Alterations of the iNKT cell compartment in brain-injured patients

Karim Asehnoune and Jacques Le Pendu contributed equally to this work.International audienceBACKGROUND:Brain injury (BI) induces a state of immunodepression leading to pneumonia. We investigated the invariant natural killer T (iNKT) cell compartment.METHODS:This is an observational study in two surgical intensive care units (ICUs) of a single institution and a research laboratory. Clinical data and samples from a prospective cohort were extracted. Severe brain-injured patients (n = 33) and sex- and age-matched healthy donors (n = 40) were studied.RESULTS:We observed the presence of IL-10 in serum, a loss of IFN-γ and IL-13 production by peripheral blood mononuclear cells (PBMCs) following IL-2 stimulation, and downregulation of HLA-DR expression on both monocytes and B cells early after BI. Inversely, CD1d, the HLA class I-like molecule involved in antigen presentation to iNKT cells, was over-expressed on patients' monocytes and B cells. The antigen-presenting activity to iNKT cells of PBMCs was increased in the patients who developed pneumonia, but not in those who remained free of infection. Frequencies of iNKT cells among PBMCs were dramatically decreased in patients regardless of their infection status. Following amplification, an increased frequency of CD4+ iNKT cells producing IL-4 was noticed in the group of patients free of infection compared with those who became infected and with healthy donors. Finally, serum from BI patients inhibited the iNKT cells' specific response as well as the non-specific IL-2 stimulation of PBMCs, and the expression of the beta-2 adrenergic receptor was elevated at the surface of patients T lymphocytes.CONCLUSIONS:We observed severe alterations of the iNKT cell compartment, including the presence of inhibitory serum factors. We demonstrate for the first time that the decreased capacity to present antigens is not a generalized phenomenon because whereas the expression of HLA-DR molecules is decreased, the capacity for presenting glycolipids through CD1d expression is higher in patients

High-flow Nasal Cannulae Versus Non-invasive Ventilation for Preoxygenation of Obese Patients: The PREOPTIPOP Randomized Trial

International audienceIn obese patients, preoxygenation with non-invasive ventilation (NIV) was reported to improve outcomes compared with facemask. In this setting, high-flow nasal cannulae (HFNC) used before and during intubation has never been studied against NIV

High-Flow Therapy by Nasal Cannulae Versus High-Flow Face Mask in Severe Hypoxemia After Cardiac Surgery: A Single-Center Randomized Controlled Study-The HEART FLOW Study

International audienceOBJECTIVE: To determine whether high-flow oxygen therapy by nasal cannulae (HFNC) is more effective than a high-flow face mask (HFFM) in severe hypoxemia. DESIGN: Randomized, single-center, open-labeled, controlled trial. SETTING: University Hospital of Nantes, France. PARTICIPANTS: Cardiac surgery patients presenting oxygen saturation <96% with Venturi mask 50%. INTERVENTION: Oxygenation by HFNC (45 L/min, FIO2 100%) or Hudson RCI non-rebreather face mask with a reservoir bag (15 L/min). MEASUREMENTS AND MAIN RESULTS: The co-primary outcomes were the PaO2/FIO2 ratio at 1 and 24 hours. In the intent-to-treat analysis (90 patients), the mean (standard deviation) PaO2/FIO2 ratios were: after 1 hour, 113.4 (50.2) in HFFM versus 137.8 (57.0) in HFNC (mean difference 24.4, CI 97.5% [2.9-45.9], p = 0.03), and after 24 hours, 106.9 (62.6) in HFFM versus 129.9 (54.0) in HFNC (mean difference 23.0, CI 97.5% [1.5-44.6], p = 0.04). After adjustment on baseline PaO2/FIO2, this difference persisted at 24 hours (p = 0.04). For secondary outcomes, the PaO2/FIO2 ratio after 6 hours was 108.7 (47.9) in HFFM versus 136.0 (45.2) in HFNC (p = 0.01), without difference after 48 hours (p = 0.95). Refractory hypoxemia requiring noninvasive ventilation occurred in 13 (28%) patients in HFNC versus 24 (56%) patients in HFFM (p = 0.007). The HFNC improved satisfaction (p = 0.0002) and reduced mucus dryness (p = 0.003) compared with HFFM. CONCLUSION: In patients with severe hypoxemia after cardiac surgery, PaO2/FIO2 at 1 and 24 hours were higher and the use of noninvasive ventilation was reduced in HFNC compared with HFFM

