Search

Bronchiolitis obliterans syndrome (BOS), the main manifestation of chronic lung allograft dysfunction, leads to poor long-term survival after lung transplantation. Identifying predictors of BOS is essential to prevent the progression of dysfunction before irreversible damage occurs. By using a large set of 107 samples from lung recipients, we performed microarray gene expression profiling of whole blood to identify early biomarkers of BOS, including samples from 49 patients with stable function for at least 3 years, 32 samples collected at least 6 months before BOS diagnosis (prediction group), and 26 samples at or after BOS diagnosis (diagnosis group). An independent set from 25 lung recipients was used for validation by quantitative PCR (13 stables, 11 in the prediction group, and 8 in the diagnosis group). We identified 50 transcripts differentially expressed between stable and BOS recipients. Three genes, namely POU class 2 associating factor 1 (POU2AF1), T-cell leukemia/lymphoma protein 1A (TCL1A), and B cell lymphocyte kinase, were validated as predictive biomarkers of BOS more than 6 months before diagnosis, with areas under the curve of 0.83, 0.77, and 0.78 respectively. These genes allow stratification based on BOS risk (log-rank test p

Background: The development of controlled donation after circulatory death (cDCD) is both important and challenging. The tension between end-of-life care and organ donation raises significant ethical issues for healthcare professionals in the intensive care unit (ICU). The aim of this prospective, multicenter, observational study is to better understand ICU physicians' and nurses' experiences with cDCD., Methods: In 32 ICUs in France, ICU physicians and nurses were invited to complete a questionnaire after the death of end-of-life ICU patients identified as potential cDCD donors who had either experienced the withdrawal of life-sustaining therapies alone or with planned organ donation (OD(-) and OD( +) groups). The primary objective was to assess their anxiety (State Anxiety Inventory STAI Y-A) following the death of a potential cDCD donor. Secondary objectives were to explore potential tensions experienced between end-of-life care and organ donation., Results: Two hundred six ICU healthcare professionals (79 physicians and 127 nurses) were included in the course of 79 potential cDCD donor situations. STAI Y-A did not differ between the OD(-) and OD( +) groups for either physicians or nurses (STAI Y-A were 34 (27-38) in OD(-) vs. 32 (27-40) in OD( +), p = 0.911, for physicians and 32 (25-37) in OD(-) vs. 39 (26-37) in OD( +), p = 0.875, for nurses). The possibility of organ donation was a factor influencing the WLST decision for nurses only, and a factor influencing the WLST implementation for both nurses and physicians. cDCD experience is perceived positively by ICU healthcare professionals overall., Conclusions: cDCD does not increase anxiety in ICU healthcare professionals compared to other situations of WLST. WLST and cDCD procedures could further be improved by supporting professionals in making their intentions clear between end-of-life support and the success of organ donation, and when needed, by enhancing communication between ICU physician and nurses., Trial Registration: This research was registered in ClinicalTrials.gov (Identifier: NCT05041023, September 10, 2021)., (© 2024. The Author(s).)

Background: Cardiac arrest is the most life-threatening complication of attempted suicide by hanging. However, data are scarce on its characteristics and outcome predictors., Methods: This retrospective observational multicentre study in 31 hospitals included consecutive adults admitted after cardiac arrest induced by suicidal hanging. Factors associated with in-hospital mortality were identified by multivariate logistic regression with multiple imputations for missing data and adjusted to the temporal trends over the study period., Results: Of 450 patients (350 men, median age, 43 [34-52] years), 305 (68%) had a psychiatric history, and 31 (6.9%) attempted hanging while hospitalized. The median time from unhanging to cardiopulmonary resuscitation was 0 [0-5] min, and the median time to return of spontaneous circulation (ROSC) was 20 [10-30] min. Seventy-nine (18%) patients survived to hospital discharge. Three variables were independently associated with higher in-hospital mortality: time from collapse or unhanging to ROSC>20 min (odds ratio [OR], 4.71; 95% confidence intervals [95%CIs], 2.02-10.96; p = 0.0004); glycaemia >1.4 g/L at admission (OR, 6.38; 95%CI, 2.60-15.66; p < 0.0001); and lactate >3.5 mmol/L at admission (OR, 6.08; 95%CI, 1.71-21.06; p = 0.005). A Glasgow Coma Scale (GCS) score of >5 at admission was associated with lower in-hospital mortality (OR, 0.009; 95%CI, 0.02-0.37; p = 0.0009)., Conclusion: In patients with hanging-induced cardiac arrest, time from collapse or unhanging to return of spontaneous circulation, glycaemia, arterial lactate, and coma depth at admission were independently associated with survival to hospital discharge. Knowledge of these risk factors may help guide treatment decisions in these patients at high risk of hospital mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Salvetti, Schnell, Pichon, Schenck, Cronier, Perbet, Lascarrou, Guitton, Lesieur, Argaud, Colin, Cholley, Quenot, Merdji, Geeraerts, Piagnerelli, Jacq, Paul, Chelly, de Charentenay, Deye, Danguy des Déserts, Thiery, Simon, Das, Jacobs, Cerf, Mayaux, Beuret, Ouchenir, Lafarge, Sauneuf, Daubin, Cariou, Silva and Legriel.)

Lung transplantation is limited by the shortage of suitable donors. Many programs have begun to use extended criteria donors. Donors over 65 years old are rarely reported, especially for young cystic fibrosis recipients. This monocentric study was conducted for cystic fibrosis recipients from January 2005 to December 2019, comparing two cohorts according to lung donor age (<65 years or ≥65 years). The primary objective was to assess the survival rate at 3 years using a Cox multivariable model. Of the 356 lung recipients, 326 had donors under 65 years, and 30 had donors over 65 years. Donors' characteristics did not differ significantly in terms of sex, time on mechanical ventilation before retrieval, and partial pressure of arterial oxygen/fraction of inspired oxygen ratio. There were no significant differences in post-operative mechanical ventilation duration and incidence of grade 3 primary graft dysfunction between the two groups. At 1, 3, and 5 years, the percentage of predicted forced expiratory volume in 1 s ( p = 0.767) and survival rate did not differ between groups ( p = 0.924). The use of lungs from donors over 65 years for cystic fibrosis recipients allows extension of the donor pool without compromising results. Longer follow-up is needed to assess the long-term effects of this practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Glorion, Sarsam, Roux, Stern, Belousova, Fessler, Pricopi, De Wolf, Picard, Brugière, De Miranda, Grenet, Tachon, Cerf, Parquin, Le Guen, Chapelier, Vallée and Sage.)

