Publications by authors named "Nicolas de Prost"

138 Publications

Energetic dysfunction in sepsis: a narrative review.

Ann Intensive Care 2021 Jul 3;11(1):104. Epub 2021 Jul 3.

Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Ulm, Germany.

Background: Growing evidence associates organ dysfunction(s) with impaired metabolism in sepsis. Recent research has increased our understanding of the role of substrate utilization and mitochondrial dysfunction in the pathophysiology of sepsis-related organ dysfunction. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions.

Main Text: Sepsis is characterized by systemic and organ-specific changes in metabolism. Alterations of oxygen consumption, increased levels of circulating substrates, impaired glucose and lipid oxidation, and mitochondrial dysfunction are all associated with organ dysfunction and poor outcomes in both animal models and patients. The pathophysiological relevance of bioenergetics and metabolism in the specific examples of sepsis-related immunodeficiency, cerebral dysfunction, cardiomyopathy, acute kidney injury and diaphragmatic failure is also described.

Conclusions: Recent understandings in substrate utilization and mitochondrial dysfunction may pave the way for new diagnostic and therapeutic approaches. These findings could help physicians to identify distinct subgroups of sepsis and to develop personalized treatment strategies. Implications for their use as bioenergetic targets to identify metabolism- and mitochondria-targeted treatments need to be evaluated in future studies.
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http://dx.doi.org/10.1186/s13613-021-00893-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254847PMC
July 2021

Long-term quality of life in necrotizing soft-tissue infection survivors: a monocentric prospective cohort study.

Ann Intensive Care 2021 Jul 2;11(1):102. Epub 2021 Jul 2.

Service de Médecine Intensive Réanimation, Hôpitaux Universitaires Henri Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Créteil, France.

Background: Compared to other life-threatening infection survivors, long-term health-related quality of life (QOL) of patients surviving necrotizing soft-tissue infections (NSTI) and its determinants are little known. In this monocentric prospective cohort including NSTI survivors admitted between 2014 and 2017, QOL was assessed during a phone interview using the 36-Item Short-Form Health Survey (SF-36), the Hospital Anxiety and Depression (HAD), the activity of daily living (ADL), instrumental ADL (IADL) scales and the Impact of Event Scale-Revised (IES-R). The primary outcome measure was the SF-36 physical component summary (PCS). NSTI patients were compared according to intensive care unit (ICU) admission status. ICU survivors were matched on SAPS II with non-NSTI related septic shock survivors.

Results: Forty-nine NSTI survivors were phone-interviewed and included in the study. Median PCS was decreased compared to the reference population [- 0.97 (- 2.27; - 0.08) SD]. Previous cardiac disease was the only variable associated with PCS alteration [multivariate regression coefficient: - 8.86 (- 17.64; - 0.07), p  =  0.048]. Of NSTI survivors, 15.2% had a HAD-D score  ≥  5 and 61.2% an IES-R score  ≥  33. ICU admission was not associated with lower PCS [35.21 (25.49-46.54) versus (vs) 41.82 (24.12-51.01), p  =  0.516], but with higher IES-R score [14 (7.5-34) vs 7 (3-18), p  =  0.035] and a higher proportion of HAD-D score  ≥  5 (28.6 vs 4.0%, p  =  0.036). Compared to non-NSTI septic shock-matched controls, NSTI patients had similar PCS [33.81 (24.58; - 44.39) vs 44.87 (26.71; - 56.01), p  =  0.706] but higher HAD-D [3.5 (1-7) vs 3 (1.5-6), p  =  0.048] and IES-R scores [18 (8-35) vs 8 (3-19), p  =  0.049].

Conclusions: Long-term QOL in NSTI survivors is severely impaired, similarly to that of non-NSTI septic shock patients for physical compartments, but with more frequent depressive and/or post-traumatic stress disorders. Only ICU admission and previous cardiac disease were predictive of QOL impairment.
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http://dx.doi.org/10.1186/s13613-021-00891-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253876PMC
July 2021

Cutaneous and systemic hyperinflammation drives maculopapular drug exanthema in severely ill COVID-19 patients.

Allergy 2021 Jun 22. Epub 2021 Jun 22.

Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.

Background: Coronavirus disease-2019 (COVID-19) has been associated with cutaneous findings, some being the result of drug hypersensitivity reactions such as maculopapular drug rashes (MDR). The aim of this study was to investigate whether COVID-19 may impact the development of the MDR.

Methods: Blood and skin samples from COVID-19 patients (based on a positive nasopharyngeal PCR) suffering from MDR (COVID-MDR), healthy controls, non-COVID-19-related patients with drug rash with eosinophilia and systemic symptoms (DRESS), and MDR were analyzed. We utilized imaging mass cytometry (IMC) to characterize the cellular infiltrate in skin biopsies. Furthermore, RNA sequencing transcriptome of skin biopsy samples and high-throughput multiplexed proteomic profiling of serum were performed.

Results: IMC revealed by clustering analyses a more prominent, phenotypically shifted cytotoxic CD8 T cell population and highly activated monocyte/macrophage (Mo/Mac) clusters in COVID-MDR. The RNA sequencing transcriptome demonstrated a more robust cytotoxic response in COVID-MDR skin. However, severe acute respiratory syndrome coronavirus 2 was not detected in skin biopsies at the time point of MDR diagnosis. Serum proteomic profiling of COVID-MDR patients revealed upregulation of various inflammatory mediators (IL-4, IL-5, IL-6, TNF, and IFN-γ), eosinophil and Mo/Mac -attracting chemokines (MCP-2, MCP-3, MCP-4 and CCL11). Proteomics analyses demonstrated a massive systemic cytokine storm in COVID-MDR compared with the relatively milder cytokine storm observed in DRESS, while MDR did not exhibit such features.

Conclusion: A systemic cytokine storm may promote activation of Mo/Mac and cytotoxic CD8 T cells in severe COVID-19 patients, which in turn may impact the development of MDR.
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http://dx.doi.org/10.1111/all.14983DOI Listing
June 2021

Menstrual toxic shock syndrome: a French nationwide multicenter retrospective study.

Clin Infect Dis 2021 Apr 27. Epub 2021 Apr 27.

Centre National de Référence des Staphylocoques, Institut des Agent infectieux, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France.

Background: Studies describing the clinical features and short-term prognosis of patients admitted to the intensive care unit (ICU) for menstrual toxic shock syndrome (m-TSS) are lacking.

Methods: This was a multicenter retrospective cohort study of patients with a clinical diagnosis of m-TSS admitted between January 1, 2005 and December 31, 2020 in 43 French pediatric (n=7) or adult (n=36) ICUs. The aim of the study was to describe the clinical features and short-term prognosis, as well as assess the 2011 Centers for Disease and Control (CDC) diagnostic criteria, of critically ill patients with m-TSS.

Results: In total, 102 patients with m-TSS (median age: 18 [16-24] years) were admitted to one of the participating ICUs. All blood cultures (n=102) were sterile. Methicillin-sensitive Staphylococcus aureus grew from 92 of 96 vaginal samples. Screening for super-antigenic toxin gene sequences was performed for 76 of the 92 (83%) vaginal samples positive for Staphylococcus aureus and TSST-1 isolated from 66 (87%) strains. At ICU admission, no patient met the 2011 CDC criteria for confirmed m-TSS and only 53 (52%) fulfilled the criteria for probable m-TSS. Eighty-one patients (79%) were treated with anti-toxin antibiotic therapy and eight (8%) received intravenous immunoglobulins. Eighty-six (84%) patients required vasopressors and 21 (21%) tracheal intubation. No patient required limb amputation or died in the ICU.

Conclusions: In this large multicenter series of patients included in ICUs for m-TSS, none died or required limb amputation. The CDC criteria should not be used for the clinical diagnosis of m-TSS at ICU admission.
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http://dx.doi.org/10.1093/cid/ciab378DOI Listing
April 2021

Critical illness-related corticosteroid insufficiency during difficult weaning from mechanical ventilation.

Ann Intensive Care 2021 Apr 26;11(1):65. Epub 2021 Apr 26.

AP-HP, DHU A-TVB, Service de Médecine Intensive Réanimation, Centre Hospitalo-Universitaire Henri Mondor, 51, avenue du Mal de Lattre de Tassigny, 94010, Créteil Cedex, France.

Background: Critical illness-related corticosteroid insufficiency (CIRCI) is common during critical illness and is usually associated with poor outcomes, as prolonged duration of mechanical ventilation (MV) and higher mortality. CIRCI may alter cardiac and vascular functions. Weaning-induced pulmonary oedema (WiPO) is a major mechanism of weaning failure. The aim of this study was to evaluate the role of CIRCI in patients with difficult ventilator weaning and its possible relation with WiPO.

Methods: This is a prospective study conducted in the intensive care of a university hospital in France. Patients under MV for more than 24 h, meeting weaning criteria and having failed the first spontaneous breathing trial (SBT) underwent a corticotropin stimulation test, with assessment of total blood cortisol levels immediately before (T) 0.25 mg iv of tetracosactrin and 30 and 60 min afterward. Δ was defined as the difference between the maximal value after the test and T. CIRCI was defined as T < 10 μg/dL (276 nmol/L) and/or Δ < 9 μg/dL (248 nmol/L) and inadequate adrenal reserve as Δ < 9 μg/dL. Biomarkers (natriuretic peptide and protidemia) sampling and echocardiograms were performed during the second SBT and were used to diagnose WiPO, which was defined according to two definitions (one liberal and one conservative) derived from recent publications on the topic. Successful extubation was defined as patient alive without reintubation 7 days after extubation. A competing risk analysis was used to assess extubation failure and mortality.

Results: Seventy-six consecutive patients (63 ± 14 years; 49 men) with difficult weaning were enrolled. CIRCI and inadequate adrenal reserve occurred in 25 (33%) and 17 (22%) patients, respectively. The probability of successful extubation was significantly decreased in patients with CIRCI or inadequate adrenal reserve, as compared to their counterparts, and this association persisted after adjustment on severity (SOFA score at first SBT). WiPO occurred in 44 (58%) and 8 (11%) patients, according to the liberal and conservative definition, respectively. WiPO was not associated with CIRCI nor with inadequate adrenal reserve.

Conclusion: CIRCI was common during difficult weaning and was associated with its prolongation. We did not find a significant association between CIRCI and WiPO.
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http://dx.doi.org/10.1186/s13613-021-00852-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072727PMC
April 2021

Vascular access for renal replacement therapy among 459 critically ill patients: a pragmatic analysis of the randomized AKIKI trial.

Ann Intensive Care 2021 Apr 8;11(1):56. Epub 2021 Apr 8.

French National Institute of Health and Medical Research (INSERM), UMR_S1155, Remodeling and Repair of Renal Tissue, Hôpital Tenon, Sorbonne Université, 75020, Paris, France.

Background: Vascular access for renal replacement therapy (RRT) is routine question in the intensive care unit. Randomized trials comparing jugular and femoral sites have shown similar rate of nosocomial events and catheter dysfunction. However, recent prospective observational data on RRT catheters use are scarce. We aimed to assess the site of RRT catheter, the reasons for catheter replacement, and the complications according to site in a large population of critically ill patients with acute kidney injury.

Patients And Methods: We performed an ancillary study of the AKIKI study, a pragmatic randomized controlled trial, in which patients with severe acute kidney injury (KDIGO 3 classification) with invasive mechanical ventilation, catecholamine infusion or both were randomly assigned to either an early or a delayed RRT initiation strategy. The present study involved all patients who underwent at least one RRT session. Number of RRT catheters, insertion sites, factors potentially associated with the choice of insertion site, duration of catheter use, reason for catheter replacement, and complications were prospectively collected.

Results: Among the 619 patients included in AKIKI, 462 received RRT and 459 were finally included, with 598 RRT catheters. Femoral site was chosen preferentially (n = 319, 53%), followed by jugular (n = 256, 43%) and subclavian (n = 23, 4%). In multivariate analysis, continuous RRT modality was significantly associated with femoral site (OR = 2.33 (95% CI (1.34-4.07), p = 0.003) and higher weight with jugular site [88.9 vs 83.2 kg, OR = 0.99 (95% CI 0.98-1.00), p = 0.03]. Investigator site was also significantly associated with the choice of insertion site (p = 0.03). Cumulative incidence of catheter replacement did not differ between jugular and femoral site [sHR 0.90 (95% CI 0.64-1.25), p = 0.67]. Catheter dysfunction was the main reason for replacement (n = 47), followed by suspected infection (n = 29) which was actually seldom proven (n = 4). No mechanical complication (pneumothorax or hemothorax) occurred.

Conclusion: Femoral site was preferentially used in this prospective study of RRT catheters in 31 French intensive care units. The choice of insertion site depended on investigating center habits, weight, RRT modality. A high incidence of catheter infection suspicion led to undue replacement.
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http://dx.doi.org/10.1186/s13613-021-00843-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032839PMC
April 2021

Comparison of two delayed strategies for renal replacement therapy initiation for severe acute kidney injury (AKIKI 2): a multicentre, open-label, randomised, controlled trial.

Lancet 2021 04;397(10281):1293-1300

Réanimation médicale, CHRU de Lille, Hôpital Roger Salengro, Lille, France.

Background: Delaying renal replacement therapy (RRT) for some time in critically ill patients with severe acute kidney injury and no severe complication is safe and allows optimisation of the use of medical devices. Major uncertainty remains concerning the duration for which RRT can be postponed without risk. Our aim was to test the hypothesis that a more-delayed initiation strategy would result in more RRT-free days, compared with a delayed strategy.

Methods: This was an unmasked, multicentre, prospective, open-label, randomised, controlled trial done in 39 intensive care units in France. We monitored critically ill patients with severe acute kidney injury (defined as Kidney Disease: Improving Global Outcomes stage 3) until they had oliguria for more than 72 h or a blood urea nitrogen concentration higher than 112 mg/dL. Patients were then randomly assigned (1:1) to either a strategy (delayed strategy) in which RRT was started just after randomisation or to a more-delayed strategy. With the more-delayed strategy, RRT initiation was postponed until mandatory indication (noticeable hyperkalaemia or metabolic acidosis or pulmonary oedema) or until blood urea nitrogen concentration reached 140 mg/dL. The primary outcome was the number of days alive and free of RRT between randomisation and day 28 and was done in the intention-to-treat population. The study is registered with ClinicalTrial.gov, NCT03396757 and is completed.

Findings: Between May 7, 2018, and Oct 11, 2019, of 5336 patients assessed, 278 patients underwent randomisation; 137 were assigned to the delayed strategy and 141 to the more-delayed strategy. The number of complications potentially related to acute kidney injury or to RRT were similar between groups. The median number of RRT-free days was 12 days (IQR 0-25) in the delayed strategy and 10 days (IQR 0-24) in the more-delayed strategy (p=0·93). In a multivariable analysis, the hazard ratio for death at 60 days was 1·65 (95% CI 1·09-2·50, p=0·018) with the more-delayed versus the delayed strategy. The number of complications potentially related to acute kidney injury or renal replacement therapy did not differ between groups.

Interpretation: In severe acute kidney injury patients with oliguria for more than 72 h or blood urea nitrogen concentration higher than 112 mg/dL and no severe complication that would mandate immediate RRT, longer postponing of RRT initiation did not confer additional benefit and was associated with potential harm.

Funding: Programme Hospitalier de Recherche Clinique.
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http://dx.doi.org/10.1016/S0140-6736(21)00350-0DOI Listing
April 2021

Viral genomic, metagenomic and human transcriptomic characterization and prediction of the clinical forms of COVID-19.

PLoS Pathog 2021 03 29;17(3):e1009416. Epub 2021 Mar 29.

Department of Microbiology, Hôpitaux Universitaires Henri Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Créteil, France.

COVID-19 is characterized by respiratory symptoms of various severities, ranging from mild upper respiratory signs to acute respiratory failure/acute respiratory distress syndrome associated with a high mortality rate. However, the pathophysiology of the disease is largely unknown. Shotgun metagenomics from nasopharyngeal swabs were used to characterize the genomic, metagenomic and transcriptomic features of patients from the first pandemic wave with various forms of COVID-19, including outpatients, patients hospitalized not requiring intensive care, and patients in the intensive care unit, to identify viral and/or host factors associated with the most severe forms of the disease. Neither the genetic characteristics of SARS-CoV-2, nor the detection of bacteria, viruses, fungi or parasites were associated with the severity of pulmonary disease. Severe pneumonia was associated with overexpression of cytokine transcripts activating the CXCR2 pathway, whereas patients with benign disease presented with a T helper "Th1-Th17" profile. The latter profile was associated with female gender and a lower mortality rate. Our findings indicate that the most severe cases of COVID-19 are characterized by the presence of overactive immune cells resulting in neutrophil pulmonary infiltration which, in turn, could enhance the inflammatory response and prolong tissue damage. These findings make CXCR2 antagonists, in particular IL-8 antagonists, promising candidates for the treatment of patients with severe COVID-19.
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http://dx.doi.org/10.1371/journal.ppat.1009416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032121PMC
March 2021

Continuous positive airway pressure for respiratory support during COVID-19 pandemic: a frugal approach from bench to bedside.

Ann Intensive Care 2021 Mar 2;11(1):38. Epub 2021 Mar 2.

Assistance Publique-Hôpitaux de Paris, CHU Henri Mondor-Albert Chenevier, Service de Médecine Intensive Réanimation, 51, Avenue du Maréchal de Lattre de Tassigny, 94010, Créteil Cedex, France.

Background: We describe a frugal approach (focusing on needs, performance, and costs) to manage a massive influx of COVID-19 patients with acute hypoxemic respiratory failure (AHRF) using the Boussignac valve protected by a filter ("Filter Frugal CPAP", FF-CPAP) in and out the ICU.

Methods: (1) A bench study measured the impact of two filters with different mechanical properties on CPAP performances, and pressures were also measured in patients. (2) Non-ICU healthcare staff working in COVID-19 intermediate care units were trained with a video tutorial posted on a massive open online course. (3) A clinical study assessed the feasibility and safety of using FF-CPAP to maintain oxygenation and manage patients out of the ICU during a massive outbreak.

Results: Bench assessments showed that adding a filter did not affect the effective pressure delivered to the patient. The resistive load induced by the filter variably increased the simulated patient's work of breathing (6-34%) needed to sustain the tidal volume, depending on the filter's resistance, respiratory mechanics and basal inspiratory effort. In patients, FF-CPAP achieved pressures similar to those obtained on the bench. The massive training tool provided precious information on the use of Boussignac FF-CPAP on COVID-19 patients. Then 85 COVID-19 patients with ICU admission criteria over a 1-month period were studied upon FF-CPAP initiation for AHRF. FF-CPAP significantly decreased respiratory rate and increased SpO. Thirty-six (43%) patients presented with respiratory indications for intubation prior to FF-CPAP initiation, and 13 (36%) of them improved without intubation. Overall, 31 patients (36%) improved with FF-CPAP alone and 17 patients (20%) did not require ICU admission. Patients with a respiratory rate > 32 breaths/min upon FF-CPAP initiation had a higher cumulative probability of intubation (p < 0.001 by log-rank test).

Conclusion: Adding a filter to the Boussignac valve does not affect the delivered pressure but may variably increase the resistive load depending on the filter used. Clinical assessment suggests that FF-CPAP is a frugal solution to provide a ventilatory support and improve oxygenation to numerous patients suffering from AHRF in the context of a massive outbreak.
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http://dx.doi.org/10.1186/s13613-021-00828-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924341PMC
March 2021

Plasma Exchange to Rescue Patients with Autoantibodies Against Type I Interferons and Life-Threatening COVID-19 Pneumonia.

J Clin Immunol 2021 04 22;41(3):536-544. Epub 2021 Feb 22.

Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Médecine Intensive Réanimation, AP-HP and INSERM UMRS_1166-iCAN, Institute of Cardiometabolism and Nutrition, Paris, France.

Purpose: To report four cases of life-threatening COVID-19 pneumonia in patients with high blood concentrations of neutralizing autoantibodies against type I interferons (IFNs), who were treated with plasma exchange (PE) as a rescue therapy.

Methods: Prospective case series, which included patients, diagnosed with RT-PCR-confirmed SARS-CoV-2 infection and positive autoantibodies against type I IFNs in two French intensive care units (ICUs) between October 8 and November 14, 2020. Six critically ill COVID-19 patients with no anti-IFN antibodies were used as controls. Anti-IFN autoantibodies and IFN concentrations, together with the levels of anti-SARS-CoV-2 antibodies, were measured sequentially in serum. Viral load was determined in the upper and lower respiratory tract. Patients were followed during hospital stay.

Results: Three men and one woman were included. Three of the patients had four PE sessions each, while another had three PE sessions. PE decreased the concentrations of autoantibodies against type I IFN in all four patients, whereas anti-SARS-CoV-2 antibody levels remained stable. Autoantibodies against type I IFN levels were high in tracheal aspirates of one patient and decreased after three PE sessions. By contrast, anti-IFN autoantibodies were not detected in tracheal aspirates from five control patients without detectable anti-IFN autoantibodies in serum. During PE, serum IFN-α levels slightly increased in three out of four patients, and upper respiratory tract viral load decreased in all patients. All patients were alive at day 28 of ICU admission. Two patients eventually died in the ICU, while the two survivors were discharged from the ICU at days 50 and 66.

Conclusions: PE efficiently removes autoantibodies against type I IFNs, including those detected in tracheal aspirates, without affecting anti-SARS-CoV-2 antibody levels, in patients with life-threatening COVID-19 pneumonia. The clinical benefit of PE in patients with autoantibodies against type I IFNs should be tested in a larger study.
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http://dx.doi.org/10.1007/s10875-021-00994-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899072PMC
April 2021

Advanced echocardiographic phenotyping of critically ill patients with coronavirus-19 sepsis: a prospective cohort study.

J Intensive Care 2021 Jan 20;9(1):12. Epub 2021 Jan 20.

AP-HP, Hôpitaux universitaires Henri Mondor, Service de Médecine Intensive Réanimation, 94010, Créteil, France.

Background: Sepsis is characterized by various hemodynamic alterations which could happen concomitantly in the heart, pulmonary and systemic circulations. A comprehensive demonstration of their interactions in the clinical setting of COVID-19 sepsis is lacking. This study aimed at evaluating the feasibility, clinical implications, and physiological coherence of the various indices of hemodynamic function and acute myocardial injury (AMI) in COVID-19 sepsis.

Methods: Hemodynamic and echocardiographic data of septic critically ill COVID-19 patients were prospectively recorded. A dozen hemodynamic indices exploring contractility and loading conditions were assessed. Several cardiac biomarkers were measured, and AMI was considered if serum concentration of high-sensitive troponin T (hs-TNT) was above the 99th percentile, upper reference.

Results: Sixty-seven patients were assessed (55 males), with a median age of 61 [50-70] years. Overall, the feasibility of echocardiographic parameters was very good, ranging from 93 to 100%. Hierarchical clustering method identified four coherent clusters involving cardiac preload, left ventricle (LV) contractility, LV afterload, and right ventricle (RV) function. LV contractility indices were not associated with preload indices, but some of them were positively correlated with RV function parameters and negatively correlated with a single LV afterload parameter. In most cases (n = 36, 54%), echocardiography results prompted therapeutic changes. Mortality was not influenced by the echocardiographic variables in multivariable analysis. Cardiac biomarkers' concentrations were most often increased with high incidence of AMI reaching 72%. hs-TNT was associated with mortality and inversely correlated with most of LV and RV contractility indices.

Conclusions: In this comprehensive hemodynamic evaluation in critically ill COVID-19 septic patients, we identified four homogeneous and coherent clusters with a good feasibility. AMI was common and associated with alteration of LV and RV functions. Echocardiographic assessment had a clinical impact on patient management in most cases.
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http://dx.doi.org/10.1186/s40560-020-00516-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816136PMC
January 2021

Serum cytokines profile of critically ill COVID-19 patients with cardiac dysfunction.

Intensive Care Med Exp 2021 Jan 18;9(1). Epub 2021 Jan 18.

Service de Médecine Intensive Réanimation, AP-HP, CHU Henri Mondor, DHU A-TVB, 51, avenue du Mal de Lattre de Tassigny, 94010, Créteil Cedex, France.

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http://dx.doi.org/10.1186/s40635-021-00368-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812556PMC
January 2021

Alveolar compartmentalization of inflammatory and immune cell biomarkers in pneumonia-related ARDS.

Crit Care 2021 01 9;25(1):23. Epub 2021 Jan 9.

Service de Médecine Intensive Réanimation, Hôpitaux Universitaires Henri Mondor, Assistance Publique-Hôpitaux de Paris, 51, Avenue du Maréchal de Lattre de Tassigny, 94010, Créteil Cedex, France.

Background: Biomarkers of disease severity might help individualizing the management of patients with the acute respiratory distress syndrome (ARDS). Whether the alveolar compartmentalization of biomarkers has a clinical significance in patients with pneumonia-related ARDS is unknown. This study aimed at assessing the interrelation of ARDS/sepsis biomarkers in the alveolar and blood compartments and explored their association with clinical outcomes.

Methods: Immunocompetent patients with pneumonia-related ARDS admitted between 2014 and 2018 were included in a prospective monocentric study. Bronchoalveolar lavage (BAL) fluid and blood samples were obtained within 48 h of admission. Twenty-two biomarkers were quantified in BAL fluid and serum. HLA-DR monocytes and CD8 PD-1 lymphocytes were quantified using flow cytometry. The primary clinical endpoint of the study was hospital mortality. Patients undergoing a bronchoscopy as part of routine care were included as controls.

Results: Seventy ARDS patients were included. Hospital mortality was 21.4%. The BAL fluid-to-serum ratio of IL-8 was 20 times higher in ARDS patients than in controls (p < 0.0001). ARDS patients with shock had lower BAL fluid-to-serum ratio of IL-1Ra (p = 0.026), IL-6 (p = 0.002), IP-10/CXCL10 (p = 0.024) and IL-10 (p = 0.023) than others. The BAL fluid-to-serum ratio of IL-1Ra was more elevated in hospital survivors than decedents (p = 0.006), even after adjusting for SOFA and driving pressure (p = 0.036). There was no significant association between alveolar or alveolar/blood monocytic HLA-DR or CD8 lymphocytes PD-1 expression and hospital mortality.

Conclusions: IL-8 was the most compartmentalized cytokine and lower BAL fluid-to-serum concentration ratios of IL-1Ra were associated with hospital mortality in patients with pneumonia-associated ARDS.
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http://dx.doi.org/10.1186/s13054-020-03427-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794625PMC
January 2021

Risks of ventilator-associated pneumonia and invasive pulmonary aspergillosis in patients with viral acute respiratory distress syndrome related or not to Coronavirus 19 disease.

Crit Care 2020 12 18;24(1):699. Epub 2020 Dec 18.

AP-HP (Assistance Publique-Hôpitaux de Paris), Hôpitaux universitaires Henri Mondor, DMU Médecine, Service de Médecine Intensive Réanimation, 94010, Créteil, France.

Background: Data on incidence of ventilator-associated pneumonia (VAP) and invasive pulmonary aspergillosis in patients with severe SARS-CoV-2 infection are limited.

Methods: We conducted a monocenter retrospective study comparing the incidence of VAP and invasive aspergillosis between patients with COVID-19-related acute respiratory distress syndrome (C-ARDS) and those with non-SARS-CoV-2 viral ARDS (NC-ARDS).

Results: We assessed 90 C-ARDS and 82 NC-ARDS patients, who were mechanically ventilated for more than 48 h. At ICU admission, there were significantly fewer bacterial coinfections documented in C-ARDS than in NC-ARDS: 14 (16%) vs 38 (48%), p < 0.01. Conversely, significantly more patients developed at least one VAP episode in C-ARDS as compared with NC-ARDS: 58 (64%) vs. 36 (44%), p = 0.007. The probability of VAP was significantly higher in C-ARDS after adjusting on death and ventilator weaning [sub-hazard ratio = 1.72 (1.14-2.52), p < 0.01]. The incidence of multi-drug-resistant bacteria (MDR)-related VAP was significantly higher in C-ARDS than in NC-ARDS: 21 (23%) vs. 9 (11%), p = 0.03. Carbapenem was more used in C-ARDS than in NC-ARDS: 48 (53%), vs 21 (26%), p < 0.01. According to AspICU algorithm, there were fewer cases of putative aspergillosis in C-ARDS than in NC-ARDS [2 (2%) vs. 12 (15%), p = 0.003], but there was no difference in Aspergillus colonization.

Conclusions: In our experience, we evidenced a higher incidence of VAP and MDR-VAP in C-ARDS than in NC-ARDS and a lower risk for invasive aspergillosis in the former group.
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http://dx.doi.org/10.1186/s13054-020-03417-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747772PMC
December 2020

Transesophageal echocardiography-associated tracheal microaspiration and ventilator-associated pneumonia in intubated critically ill patients: a multicenter prospective observational study.

Crit Care 2020 12 7;24(1):679. Epub 2020 Dec 7.

DHU A-TVB, Service de Médecine Intensive Réanimation, AP-HP, CHU Henri Mondor, 51, avenue du Mal de Lattre de Tassigny, 94010, Créteil, France.

Background: Microaspiration of gastric and oropharyngeal secretions is the main causative mechanism of ventilator-associated pneumonia (VAP). Transesophageal echocardiography (TEE) is a routine investigation tool in intensive care unit and could enhance microaspiration. This study aimed at evaluating the impact of TEE on microaspiration and VAP in intubated critically ill adult patients.

Methods: It is a four-center prospective observational study. Microaspiration biomarkers (pepsin and salivary amylase) concentrations were quantitatively measured on tracheal aspirates drawn before and after TEE. The primary endpoint was the percentage of patients with TEE-associated microaspiration, defined as: (1) ≥ 50% increase in biomarker concentration between pre-TEE and post-TEE samples, and (2) a significant post-TEE biomarker concentration (> 200 μg/L for pepsin and/or > 1685 IU/L for salivary amylase). Secondary endpoints included the development of VAP within three days after TEE and the evolution of tracheal cuff pressure throughout TEE.