Romiplostim as a Transfusion Saving Strategy in 20 Patients after Heart or Lung Transplantation: A Single Centre before-after Pilot Study

International audienceBACKGROUND: Thrombocytopenia is a common disorder after heart or lung transplantation. Platelet transfusion is often required to maintain haemostasis but represents a specific cause of morbidity and mortality in this setting including alloimmunisation and graft rejection. STUDY DESIGN AND METHODS: As part of a health-care quality improvement project, in a single-centre before-after pilot study, the relevance of a platelet transfusion saving strategy based on romiplostim administration after transplantation was assessed in patients with platelet count <100\,\texttimes\,109/L. Transfusions on days 28 and 90 were compared using propensity matched score for adjustment of demographic characteristics at baseline. The primary outcome was platelet transfusion until day 28 after transplantation. RESULTS: Ninety-three patients were analysed (73 before vs. 20 after). The median [interquartile range] number of platelet concentrate was 1 [0;4.0] before versus 0.5 [0;2.0] in the after period, mean difference 0.5 confidence interval 95% [-0.7 to 1.7], p\,=\,0.39. On day 28, median [interquartile range] red blood cell transfusion was significantly higher in the before versus the after period, 7 [2.0;13.5] versus 6 [1.5;8.5], mean difference 3.2 CI 95% [0.4-6.0], p\,=\,0.02. At 6\,months, the rate of patients with de novo anti-human leukocyte antigen alloimmunisation was 45% before versus 53% in the after period (p\,=\,0.56). Deep venous thrombosis was detected in nine patients (12%) before versus seven patients (35%) in the after period (p\,=\,0.04). CONCLUSION: Romiplostim did not significantly reduce platelet transfusion after heart or lung transplantation. Its relevance and safety in a global transfusion strategy remains to be studied in this setting in a large randomised study

Pseudomonas aeruginosa Infection Impairs NKG2D-Dependent NK Cell Cytotoxicity through Regulatory T-Cell Activation

International audienceNatural killer (NK) cells play a key role in both antibacterial and antitumor immunity. Pseudomonas aeruginosa infection has already been reported to alter NK cell functions. We studied in vitro the effect of P. aeruginosa on NK cell cytotoxic response (CD107a membrane expression) to a lymphoma cell line. Through positive and negative cell sorting and adoptive transfer, we determined the influence of monocytes, lymphocytes, and regulatory T cells (Treg) on NK cell function during P. aeruginosa infection. We also studied the role of the activating receptor natural killer group 2D (NKG2D) in NK cell response to B221. We determined that P. aeruginosa significantly altered both cytotoxic response to B221 and NKG2D expression on NK cells in a Treg-dependent manner and that the NKG2D receptor was involved in NK cell cytotoxic response to B221. Our results also suggested that during P. aeruginosa infection, monocytes participated in Treg-mediated NK cell alteration. In conclusion, P. aeruginosa infection impairs NK cell cytotoxicity and alters antitumor immunity. These results highlight the strong interaction between bacterial infection and immunity against cancer

Preoxygenation in difficult airway management: high-flow oxygenation by nasal cannula versus face mask (the PREOPTIDAM study). Protocol for a single-centre randomised study

International audienceAlthough preoxygenation and airway management respond to precise algorithms, difficult intubation (DI) remains a daily challenge in intensive care units and in the operating rooms because of its frequent complications, including hypoxaemia. To prevent desaturation during DI, high-flow oxygenation by nasal cannula (HFNC) could prove beneficial. Indeed, contrary to standard preoxygenation device, it can be held in place throughout the intubation trying to perform apnoeic oxygenation during DI. Hence, recent guidelines recommend HFNC during DI, but its relevance has never been evaluated in this setting in a large randomised study until now

Prevalence, Characteristics, and Outcomes of COVID-19-Associated Acute Myocarditis

Background: Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19-associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe. Methods: A total of 112 patients with suspected AM from 56 963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19-associated AM. Results: AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19-associated pneumonia. Twenty-one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia (P=0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47; P&lt;0.0001) similarly in patients with or without pneumonia. Corticosteroids were frequently administered (55.5%). Conclusions: AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia