Conclusion: Implementation of pragmatic guidelines for empirical AFT based on CS and fungal colonization assessment could be useful in selecting patients who really benefit from an echinocandin.

Introduction Le transfusion-related acute lung injury (TRALI) est une complication rare mais grave survenant apres transfusion [1] , et est la premiere cause de morbi-mortalite dans les suites d’une transfusion. Son incidence est estimee a environ 8 % en unite de soins intensifs [2] . Une etude a montre une incidence de 0,81 pour 10 000 unites transfusees dans 2 centres medicaux tertiaires en 2009 [3] . Il est generalement de bon pronostic et sa mortalite est estimee a 5 a 10 %. Il est defini par l’apparition dans les 6 heures apres la transfusion de criteres compatibles avec la definition de l’acute lung injury (ALI). Des TRALIs ont ete decrits apres la perfusion de nombreux composants du sang : sang total, culots globulaires rouges (CGR), plaquettes, granulocytes et plasma frais. Les facteurs de risque sont : la ventilation mecanique, les transfusions massives, l’etat de choc, un bilan entree-sortie positif, l’alcoolisme chronique, les hepatopathies severes et un taux eleve d’interleukine-8 avant transfusions. Les facteurs de risque transfusionnels sont le plasma ou le sang total provenant d’un donneur de sexe feminin, le volume d’anticorps anti-HLA de classe II et le volume d’anticorps anti-human neutrophil antigen (HNA). Le traitement est uniquement symptomatique, et la ventilation mecanique est necessaire dans 70 a 90 % des cas. Nous rapportons le cas d’un TRALI survenant au cours d’une perfusion d’immunoglobulines intraveineuses (IgIV). Observation Un homme de 54 ans sans antecedents particuliers consultait aux urgences pour des gingivorragies avec des bulles hemorragiques intra-buccales. Le bilan biologique revelait une thrombopenie a 3000/mm3 sans anomalies des autres lignees. Les bilans immunologique et virologique etaient negatifs. Le myelogramme retrouvait une moelle riche, granuleuse avec de nombreux megacaryocytes. Le diagnostic de purpura thrombopenique immunologique (PTI) etait pose. Un traitement par IgIV etait introduit a la posologie de 1 g/kg/j en association avec la corticotherapie. Apres 50 g d’IgIV, 4 heures apres la fin de la perfusion, on notait l’apparition d’une detresse respiratoire aigue avec desaturation a 80 % sous 15 L/min, tachypnee et hypoxemie a 51 mmHg, justifiant le transfert en reanimation. Le patient etait intube et ventile avec un rapport PaO2/FiO2 initialement inferieur a 300. La radiographie pulmonaire objectivait des opacites alveolo-interstitielles diffues bilaterales. L’echocardiographie etait normale et le lavage broncho-alveolaire ne retrouvait pas de germes. L’evolution etait tres rapidement favorable avec extubation a j3, et normalisation du taux de plaquettes sous corticotherapie. La radiographie realisee a la sortie du patient ne montrait plus d’anomalies parenchymateuses. Le bilan retrouvait des anticorps anti-HLA. Discussion Les IgIV sont des produits derives du sang fabriquees a partir du plasma de plusieurs centaines de donneurs et sont utilisees dans de nombreuses maladies auto-immunes. Seuls quelques cas de TRALIs suite a l’administration d’IgIV ont ete rapportes. Suassuna et al. ont decrit le premier cas avec une exacerbation de syndrome hemolytique et uremique apres IgIV avec symptomatologie ressemblant a un TRALI, sans preuve biologique. Dans seulement deux cas une preuve biologique etait obtenu. Un deces a ete rapporte par Dooren et al. Conclusion Les perfusions d’IgIV peuvent etre responsable exceptionnellement de TRALIs particulierement severes. Le clinicien doit connaitre ce risque pour pouvoir l’evoquer en cas de detresse respiratoire chez un patient en cours de traitement par IgIV. Le traitement est uniquement symptomatique.

Given the high mortality attributable to invasive candidiasis (IC) and the lack of reliable diagnosis tool, antifungals are often started in high-risk patients with severe sepsis despite the absence of proven disease. According to current guidelines, echinocandins are the drugs of choice in this setting. However, the level of evidence supporting this statement is low.

Introduction Ventilator-associated pneumonia (VAP) is the most commonly acquired infection in intensive care units (ICU). Its outcome is related, at least in part, to the host’s response. Statins have anti-inflammatory effects and may thus improve the outcome. We aimed to assess the impact of prior statin use in the setting of VAP. Methods A six-year cohort study was conducted in a French ICU at a teaching hospital. All of the patients with suspected VAP were included. Baseline characteristics, outcomes, statin exposure, and the description of suspected episodes were collected prospectively. The primary endpoint was 30-day mortality. Patients who were taking statins before admission to the ICU whether or not treatment was continued thereafter (‘previous users’ group) were compared to those without prior statin therapy (‘statin-naive’ group). A survival analysis using a Cox model was conducted in the whole cohort and in the subgroup of prior statin users. Results Among the 349 patients included, 93 (26.6%) had taken statins. At baseline, these patients were at higher risk of complications than statin-naive ones (for example, older, more likely to be men and to have underlying diseases, greater simplified acute physiology score II (SAPS II)). There was, however, no difference regarding severity at the time VAP was suspected (sequential organ failure assessment (SOFA): 9.0 (4.0 to 16.0) versus 8.0 (4.0 to 17.0); P = 0.11). Nonetheless, 30-day mortality in statin users was not different from that in statin-naive patients (35.5% versus 26.2%, respectively; adjusted hazard ratio (HR) = 1.23 (0.79 to 1.90) 95% confidence interval (CI); P = 0.36). In contrast, after limiting analysis to prior statin users and adjusting for potential confounders, those who continued the treatment had better survival than those who did not (HR = 0.47; (0.22 to 0.97) 95% CI; P = 0.04). Conclusions Statin continuation in prior users could provide protective effects in patients with suspected VAP.