Introduction: Corticosteroids affect variably survival in sepsis trials, suggesting heterogeneity in patients' response to corticosteroids. The RECORDS (Rapid rEcognition of COrticosteRoiD resistant or sensitive Sepsis) trial aimed at defining endotypes associated with adults with sepsis responsiveness to corticosteroids., Methods and Analysis: RECORDS, a multicentre, placebo-controlled, biomarker-guided, adaptive Bayesian design basket trial, will randomly assign to a biomarker stratum 1800 adults with community-acquired pneumonia, vasopressor-dependent sepsis, septic shock or acute respiratory distress syndrome. In each stratum, patients will be randomly assigned to receive a 7-day course of hydrocortisone and fludrocortisone or their placebos. Patients with COVID-19 will be treated with a 10-day standard course of dexamethasone and randomised to fludrocortisone or its placebo. Primary outcome will be 90-day death or persistent organ dysfunction. Large simulation study will be performed across a range of plausible scenarios to foresee power to detect a 5%-10% absolute difference with corticosteroids. We will assess subset-by-treatment interaction by estimating in a Bayesian framework two quantities: (1) measure of influence, relying on the value of the estimation of corticosteroids' effect in each subset, and (2) measure of interaction., Ethics and Dissemination: The protocol was approved by the Ethics Committee ( Comité de Protection des Personnes, Dijon, France), on 6 April 2020. Trial results will be disseminated at scientific conferences and results will be published in peer-reviewed journals., Trial Registration Number: ClinicalTrials.gov Registry (NCT04280497)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Although eosinophil-induced manifestations can be life-threatening, studies focusing on the epidemiology and clinical manifestations of eosinophilia in the intensive care unit (ICU) are lacking., Methods: A retrospective, national, multicenter (14 centers) cohort study over 6 years of adult patients who presented with eosinophilia ≥ 1 × 10 9 /L on two blood samples performed from the day before admission to the last day of an ICU stay., Results: 620 patients (0.9% of all ICU hospitalizations) were included: 40% with early eosinophilia (within the first 24 h of ICU admission, ICU-Eo1 group) and 56% with delayed (> 24 h after ICU admission, ICU-Eo2 group) eosinophilia. In ICU-Eo1, eosinophilia was mostly due to respiratory (14.9%) and hematological (25.8%) conditions, frequently symptomatic (58.1%, mainly respiratory and cardiovascular manifestations) requiring systemic corticosteroids in 32.2% of cases. In ICU-Eo2, eosinophil-related organ involvement was rare (25%), and eosinophilia was mostly drug-induced (46.8%). Survival rates at day 60 (D60) after ICU admission were 21.4% and 17.2% (p = 0.219) in ICU-Eo1 and ICU-Eo2 patients, respectively. For ICU-Eo1 patients, in multivariate analysis, risk factors for death at D60 were current immunosuppressant therapy at ICU admission, eosinophilia of onco-hematological origin and the use of vasopressors at ICU admission, whereas older age and the use of vasopressors or mechanical ventilation at the onset of eosinophilia were associated with a poorer prognosis for ICU-Eo2 patients., Conclusion: Eosinophilia ≥ 1 × 10 9 /L is not uncommon in the ICU. According to the timing of eosinophilia, two subsets of patients requiring different etiological workups and management can be distinguished., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Ventilator-associated pneumonia (VAP) incidence is high among critically ill COVID-19 patients. Its attributable mortality remains underestimated, especially for unresolved episodes. Indeed, the impact of therapeutic failures and the determinants that potentially affect mortality are poorly evaluated. We assessed the prognosis of VAP in severe COVID-19 cases and the impact of relapse, superinfection, and treatment failure on 60-day mortality. Methods: We evaluated the incidence of VAP in a multicenter prospective cohort that included adult patients with severe COVID-19, who required mechanical ventilation for ≥48 h between March 2020 and June 2021. We investigated the risk factors for 30-day and 60-day mortality, and the factors associated with relapse, superinfection, and treatment failure. Results: Among 1424 patients admitted to eleven centers, 540 were invasively ventilated for 48 h or more, and 231 had VAP episodes, which were caused by Enterobacterales (49.8%), P. aeruginosa (24.8%), and S. aureus (22%). The VAP incidence rate was 45.6/1000 ventilator days, and the cumulative incidence at Day 30 was 60%. VAP increased the duration of mechanical ventilation without modifying the crude 60-day death rate (47.6% vs. 44.7% without VAP) and resulted in a 36% increase in death hazard. Late-onset pneumonia represented 179 episodes (78.2%) and was responsible for a 56% increase in death hazard. The cumulative incidence rates of relapse and superinfection were 45% and 39.5%, respectively, but did not impact death hazard. Superinfection was more frequently related to ECMO and first episode of VAP caused by non-fermenting bacteria. The risk factors for treatment failure were an absence of highly susceptible microorganisms and vasopressor need at VAP onset. Conclusions: The incidence of VAP, mainly late-onset episodes, is high in COVID-19 patients and associated with an increased risk of death, similar to that observed in other mechanically ventilated patients. The high rate of VAP due to difficult-to-treat microorganisms, pharmacokinetic alterations induced by renal replacement therapy, shock, and ECMO likely explains the high cumulative risk of relapse, superinfection, and treatment failure.

Background: Strong evidence suggests a correlation between pharmacodynamics (PD) index and antibiotic efficacy while dose adjustment should be considered in critically ill patients due to modified pharmacokinetic (PK) parameters and/or higher minimum inhibitory concentrations (MICs). This study aimed to assess pharmacodynamic (PD) target attainment considering both antibiotics serum concentrations and measured MICs in these patients. Method: A multicentric prospective open-label trial conducted in 11 French ICUs involved patients with Gram-negative bacilli (GNB) ventilator-associated pneumonia (VAP) confirmed by quantitative cultures. Results: We included 117 patients. Causative GNBs were P. aeruginosa (40%), Enterobacter spp. (23%), E. coli (20%), and Klebsiella spp. (16%). Hence, 117 (100%) patients received β-lactams, 65 (58%) aminoglycosides, and two (1.5%) fluoroquinolones. For β-lactams, 83% of the patients achieved a Cmin/MIC > 1 and 70% had a Cmin/MIC > 4. In the case of high creatinine clearance (CrCL > 100 mL/min/1.73 m2), 70.4% of the patients achieved a Cmin/MIC ratio > 1 versus 91% otherwise (p = 0.041), and 52% achieved a Cmin/MIC ratio > 4 versus 81% (p = 0.018). For aminoglycosides, 94% of the patients had a Cmax/MIC ratio > 8. Neither β-lactams nor aminoglycosides PK/PD parameters were associated clinical outcomes, but our data suggest a correlation between β-lactams Cmin/MIC and microbiological success. Conclusion: In our ICU patients treated for GNB VAP, using recommended antibiotic dosage led in most cases to PK/PD targets attainment for aminoglycosides and β-lactams. High creatinine clearance should encourage clinicians to focus on PK/PD issues.

Importance: The benefit of high-dose dexamethasone and oxygenation strategies vs standard of care for patients with severe acute hypoxemic respiratory failure (AHRF) caused by COVID-19 pneumonia is debated., Objectives: To assess the benefit of high-dose dexamethasone compared with standard of care dexamethasone, and to assess the benefit of high-flow nasal oxygen (HFNo2) or continuous positive airway pressure (CPAP) compared with oxygen support standard of care (o2SC)., Design, Setting, and Participants: This multicenter, placebo-controlled randomized clinical trial was conducted in 19 intensive care units (ICUs) in France from April 2020 to January 2021. Eligible patients were consecutive ICU-admitted adults with COVID-19 AHRF. Randomization used a 2 × 3 factorial design for dexamethasone and oxygenation strategies; patients not eligible for at least 1 oxygenation strategy and/or already receiving invasive mechanical ventilation (IMV) were only randomized for dexamethasone. All patients were followed-up for 60 days. Data were analyzed from May 26 to July 31, 2021., Interventions: Patients received standard dexamethasone (dexamethasone-phosphate 6 mg/d for 10 days [or placebo prior to RECOVERY trial results communication]) or high-dose dexamethasone (dexamethasone-phosphate 20 mg/d on days 1-5 then 10 mg/d on days 6-10). Those not requiring IMV were additionally randomized to o2SC, CPAP, or HFNo2., Main Outcomes and Measures: The main outcomes were time to all-cause mortality, assessed at day 60, for the dexamethasone interventions, and time to IMV requirement, assessed at day 28, for the oxygenation interventions. Differences between intervention groups were calculated using proportional Cox models and expressed as hazard ratios (HRs)., Results: Among 841 screened patients, 546 patients (median [IQR] age, 67.4 [59.3-73.1] years; 414 [75.8%] men) were randomized between standard dexamethasone (276 patients, including 37 patients who received placebo) or high-dose dexamethasone (270 patients). Of these, 333 patients were randomized among o2SC (109 patients, including 56 receiving standard dexamethasone), CPAP (109 patients, including 57 receiving standard dexamethasone), and HFNo2 (115 patients, including 56 receiving standard dexamethasone). There was no difference in 60-day mortality between standard and high-dose dexamethasone groups (HR, 0.96 [95% CI, 0.69-1.33]; P = .79). There was no significant difference for the cumulative incidence of IMV criteria at day 28 among o2 support groups (o2SC vs CPAP: HR, 1.08 [95% CI, 0.71-1.63]; o2SC vs HFNo2: HR, 1.04 [95% CI, 0.69-1.55]) or 60-day mortality (o2SC vs CPAP: HR, 0.97 [95% CI, 0.58-1.61; o2SC vs HFNo2: HR, 0.89 [95% CI, 0.53-1.47]). Interactions between interventions were not significant., Conclusions and Relevance: In this randomized clinical trial among ICU patients with COVID-19-related AHRF, high-dose dexamethasone did not significantly improve 60-day survival. The oxygenation strategies in patients who were not initially receiving IMV did not significantly modify 28-day risk of IMV requirement., Trial Registration: ClinicalTrials.gov Identifier: NCT04344730; EudraCT: 2020-001457-43.

Objective: Many prognostic factors of grade-3 primary graft dysfunction at postoperative day 3 (PGD3-T72) have been reported, but intraoperative blood lactate level has not been studied. The present retrospective study was done to test the hypothesis that intraoperative blood lactate level (BLL) could be a predictor of PGD3-T72 after double-lung transplantation., Design: Retrospective monocentric cohort study., Setting: Foch University Hospital, Suresnes, France., Participants: Patients having received a double-lung transplantation between 2012 and 2019. Patients transplanted twice during the study period, having undergone a multiorgan transplantation, or cardiopulmonary bypass, and those under preoperative extracorporeal membrane oxygenation, were excluded., Interventions: None., Measurements and Main Results: Analysis was performed on a cohort of 449 patients. Seventy-two (16%) patients had a PGD3-T72. Blood lactate level increased throughout surgery to reach a median value of 2.2 (1.6-3.2) mmol/L in the No-PGD3-T72 group and 3.4 (2.3-5.0) mmol/L in the PGD3-T72 group after second lung implantation. The best predictive model for PGD3-T72 was obtained adding a lactate threshold of 2.6 mmol/L at the end of surgery to the clinical model, and the area under the curve was 0.867, with a sensitivity = 76.9% and specificity = 85.4%. Repeated-measures mixed model of BLL during surgery remained significant after adjustment for covariates (F ratio= 4.22, p < 0.001 for interaction)., Conclusions: Blood lactate level increases during surgery and reaches a maximum after the second lung implantation. A value below the threshold of 2.6 mmol/L at the end of surgery has a high negative predictive value for the occurrence of a grade-3 primary graft dysfunction at postoperative day 3., Competing Interests: Conflict of Interest None, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Pre-formed donor-specific antibodies (DSAs) are associated with worse outcome after lung transplantation (LTx) and might limit access to LTx. A virtual crossmatch-based strategy for perioperative desensitisation protocol has been used for immunised LTx candidates since 2012 at Foch Hospital (Suresnes, France). We compared the outcome of desensitised LTx candidates with high DSA mean fluorescence intensity and those with low or no pre-formed DSAs, not desensitised., Methods: For all consecutive LTx recipients (January 2012 to March 2018), freedom from chronic lung allograft dysfunction (CLAD) and graft survival were assessed using Kaplan-Meier analysis and Cox multivariate analysis., Results: We compared outcomes for desensitised patients with high pre-formed DSAs (n=39) and those with no (n=216) or low pre-formed DSAs (n=66). The desensitisation protocol decreased the level of immunodominant DSA (class I/II) at 1, 3 and 6 months post-LTx (p<0.001, p<0.01 and p<0.001, respectively). Freedom from CLAD and graft survival at 3 years was similar in the desensitised group as a whole and other groups. Nevertheless, incidence of CLAD was higher with persistent high-level DSAs than cleared high-level (p=0.044) or no DSAs (p=0.014). Conversely, graft survival was better with cleared high DSAs than persistent high-level, low-level and no pre-formed DSAs (p=0.019, p=0.025 and p=0.044, respectively). On multivariate analysis, graft survival was associated with cleared high DSAs (hazard ratio 0.12, 95% CI 0.02-0.85 versus no DSAs; p=0.035) and CLAD with persistent DSAs (3.04, 1.02-9.17 versus no pre-formed DSAs; p=0.048)., Conclusion: The desensitisation protocol in LTx recipients with high pre-formed DSAs was associated with satisfactory outcome, with cleared high pre-formed DSAs after desensitisation identified as an independent predictor of graft survival., Competing Interests: Conflict of interest: F. Parquin has nothing to disclose. Conflict of interest: B. Zuber has nothing to disclose. Conflict of interest: A. Vallée has nothing to disclose. Conflict of interest: J-L. Taupin has nothing to disclose. Conflict of interest: E. Cuquemelle has nothing to disclose. Conflict of interest: S. Malard has nothing to disclose. Conflict of interest: M. Neuville has nothing to disclose. Conflict of interest: J. Devaquet has nothing to disclose. Conflict of interest: M. Le Guen has nothing to disclose. Conflict of interest: J. Fessler has nothing to disclose. Conflict of interest: L. Beaumont has nothing to disclose. Conflict of interest: C. Picard has nothing to disclose. Conflict of interest: A. Hamid has nothing to disclose. Conflict of interest: S. Colin de Verdière has nothing to disclose. Conflict of interest: D. Grenet has nothing to disclose. Conflict of interest: S. De Miranda has nothing to disclose. Conflict of interest: M. Glorion has nothing to disclose. Conflict of interest: E. Sage has nothing to disclose. Conflict of interest: C. Pricopi has nothing to disclose. Conflict of interest: J. De Wolf has nothing to disclose. Conflict of interest: A-L. Brun has nothing to disclose. Conflict of interest: E. Longchampt has nothing to disclose. Conflict of interest: C. Cerf has nothing to disclose. Conflict of interest: A. Roux has nothing to disclose. Conflict of interest: O. Brugière has nothing to disclose., (Copyright ©The authors 2021. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Rapidly progressive interstitial lung disease (RPILD) associated with the anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5ab+) dermatomyositis (DM) is a rare but life-threatening condition despite immunosuppressive treatment. We report the case of a 44-year-old woman who was diagnosed with severe RPILD associated with anti-MDA5ab+ DM 1 week before her admission in the intensive care unit. The patient underwent a successful double-lung transplant after she failed treatment with immunosuppressive therapy, including tofacitinib. At 1-year follow-up, she had experienced no relapse of the disease., Case Report: This case includes a patient recently diagnosed with RPILD for whom no treatment showed efficacy, including glucocorticoids, cyclophosphamide, plasma exchanges, tofacitinib, and tacrolimus. She was placed under mechanical ventilation and venovenous extracorporeal membrane oxygenation 2 weeks after diagnosis in a bridge-to-transplant process. She was successfully transplanted 20 days later after having been registered on the French National Lung Transplant Waiting List with high priority. One year after surgery, her pulmonary function tests were good, and she showed no sign of relapse of anti-MDA5ab+ DM., Conclusions: Lung transplantation can be a life-saving procedure in RPILD related to anti-MDA5ab+ DM. High-emergency allocation priority on the transplant list reduced the time between diagnosis and surgery. Patients without comorbidities should be promptly referred to specialized centers to rapidly assess the feasibility of transplantation in this context., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Previous studies have unveiled a relationship between the severity of coronavirus disease 2019 (COVID-19) pneumonia and obesity. The aims of this multicenter retrospective cohort study were to disentangle the association of BMI and associated metabolic risk factors (diabetes, hypertension, hyperlipidemia, and current smoking status) in critically ill patients with COVID-19., Methods: Patients admitted to intensive care units for COVID-19 in 21 centers (in Europe, Israel, and the United States) were enrolled in this study between February 19, 2020, and May 19, 2020. Primary and secondary outcomes were the need for invasive mechanical ventilation (IMV) and 28-day mortality, respectively., Results: A total of 1,461 patients were enrolled; the median (interquartile range) age was 64 years (40.9-72.0); 73.2% of patients were male; the median BMI was 28.1 kg/m 2 (25.4-32.3); a total of 1,080 patients (73.9%) required IMV; and the 28-day mortality estimate was 36.1% (95% CI: 33.0-39.5). An adjusted mixed logistic regression model showed a significant linear relationship between BMI and IMV: odds ratio = 1.27 (95% CI: 1.12-1.45) per 5 kg/m 2 . An adjusted Cox proportional hazards regression model showed a significant association between BMI and mortality, which was increased only in obesity class III (≥40; hazard ratio = 1.68 [95% CI: 1.06-2.64])., Conclusions: In critically ill COVID-19 patients, a linear association between BMI and the need for IMV, independent of other metabolic risk factors, and a nonlinear association between BMI and mortality risk were observed., (© 2021 The Obesity Society.)