Results: We enrolled 100 patients (35 females), with a median age of 64 (53-72) years. Of the 74 patients analyzed for biomarkers, 17 (23%) got TEE-associated microaspiration. However, overall, pepsin and salivary amylase levels were not significantly different between before and after TEE, with wide interindividual variability. VAP occurred in 19 patients (19%) within 3 days following TEE. VAP patients had a larger tracheal tube size and endured more attempts of TEE probe introduction than their counterparts but showed similar aspiration biomarker concentrations. TEE induced an increase in tracheal cuff pressure, especially during insertion and removal of the probe.

Conclusions: We could not find any association between TEE-associated microaspiration and the development of VAP during the three days following TEE in intubated critically ill patients. However, our study cannot formally rule out a role for TEE because of the high rate of VAP observed after TEE and the limitations of our methods.
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http://dx.doi.org/10.1186/s13054-020-03380-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719845PMC
December 2020

Electrical impedance tomography to titrate positive end-expiratory pressure in COVID-19 acute respiratory distress syndrome.

Crit Care 2020 12 7;24(1):678. Epub 2020 Dec 7.

Assistance Publique - Hôpitaux de Paris, Hôpitaux Universitaires Henri Mondor, Service de Médecine Intensive Réanimation, 51, Avenue du Maréchal de Lattre de Tassigny, 94010, Créteil Cedex, France.

Rationale: Patients with coronavirus disease-19-related acute respiratory distress syndrome (C-ARDS) could have a specific physiological phenotype as compared with those affected by ARDS from other causes (NC-ARDS).

Objectives: To describe the effect of positive end-expiratory pressure (PEEP) on respiratory mechanics in C-ARDS patients in supine and prone position, and as compared to NC-ARDS. The primary endpoint was the best PEEP defined as the smallest sum of hyperdistension and collapse.

Methods: Seventeen patients with moderate-to-severe C-ARDS were monitored by electrical impedance tomography (EIT) and evaluated during PEEP titration in supine (n = 17) and prone (n = 14) position and compared with 13 NC-ARDS patients investigated by EIT in our department before the COVID-19 pandemic.

Results: As compared with NC-ARDS, C-ARDS exhibited a higher median best PEEP (defined using EIT as the smallest sum of hyperdistension and collapse, 12 [9, 12] vs. 9 [6, 9] cmHO, p < 0.01), more collapse at low PEEP, and less hyperdistension at high PEEP. The median value of the best PEEP was similar in C-ARDS in supine and prone position: 12 [9, 12] vs. 12 [10, 15] cmHO, p = 0.59. The response to PEEP was also similar in C-ARDS patients with higher vs. lower respiratory system compliance.

Conclusion: An intermediate PEEP level seems appropriate in half of our C-ARDS patients. There is no solid evidence that compliance at low PEEP could predict the response to PEEP.
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http://dx.doi.org/10.1186/s13054-020-03414-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719729PMC
December 2020

Procalcitonin to Reduce Antibiotic Exposure during Acute Chest Syndrome in Adult Patients with Sickle-Cell Disease.

J Clin Med 2020 Nov 19;9(11). Epub 2020 Nov 19.

DHU A-TVB, Service de Médecine Intensive Réanimation, 51 Avenue du Maréchal de Lattre de Tassigny, AP-HP Hôpitaux Universitaires Henri Mondor, 94010 Créteil, France.

Acute chest syndrome (ACS) is a major complication of sickle-cell disease. Bacterial infection is one cause of ACS, so current guidelines recommend the routine use of antibiotics. We performed a prospective before-after study in medical wards and an intensive-care unit (ICU). During the control phase, clinicians were blinded to procalcitonin concentration results. We built an algorithm using the obtained measurements to hasten antibiotic cessation after three days of treatment if bacterial infection was not documented, and procalcitonin concentrations were all <0.5 μg/L. During the intervention period, the procalcitonin algorithm was suggested to physicians as a guide for antibiotic therapy. The primary endpoint was the number of days alive without antibiotics at Day 21. One-hundred patients were analyzed (103 ACS episodes, 60 in intervention phase). Possible or proven lung infection was diagnosed during 13% of all ACS episodes. The number of days alive without antibiotics at Day 21 was higher during the intervention phase: 15 [14-18] vs. 13 [13,14] days ( = 0.001). More patients had a short (≤3 days) antibiotic course during intervention phase: 31% vs 9% ( = 0.01). There was neither infection relapse nor pulmonary superinfection in the entire cohort. A procalcitonin-guided strategy to prescribe antibiotics in patients with ACS may reduce antibiotic exposure with no apparent adverse outcomes.
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http://dx.doi.org/10.3390/jcm9113718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699579PMC
November 2020

Rescue therapy with inhaled nitric oxide and almitrine in COVID-19 patients with severe acute respiratory distress syndrome.

Ann Intensive Care 2020 Nov 4;10(1):151. Epub 2020 Nov 4.

AP-HP, Hôpitaux Universitaires Henri-Mondor, Service de Médecine Intensive Réanimation, 51, avenue du Maréchal de Lattre de Tassigny, 94010, Créteil, France.

Background: In COVID-19 patients with severe acute respiratory distress syndrome (ARDS), the relatively preserved respiratory system compliance despite severe hypoxemia, with specific pulmonary vascular dysfunction, suggests a possible hemodynamic mechanism for VA/Q mismatch, as hypoxic vasoconstriction alteration. This study aimed to evaluate the capacity of inhaled nitric oxide (iNO)-almitrine combination to restore oxygenation in severe COVID-19 ARDS (C-ARDS) patients.

Methods: We conducted a monocentric preliminary pilot study in intubated patients with severe C-ARDS. Respiratory mechanics was assessed after a prone session. Then, patients received iNO (10 ppm) alone and in association with almitrine (10 μg/kg/min) during 30 min in each step. Echocardiographic and blood gases measurements were performed at baseline, during iNO alone, and iNO-almitrine combination. The primary endpoint was the variation of oxygenation (PaO/FiO ratio).

Results: Ten severe C-ARDS patients were assessed (7 males and 3 females), with a median age of 60 [52-72] years. Combination of iNO and almitrine outperformed iNO alone for oxygenation improvement. The median of PaO/FiO ratio varied from 102 [89-134] mmHg at baseline, to 124 [108-146] mmHg after iNO (p = 0.13) and 180 [132-206] mmHg after iNO and almitrine (p < 0.01). We found no correlation between the increase in oxygenation caused by iNO-almitrine combination and that caused by proning.