Background: In the Île-de-France region (henceforth termed Greater Paris), extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS) was considered early in the COVID-19 pandemic. We report ECMO network organisation and outcomes during the first wave of the pandemic., Methods: In this multicentre cohort study, we present an analysis of all adult patients with laboratory-confirmed SARS-CoV-2 infection and severe ARDS requiring ECMO who were admitted to 17 Greater Paris intensive care units between March 8 and June 3, 2020. Central regulation for ECMO indications and pooling of resources were organised for the Greater Paris intensive care units, with six mobile ECMO teams available for the region. Details of complications (including ECMO-related complications, renal replacement therapy, and pulmonary embolism), clinical outcomes, survival status at 90 days after ECMO initiation, and causes of death are reported. Multivariable analysis was used to identify pre-ECMO variables independently associated with 90-day survival after ECMO., Findings: The 302 patients included who underwent ECMO had a median age of 52 years (IQR 45-58) and Simplified Acute Physiology Score-II of 40 (31-56), and 235 (78%) of whom were men. 165 (55%) were transferred after cannulation by a mobile ECMO team. Before ECMO, 285 (94%) patients were prone positioned, median driving pressure was 18 cm H 2 O (14-21), and median ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen was 61 mm Hg (IQR 54-70). During ECMO, 115 (43%) of 270 patients had a major bleeding event, 27 of whom had intracranial haemorrhage; 130 (43%) of 301 patients received renal replacement therapy; and 53 (18%) of 294 had a pulmonary embolism. 138 (46%) patients were alive 90 days after ECMO. The most common causes of death were multiorgan failure (53 [18%] patients) and septic shock (47 [16%] patients). Shorter time between intubation and ECMO (odds ratio 0·91 [95% CI 0·84-0·99] per day decrease), younger age (2·89 [1·41-5·93] for ≤48 years and 2·01 [1·01-3·99] for 49-56 years vs ≥57 years), lower pre-ECMO renal component of the Sequential Organ Failure Assessment score (0·67, 0·55-0·83 per point increase), and treatment in centres managing at least 30 venovenous ECMO cases annually (2·98 [1·46-6·04]) were independently associated with improved 90-day survival. There was no significant difference in survival between patients who had mobile and on-site ECMO initiation., Interpretation: Beyond associations with similar factors to those reported on ECMO for non-COVID-19 ARDS, 90-day survival among ECMO-assisted patients with COVID-19 was strongly associated with a centre's experience in venovenous ECMO during the previous year. Early ECMO management in centres with a high venovenous ECMO case volume should be advocated, by applying centralisation and regulation of ECMO indications, which should also help to prevent a shortage of resources., Funding: None., Competing Interests: Declaration of interests GL reports lecture fees from Livanova and Abiomed, outside of the submitted work. MS reports lecture fees from Getinge, Dräger, and Xenios, outside of the submitted work. BC reports consulting and lecture fees from Edwards Lifesciences, Orion Pharma, Amomed, and Nordic Pharma, outside of the submitted work. RS has received lecture fees from Baxter, outside of the submitted work. DL reports speaker fees and is a member of advisory boards for Edwards Lifesciences, Medtronic, and Masimo, outside of the submitted work. AC reports grants and personal fees from Getinge, and personal fees from Baxter and Xenios, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: A strong COVID-19 vaccine campaign is needed to reach the herd immunity and reduce this pandemic infection., Study Design: In the Foch Hospital, France, in February 2021, 451 healthcare workers were vaccinated by a first dose of AstraZeneca vaccine., Methods: Adverse effects were reported to our pharmaco-vigilance circuit, by an online and anonymous questionnaire following the first weeks of the vaccinal campaign to healthcare workers., Results: Two hundred seventy-four (60.8%) of them reported multiple adverse effects. Main adverse effects reported were feverish state/chills (65.7%), fatigue/physical discomfort (62.4%), arthralgia/muscle pain (61.0%) and fever (44.5%)., Conclusions: On March 2021 many European countries suspended AstraZeneca vaccine for one week due to safety uncertainty. Thus, confidence in its efficacy is undermined. However, the benefit/risk balance is clearly in favor of vaccination., (Copyright © 2021 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: Operating room (OR) extubation has been reported after lung transplantation (LT) in small cohorts. This study aimed to evaluate the prognosis of OR-extubated patients. The secondary objectives were to evaluate the safety of this approach and to identify its predictive factors., Methods: This retrospective single-center cohort study included patients undergoing double lung transplantation (DLT) from January 2012 to June 2019. Patients undergoing multiorgan transplantation, repeat transplantation, or cardiopulmonary bypass during the study period were excluded. OR-extubated patients were compared with intensive care unit (ICU)-extubated patients., Results: Among the 450 patients included in the analysis, 161 (35.8%) were extubated in the OR, and 4 were reintubated within 24 hours. Predictive factors for OR extubation were chronic obstructive pulmonary disease (COPD)/emphysema (p = .002) and cystic fibrosis (p = .005), recipient body mass index (p = .048), and the PaO 2 /FiO 2 ratio 10 minutes after second graft implantation (p < .001). OR-extubated patients had a lower prevalence of grade 3 primary graft dysfunction at day 3 (p < .001). Eight (5.0%) patients died within the first year after OR extubation, and 49 (13.5%) patients died after ICU extubation (log-rank test; p = .005). After adjustment for OR extubation predictive factors, the multivariate Cox regression model showed that OR extubation was associated with greater one-year survival (adjusted hazard ratio = 0.40 [0.16-0.91], p = .028)., Conclusions: OR extubation was associated with a favorable prognosis after DLT, but the association should not be interpreted as causality. This fast-track protocol was made possible by a team committed to developing a comprehensive strategy to enhance recovery., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a poorly understood disease involving a high inflammatory status. Neutrophil extracellular traps (NETs) have been described as a new pathway to contain infectious diseases but can also participate in the imbalance of the inflammatory and the coagulation systems. NETs could be a therapeutic target in COVID-19 patients. Methods: Consecutive patients with SARS-CoV2 related pneumonia admitted to the intensive care unit were included in a prospective bicentric study. Neutrophil extracellular trap concentrations were quantified in whole blood samples at day-1 and day-3 by flow cytometry. The primary outcome was the association between the blood NET quantification at ICU admission and the number of days with refractory hypoxemia defined by a PaO 2 /FIO 2 ratio ≤100 mmHg. Results: Among 181 patients admitted to the ICUs for acute respiratory failure related to SARS-CoV2 pneumonia, 58 were included in the analysis. Patients were 62 [54, 69] years old in median, mostly male (75.9%). The median number of days with severe hypoxemia was 4 [2, 6] days and day-28 mortality was 27.6% ( n = 16). The blood level of NETs significantly decreased between day-1 and day-3 in patients who survived (59.5 [30.5, 116.6] to 47 [33.2, 62.4] p = 0.006; 8.6 [3.4, 18.0] to 4 [1.4, 10.7] p = 0.001 and 7.4 [4.0, 16.7] to 2.6 [1.0, 8.3] p = 0.001 for MPO+, Cit-H3+, and MPO+ Cit-H3+ NETs, respectively) while it remained stable in patients who died (38.4 [26.0, 54.8] to 44.5 [36.4, 77.7] p = 0.542; 4.9 [1.3, 13.0] to 5.5 [2.8, 6.9] p = 0.839 and 4 [1.3, 13.6] to 2.7 [1.4, 4.5] p = 0.421 for MPO+, Cit-H3+, and MPO+ Cit-H3+ NETs, respectively). In multivariable negative binomial regression, the blood level of MPO+ NETs was negatively associated with the number of days with severe hypoxemia within 7 days (0.84 [0.73, 0.97]), while neither Cit-H3+ NETs nor double-positive NETs were significantly associated with the primary outcome. Conclusion: The whole blood level of NETs at day-1 was negatively associated with the number of days with severe hypoxemia in patients admitted to the intensive care unit for SARS-CoV2 related pneumonia. The lack of decrease of the blood level of NETs between day-1 and day-3 discriminated patients who died within day-28., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Godement, Zhu, Cerf, Vieillard-Baron, Maillon, Zuber, Bardet and Geri.)

Objectives: Severe forms of coronavirus disease 2019 (COVID-19) are characterized by an excessive production of inflammatory cytokines. Activated monocytes secrete high levels of cytokines. Human monocytes are divided into three major populations: conventional (CD14 pos CD16 neg ), non-classical (CD14 dim CD16 pos ), and intermediate (CD14 pos CD16 pos ) monocytes. The aim of this study was to analyze whether the distribution of conventional (CD16 neg ) and CD16 pos monocytes is different in patients with COVID-19 and whether the variations could be predictive of the outcome of the disease., Methods: We performed a prospective study on 390 consecutive patients referred to the Emergency Unit, with a proven diagnosis of SARS-CoV 2 infection by RT-PCR. Using the CytoDiff™ reagent, an automated routine leukocyte differential, we quantified CD16 neg and CD16 pos monocytes., Results: In the entire population, median CD16 neg and CD16 pos monocyte levels (0.398 and 0.054×10 9 /L, respectively) were in the normal range [(0.3-0.7×10 9 /L) and (0.015-0.065×10 9 /L), respectively], but the 35 patients in the intensive care unit (ICU) had a significantly (p<0.001) lower CD16 pos monocyte count (0.018 × 10 9 /L) in comparison to the 70 patients who were discharged (0.064 × 10 9 /L) or were hospitalized in conventional units (0.058 × 10 9 /L). By ROC curve analysis, the ratio [absolute neutrophil count/CD16 pos monocyte count] was highly discriminant to identify patients requiring ICU hospitalization: with a cut-off 193.1, the sensitivity and the specificity were 74.3 and 81.8%, respectively (area under the curve=0.817)., Conclusions: Quantification of CD16 pos monocytes and the ratio [absolute neutrophil count/CD16 pos monocyte count] could constitute a marker of the severity of disease in COVID-19 patients., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: To compare intraoperative patterns among patients based on their primary pulmonary disease (cystic fibrosis [CF], chronic obstructive pulmonary disease [COPD]/emphysema [CE], and pulmonary fibrosis [PF]) during double- lung transplantation. The following 3 major outcomes were reported: blood transfusion, extracorporeal membrane oxygenation (ECMO) management, and the possibility of immediate extubation at the end of surgery., Design: Retrospective analysis of a prospectively maintained database, including donor and recipient characteristics and intraoperative variables., Setting: Foch Hospital, Suresnes, France (academic center performing 60-80 lung transplantations per year)., Participants: Patients who underwent double- lung transplantation from 2012-2019. Patients with retransplantation, multiorgan transplantation, or surgery performed with cardiopulmonary bypass were excluded., Interventions: None., Measurements and Main Results: Two hundred forty-six patients had CF, 117 had CE, and 66 had PF. No patient had primary pulmonary arterial hypertension. Blood transfusion was higher in the CF group than in the other 2 groups (red blood cells [p < 0.001], fresh frozen plasma [p = 0.004]). The CF and CE groups were characterized by a lower intraoperative requirement of ECMO (p = 0.002), and the PF group more frequently required postoperative ECMO (p < 0.001). CF and CE patients were more frequently extubated in the operating room than were PF patients (37.4%, 50.4%, and 13.6%, respectively; p < 0.001)., Conclusions: Intraoperative outcomes differed depending on the initial pathology. Such differences should be taken into account in specific clinical studies and in intraoperative management protocols., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: High levels of serum interleukin-6 (IL-6) correlate with disease severity in COVID-19. We hypothesized that tocilizumab (a recombinant humanized anti-IL-6 receptor) could improve outcomes in selected patients with severe worsening COVID-19 pneumonia and high inflammatory parameters., Methods: The TOCICOVID study included a prospective cohort of patients aged 16-80 years with severe (requiring > 6 L/min of oxygen therapy to obtain Sp02 > 94%) rapidly deteriorating (increase by ≥ 3 L/min of oxygen flow within the previous 12 h) COVID-19 pneumonia with ≥ 5 days of symptoms and C-reactive protein levels > 40 mg/L. They entered a compassionate use program of treatment with intravenous tocilizumab (8 mg/kg with a maximum of 800 mg per infusion; and if needed a second infusion 24 to 72 h later). A control group was retrospectively selected with the same inclusion criteria. Outcomes were assessed at D28 using inverse probability of treatment weighted (IPTW) methodology., Results: Among the 96 patients included (81% male, mean (SD) age: 60 (12.5) years), underlying conditions, baseline disease severity, and concomitant medications were broadly similar between the tocilizumab (n = 49) and the control (n = 47) groups. In the IPTW analysis, treatment with tocilizumab was associated with a reduced need for overall ventilatory support (49 vs. 89%, wHR: 0.39 [0.25-0.56]; p < 0.001). Albeit lacking statistical significance, there was a substantial trend towards a reduction of mechanical ventilation (31% vs. 45%; wHR: 0.58 [0.36-0.94]; p = 0.026). However, tocilizumab did not improve overall survival (wHR = 0.68 [0.31-1.748], p = 0.338). Among the 85 (89%) patients still alive at D28, patients treated with tocilizumab had a higher rate of oxygen withdrawal (82% vs. 73.5%, wHR = 1.66 [1.17-2.37], p = 0.005), with a shorter delay before being weaned of oxygen therapy (mean 11 vs. 16 days; p < 0.001). At D28, the rate of patients discharged from hospital was higher in the tocilizumab group (70% vs. 40%, wHR = 1.82 [1.22-2.75]; p = 0.003). The levels of CRP and fibrinogen post therapy (p < 0.001 for both variables) were significantly lower in the tocilizumab group (interaction test, mixed model). Rates of neutropenia (35% vs. 0%; p < 0.001) were higher in the tocilizumab group, yet rates of infections (22% vs. 38%, p = 0.089) including ventilator-acquired pneumonia (8% vs. 26%, p = 0.022) were higher in the control group., Conclusion: These data could be helpful for the design of future trials aiming to counter COVID-19-induced inflammation, especially before patients require admission to the intensive care unit.