Conclusion: In this pilot study of severe C-ARDS patients, iNO-almitrine combination was associated with rapid and significant improvement of oxygenation. These findings highlight the role of pulmonary vascular function in COVID-19 pathophysiology.
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http://dx.doi.org/10.1186/s13613-020-00769-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641257PMC
November 2020

Physiological mechanism and spatial distribution of increased alveolar dead-space in early ARDS: An experimental study.

Acta Anaesthesiol Scand 2021 01 28;65(1):100-108. Epub 2020 Sep 28.

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Background: We aimed to investigate the physiological mechanism and spatial distribution of increased physiological dead-space, an early marker of ARDS mortality, in the initial stages of ARDS. We hypothesized that: increased dead-space results from the spatial redistribution of pulmonary perfusion, not ventilation; such redistribution is not related to thromboembolism (ie, areas with perfusion = 0 and infinite ventilation-perfusion ratio, ), but rather to moderate shifts of perfusion increasing in non-dependent regions.

Methods: Five healthy anesthetized sheep received protective ventilation for 20 hours, while endotoxin was continuously infused. Maps of voxel-level lung ventilation, perfusion, , CO partial pressures, and alveolar dead-space fraction were estimated from positron emission tomography at baseline and 20 hours.

Results: Alveolar dead-space fraction increased during the 20 hours (+0.05, P = .031), mainly in non-dependent regions (+0.03, P = .031). This was mediated by perfusion redistribution away from non-dependent regions (-5.9%, P = .031), while the spatial distribution of ventilation did not change, resulting in increased in non-dependent regions. The increased alveolar dead-space derived mostly from areas with intermediate (0.5≤ ≤10), not areas of nearly "complete" dead-space ( >10).

Conclusions: In this early ARDS model, increases in alveolar dead-space occur within 20 hours due to the regional redistribution of perfusion and not ventilation. This moderate redistribution suggests changes in the interplay between active and passive perfusion redistribution mechanisms (including hypoxic vasoconstriction and gravitational effects), not the appearance of thromboembolism. Hence, the association between mortality and increased dead-space possibly arises from the former, reflecting gas-exchange inefficiency due to perfusion heterogeneity. Such heterogeneity results from the injury and exhaustion of compensatory mechanisms for perfusion redistribution.
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http://dx.doi.org/10.1111/aas.13702DOI Listing
January 2021

Uncontrolled Innate and Impaired Adaptive Immune Responses in Patients with COVID-19 Acute Respiratory Distress Syndrome.

Am J Respir Crit Care Med 2020 12;202(11):1509-1519

Médecine Intensive Réanimation, Hôpitaux Universitaires Henri Mondor.

Uncontrolled inflammatory innate response and impaired adaptive immune response are associated with clinical severity in patients with coronavirus disease (COVID-19). To compare the immunopathology of COVID-19 acute respiratory distress syndrome (ARDS) with that of non-COVID-19 ARDS, and to identify biomarkers associated with mortality in patients with COVID-19 ARDS. Prospective observational monocenter study. Immunocompetent patients diagnosed with RT-PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and ARDS admitted between March 8 and March 30, 2020, were included and compared with patients with non-COVID-19 ARDS. The primary clinical endpoint of the study was mortality at Day 28. Flow cytometry analyses and serum cytokine measurements were performed at Days 1-2 and 4-6 of ICU admission. As compared with patients with non-COVID-19 ARDS ( = 36), those with COVID-19 ( = 38) were not significantly different regarding age, sex, and Sequential Organ Failure Assessment and Simplified Acute Physiology Score II scores but exhibited a higher Day-28 mortality (34% vs. 11%,  = 0.030). Patients with COVID-19 showed profound and sustained T CD4 ( = 0.002), CD8 ( < 0.0001), and B ( < 0.0001) lymphopenia, higher HLA-DR expression on monocytes ( < 0.001) and higher serum concentrations of EGF (epithelial growth factor), GM-CSF, IL-10, CCL2/MCP-1, CCL3/MIP-1a, CXCL10/IP-10, CCL5/RANTES, and CCL20/MIP-3a. After adjusting on age and Sequential Organ Failure Assessment, serum CXCL10/IP-10 ( = 0.047) and GM-CSF ( = 0.050) were higher and nasopharyngeal RT-PCR cycle threshold values lower ( = 0.010) in patients with COVID-19 who were dead at Day 28. Profound global lymphopenia and a "chemokine signature" were observed in COVID-19 ARDS. Increased serum concentrations of CXCL10/IP-10 and GM-CSF, together with higher nasopharyngeal SARS-CoV-2 viral load, were associated with Day-28 mortality.
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http://dx.doi.org/10.1164/rccm.202005-1885OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706149PMC
December 2020

SARS-CoV-2 viral loads and serum IgA/IgG immune responses in critically ill COVID-19 patients.

Intensive Care Med 2020 Sep 22;46(9):1781-1783. Epub 2020 Jun 22.

INSERM U955, Université Paris-Est Créteil Val de Marne (UPEC), Créteil, France.

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http://dx.doi.org/10.1007/s00134-020-06157-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306494PMC
September 2020

Severe diffuse alveolar hemorrhage related to autoimmune disease: a multicenter study.

Crit Care 2020 05 18;24(1):231. Epub 2020 May 18.

Département Hospitalo-Universitaire Inflammation-Immunopathologie-Biotherapie (DHU i2B), UPMC Université Paris 06, UMR 7211, Sorbonne Universités, 75005, Paris, France.

Background: Diffuse alveolar hemorrhage (DAH) occurs during the course of autoimmune disease and may be life threatening. The objective was to assess characteristics and prognosis factors of DAH who required intensive care unit (ICU) admission in patients with autoimmune diseases.

Methods: French multicenter retrospective study including patients presenting DAH related to autoimmune diseases requiring ICU admission from 2000 to 2016.