In the hospital department dedicated to COVID-19-patient, infection prevention and control measures were upgraded. Therefore, the cross-transmission of other micro-organisms was thought unlikely to occur. However, we report an outbreak of NDM-5-producing Escherichia. coli in a 12-beds ICU dedicated to COVID-19 patients. This outbreak involved 6 patients of which 5 were asymptomatic carriers and 1 was infected. Several findings might have contributed to cross-transmission including the multiple-bedroom configuration of the department, uncomplete compliance for standard and contact precautions, overwork due to the burden of the disease, lack of training of staff for the care of ICU-patients, and misuse of gloves. Furthermore, as infection prevention and control measures were thought to be applied, contact patients were not screened for eXDR carriage. Applying rigorously standard and contact precautions and performing screening in contact patients when indicated must be the rules in COVID-19 wards., (Copyright © 2020 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Poisoning is one of the leading causes of admission to the emergency department and intensive care unit. A large number of epidemiological changes have occurred over the last years such as the exponential growth of new synthetic psychoactive substances. Major progress has also been made in analytical screening and assays, enabling the clinicians to rapidly obtain a definite diagnosis., Methods: A committee composed of 30 experts from five scientific societies, the Société de Réanimation de Langue Française (SRLF), the Société Française de Médecine d'Urgence (SFMU), the Société de Toxicologie Clinique (STC), the Société Française de Toxicologie Analytique (SFTA) and the Groupe Francophone de Réanimation et d'Urgences Pédiatriques (GFRUP) evaluated eight fields: (1) severity assessment and initial triage; (2) diagnostic approach and role of toxicological analyses; (3) supportive care; (4) decontamination; (5) elimination enhancement; (6) place of antidotes; (7) specificities related to recreational drug poisoning; and (8) characteristics of cardiotoxicant poisoning. Population, Intervention, Comparison, and Outcome (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Analysis of the literature and formulation of recommendations were then conducted according to the GRADE ® methodology., Results: The SRLF-SFMU guideline panel provided 41 statements concerning the management of pharmaceutical and recreational drug poisoning. Ethanol and chemical poisoning were excluded from the scope of these recommendations. After two rounds of discussion and various amendments, a strong consensus was reached for all recommendations. Six of these recommendations had a high level of evidence (GRADE 1±) and six had a low level of evidence (GRADE 2±). Twenty-nine recommendations were in the form of expert opinion recommendations due to the low evidences in the literature., Conclusions: The experts reached a substantial consensus for several strong recommendations for optimal management of pharmaceutical and recreational drug poisoning, mainly regarding the conditions and effectiveness of naloxone and N-acetylcystein as antidotes to treat opioid and acetaminophen poisoning, respectively.

Background: Extracorporeal membrane oxygenation (ECMO) is commonly used during double-lung transplantation. ECMO can be planned or unplanned, and used only during the procedure or extended postoperatively (intraoperative or extended). Our practice is to limit its use and duration as much as possible. We conducted this retrospective single-center study to assess prognoses of patients undergoing unplanned-intraoperative ECMO., Methods: From among 436 patients who underwent double-lung transplantation from 2012 to 2018, we excluded those who underwent bridge-to-transplantation, multiorgan transplantation, repeated transplantation during the study period, and cardiopulmonary bypass. Unplanned-intraoperative ECMO group was compared with no-ECMO and planned-intraoperative ECMO groups., Results: In our sample, 209 patients did not require ECMO, 77 underwent unplanned-intraoperative ECMO, and 14 underwent planned-intraoperative ECMO. One-year and 3-year survival were lower in unplanned-intraoperative ECMO group than in the no-ECMO group (P = .043 and P = .032, respectively). The only independent protective factor related to 1-year mortality was history of cystic fibrosis (P = .013). Lung allocation score (P = .001), grade 3 pulmonary graft dysfunction at end-surgery status (P = .014), and estimated intraoperative blood loss (P = .031) were risk factors., Conclusions: Patients who underwent unplanned-intraoperative ECMO showed poorer prognoses than patients who did not require ECMO. This finding may be explained by differences in initial condition severity, by long-term consequences of the intraoperative complications leading to ECMO pump implantation, or by flaws in our weaning protocol., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: We evaluated the prognostic role of the arterial oxygen partial pressure/fractional inspired oxygen ratio (PaO 2 /FiO 2 ratio) measured at the end of double-lung transplantation (DLT)., Methods: This was a monocentric cohort study of all consecutive DLT patients between January 1, 2012, and January 1, 2016, except patients with preoperative extracorporeal membrane oxygenation (ECMO), intraoperative cardiopulmonary bypass, postoperative ECMO, large patent foramen ovale, redo transplantation during the study period, and multiorgan transplantation., Results: A total of 164 patients were included in the study; 45 had a PaO 2 /FiO 2 ratio <200, 39 a ratio in the range 200-300, and 80 a ratio >300. The risk of being in the lower ratio group is positively related to body mass index, preoperative pulmonary hypertension, and fibrosis. It is negatively related to emergency surgery, age, and intraoperative institution of ECMO. There was a trend for more grade 3 pulmonary graft dysfunction at day 3 in the worst PaO 2 /FiO 2 ratio group. Mortality at 1000 days was similar for all patients and even after exclusion of patients who had required intraoperative ECMO., Conclusion: PaO 2 /FiO 2 ratio measured at the end of DLT does not forecast 1000-day mortality., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Inhaled nitric oxide (iNO) is usually used during lung transplantation despite controversial postoperative benefits. Our group chose to administer iNO systematically during the procedure and stop at the end of surgery. This study aims to describe the features of patients who cannot be weaned from iNO, the reasons for this and its impact on postoperative outcomes. This is a monocentric cohort study comprised all consecutive patients who underwent double-lung transplantation (DLT) between 1 January 2012 and 1 January 2016. The impact of iNO dependency on postoperative outcomes was estimated using a boosted inverse probability of treatment weighting estimator. A total of 9.8% of the 173 patients included in the study could not be weaned from iNO at end-surgery stage. Body mass index (OR = 2.03, 95% CI = 1.14-3.29, P = 0.02) and intraoperative extracorporeal membrane oxygenation (OR = 1.80, 95% CI = 1.02-2.72, P = 0.04) were risk factors for iNO dependency In the weighted population, iNO dependency was associated with an increased prevalence of grade 3 primary graft dysfunction (adjusted RR = 4.20, 95% CI = 1.75-10.09, P < 0.001) and decreased postoperative survival during the first 1500 days of follow-up (adjusted HR = 5.0, 95% CI = 1.86-13.48, P < 0.001). Inhaled nitric oxide dependency is an early marker of a poor prognosis following DLT., (© 2018 Steunstichting ESOT.)

Lung transplantation is deemed to be the only effective therapy that improves survival for patients with end stage lung disease. The aim of our study was to examine the progress achieved over the last two decades and to demonstrate the effectiveness and safety of this treatment., Methods: A retrospective analysis of a cohort of 600 consecutive lung transplant patients treated at the hospital Foch (Suresnes, France) between 1988 and 2014. They were split into three groups of 200 patients each: 1988-2004, 2004-2011, 2011-2014., Results: Time and mortality on waiting list, perioperative mortality, the incidence of acute rejection in the first year and chronic lung allograft dysfunction (CLAD) at 5 years posttransplantation, have all decreased. Global survival at 1 and 5 years for the 600 patients increased from 78% and 57% to 86% and 75% respectively for the 200 last patients. Patients with cystic fibrosis have a better 5 year survival than those with emphysema or pulmonary fibrosis (68% vs. 54 % for emphysema and 37% for fibrosis). For the last 200 patients, 5 year survival is 81% for CF patients, 78 % for emphysema and 47% for fibrosis. Emergency transplantation had a 60% 5 years survival. Proliferative complications, arterial hypertension and renal function impairment are being monitored long term., Conclusion: The twenty-five years experience shows a consistent improvement in the results of lung transplantation which is now accepted as the only effective curative treatment for end stage lung disease., (Copyright © 2018 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: Single transpulmonary thermodilution (SD) with extravascular lung water index (EVLWI) could become a new tool to better assess lung graft edema during ex-vivo lung perfusion (EVLP). In this study we compare EVLWI with conventional methods to better select lungs during EVLP and to predict post-transplant primary graft dysfunction (PGD)., Methods: We measured EVLWI, arterial oxygen/fraction of inspired oxygen (P/F) ratio, and static lung compliance (SLC) during EVLP in an observational study. At the end of EVLP, grafts were accepted or rejected according to a standardized protocol blinded to EVLWI results. We compared the respective ability of EVLWI, P/F, and SLC to predict PGD. Mann-Whitney U-test, Fisher's exact test, and receiver-operating characteristic (ROC) curve data were used for analysis. p < 0.05 was considered statistically significant., Results: Thirty-five lungs were evaluated by SD during EVLP. Three lungs were rejected for pulmonary edema. Thirty-two patients were transplanted, 8 patients developed Grade 2 or 3 PGD, and 24 patients developed Grade 0 or 1 PGD. In contrast to P/F ratio, SLC, and pulmonary artery pressure, EVLWI differed between these 2 populations (p < 0.001). The area under the ROC for EVLWI assessing Grade 2 or 3 PGD at the end of EVLP was 0.93. Donor lungs with EVLWI >7.5 ml/kg were more likely associated with a higher incidence of Grade 2 or 3 PGD at Day 3., Conclusions: Increased EVLWI during EVLP was associated with PGD in recipients., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: 22q11.2 deletion syndrome, also known as velo-cardio-facial syndrome (VCFS) is a genetic disorder caused by a microdeletion on chromosome 22q11.2 and characterized by marked impairment in visual attention and executive function. The present study examined if this cognitive deficit extends to prospective memory (the type of memory involved in remembering to perform actions in the future)., Method: 20 participants with 22q11.2DS aged between 6 and 14 were included in the study as well as 22 typically developing individuals (TDC) aged 6-12. To measure prospective memory, participants were asked to play a driving game (the Dresden Cruiser). This time-based prospective memory task required children to remember to refuel their car when the fuel level was low by pressing a refuel button while driving., Results and Discussion: Participants with 22q11.2DS remembered less often to refuel the car. Furthermore, participants with 22q11.2DS checked the fuel gage significantly less often than the controls., Conclusions: Participants with 22q11.2DS therefore demonstrate difficulties completing a time-based prospective memory task. This can be explained by a generally less frequent time checking behavior in comparison to TDC.