Results: One hundred four patients (54% of men) with median age of 56 [32-68] years were included with 79 (76%) systemic vasculitis and 25 (24%) connective tissue disorders. All patients received steroids, and 72 (69%), 12 (11.5%), and 57 (55%) patients had cyclophosphamide, rituximab, and plasma exchanges, respectively. During ICU stay, 52 (50%), 36 (35%), and 55 (53%) patients required mechanical ventilation, vasopressor use, and renal replacement therapy, respectively. Factors associated with mechanical ventilation weaning were age (HR [95%CI] 0.97 [0.96-0.99] per 10 years, p < 0.0001), vasculitis-related DAH (0.52 [0.27-0.98], p = 0.04), and time from dyspnea onset to ICU admission (0.99 [0.99-1] per day, p = 0.03). ICU mortality was 15%. Factors associated with alive status at ICU discharge were chronic cardiac failure (HR [95%CI] 0.37 [0.15-0.94], p = 0.04), antiphospholipid syndrome-related DAH (3.17 [1.89-5.32], p < 0.0001), SAPS II (0.98 [0.97-0.99], p = 0.007), and oxygen flow at ICU admission (0.95 [0.91-0.99] per liter/min, p = 0.04).

Conclusion: DAH in autoimmune diseases is a life-threatening complication which requires mechanical ventilation in half of the cases admitted to ICU.
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http://dx.doi.org/10.1186/s13054-020-02936-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236262PMC
May 2020

Understanding necrotizing soft tissue infections in the intensive care unit.

Intensive Care Med 2020 09 11;46(9):1739-1742. Epub 2020 May 11.

Service de Médecine Intensive Réanimation, Hôpitaux Universitaires Henri Mondor, Assistance Publique - Hôpitaux de Paris (AP-HP), Créteil, France.

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http://dx.doi.org/10.1007/s00134-020-06071-wDOI Listing
September 2020

Antiviral treatment strategy should be individualized in critically ill patients with severe influenza.

Intensive Care Med 2020 06 14;46(6):1292-1293. Epub 2020 Apr 14.

Médecine Intensive Réanimation, Hôpitaux Universitaires Henri Mondor - Albert Chenevier, Assistance Publique - Hôpitaux de Paris (AP-HP), Créteil, France.

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http://dx.doi.org/10.1007/s00134-020-06032-3DOI Listing
June 2020

Interstitial Lung Disease-Complicated Anti-MDA5 Antibody in Clinically Amyopathic Dermatomyositis Patients: Report of Two Cases With Distinct Clinical Features.

Front Med (Lausanne) 2020 10;7:77. Epub 2020 Mar 10.

Service d'Immunologie Biologique, Hôpital Européen Georges Pompidou, Paris, France.

Two patients presented simultaneously to our hospital with distinct clinical features associated with the presence of anti-MDA5 antibodies: the first one was admitted for a skin rash resembling to a toxic epidermal necrosis (Lyell syndrome) and the second one presented with pulmonary manifestations attributed to a diffuse fibrosing interstitial pneumonitis on chest CT-scan. In addition to the skin lesions involving 40% of the body surface area, the first patient developed a rapid diffuse interstitial pneumonitis with respiratory distress justifying the initiation of a systemic immunosuppressive treatment. However, she died 3 weeks after her admission from mesenteric thrombosis associated with septic shock. The second patient respiratory condition worsened despite an intensive immunosuppressive treatment with high doses of intravenous methylprednisolone and cyclophosphamide and plasmapheresis, and required lung transplantation. Anti-MDA5 antibody titer declined and disappeared on anti-rejection treatment. These two cases underline the diagnostic conundrum and the therapeutic difficulties in patients with anti-MDA5 antibodies and clinically amyopathic dermatomyositis (CADM) or interstitial lung disease (ILD), who may undergo rapidly-progressive and fatal outcome. Presence of anti-MDA5 antibodies should always be suspected when confronted to CADM patients with cutaneous ulcerations or ILD to allow a rapid and adapted treatment initiation.
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http://dx.doi.org/10.3389/fmed.2020.00077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076087PMC
March 2020

Inflammatory Activity in Atelectatic and Normally Aerated Regions During Early Acute Lung Injury.

Acad Radiol 2020 12 12;27(12):1679-1690. Epub 2020 Mar 12.

Massachusetts General Hospital, Department of Anesthesia, Critical Care and Pain Medicine, 55 Fruit St. Boston, MA.

Rationale And Objectives: Pulmonary atelectasis presumably promotes and facilitates lung injury. However, data are limited on its direct and remote relation to inflammation. We aimed to assess regional 2-deoxy-2-[F]-fluoro-D-glucose (F-FDG) kinetics representative of inflammation in atelectatic and normally aerated regions in models of early lung injury.

Materials And Methods: We studied supine sheep in four groups: Permissive Atelectasis (n = 6)-16 hours protective tidal volume (V) and zero positive end-expiratory pressure; Mild (n = 5) and Moderate Endotoxemia (n = 6)- 20-24 hours protective ventilation and intravenous lipopolysaccharide (Mild = 2.5 and Moderate = 10.0 ng/kg/min), and Surfactant Depletion (n = 6)-saline lung lavage and 4 hours high V. Measurements performed immediately after anesthesia induction served as controls (n = 8). Atelectasis was defined as regions of gas fraction <0.1 in transmission or computed tomography scans. F-FDG kinetics measured with positron emission tomography were analyzed with a three-compartment model.

Results: F-FDG net uptake rate in atelectatic tissue was larger during Moderate Endotoxemia (0.0092 ± 0.0019/min) than controls (0.0051 ± 0.0014/min, p = 0.01). F-FDG phosphorylation rate in atelectatic tissue was larger in both endotoxemia groups (0.0287 ± 0.0075/min) than controls (0.0198 ± 0.0039/min, p = 0.05) while the F-FDG volume of distribution was not significantly different among groups. Additionally, normally aerated regions showed larger F-FDG uptake during Permissive Atelectasis (0.0031 ± 0.0005/min, p < 0.01), Mild (0.0028 ± 0.0006/min, p = 0.04), and Moderate Endotoxemia (0.0039 ± 0.0005/min, p < 0.01) than controls (0.0020 ± 0.0003/min).

Conclusion: Atelectatic regions present increased metabolic activation during moderate endotoxemia mostly due to increased F-FDG phosphorylation, indicative of increased cellular metabolic activation. Increased F-FDG uptake in normally aerated regions during permissive atelectasis suggests an injurious remote effect of atelectasis even with protective tidal volumes.
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http://dx.doi.org/10.1016/j.acra.2019.12.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486228PMC
December 2020