Effect of antifibrotic agents on postoperative complications after lung transplantation for idiopathic pulmonary fibrosis.

BACKGROUND: Antifibrotic agents (AFAs) are now standard-of-care for idiopathic pulmonary fibrosis (IPF). Concerns have arisen about the safety of these drugs in patients undergoing lung transplantation (LTx). METHODS: We performed a multi-centre, nationwide, retrospective, observational study of French IPF patients undergoing LTx between 2011 and 2018 to determine whether maintaining AFAs in the peri-operative period leads to increased bronchial anastomoses issues, delay in skin healing and haemorrhagic complications. We compared the incidence of post-operative complications and the survival of patients according to AFA exposure. RESULTS: Among 205 patients who underwent LTx for IPF during the study period, 58 (28%) had received AFAs within 4 weeks before LTx (AFA group): pirfenidone in 37 (18.0%) and nintedanib in 21 (10.2%). The median duration of AFA treatment before LTx was 13.8 (5.6-24) months. The AFA and control groups did not significantly differ in airway, bleeding or skin healing complications (p = 0.91, p = 0.12 and p = 0.70, respectively). Primary graft dysfunction was less frequent in the AFA than control group (26% vs. 43%, p = 0.02), and the 90-day mortality was lower (7% vs. 18%, p = 0.046). CONCLUSIONS: AFA therapy did not increase airway, bleeding or wound post-operative complications after LTx and could be associated with reduced rates of primary graft dysfunction and 90-day mortality.

Ultrasonography in thoracic and abdominal stab wound injury: results from the FETTHA study.

BACKGROUND: While the role of Extended Focused Assessment with Sonography in Trauma (eFAST) is well defined in the management of severe blunt trauma, its performance in injuries caused by stab wounds has been poorly assessed. METHODS: Prospective single centre study which included all patients with stab wounds to the thorax or abdomen between December 2016 and December 2018. All patients underwent initial investigation with both eFAST and CT scan, except in cases of haemodynamic or respiratory instability, and in cases with a positive diagnosis by eFAST in which case surgery without CT scan was performed. RESULTS: Of the 200 consecutive patients included, 14 unstable patients underwent surgery immediately after eFAST. In these 14 patients, 9 had cardiac tamponade identified by eFAST and all were confirmed by surgery. In the remaining 186 patients, the median time between eFAST and CT scan was 30 min (IQR 20-49 min). Test characteristics (including 95% CI) for eFAST compared with reference standard of CT scan for detecting pneumothorax were as follows: sensitivity 77% (54%-92%), specificity 93% (90%-97%), positive predictive value (PPV) 60% (49%-83%), negative predictive value (NPV) 97% (93%-99%). Test characteristics (including 95% CI) for eFAST compared with CT scan for detecting haemothorax were as follows: sensitivity 97% (74%-99%), specificity 96% (92%-98%), PPV 83% (63%-93%) and NPV 99% (96%-100%). Finally, test characteristics (including 95% CI) for eFAST compared with CT scan for detecting haemoperitoneum were as follows: sensitivity 75% (35%-97%), specificity 97% (93%-99%), PPV 55% (23%-83%) and NPV 99% (96%-99%). CONCLUSIONS: In patients admitted with stab wounds to the torso, eFAST was not sensitive enough to diagnose pneumothorax and haemoperitoneum, but performed better in the detection of cardiac tamponade and haemothorax than the other injuries. More robust multicentre studies are needed to better define the role of eFAST in this specific population.

A 24-Year-Old Woman With Cough, Arthralgia, and Skin Ulcerations.

CASE PRESENTATION: A 24-year-old Senegalese woman without remarkable history except anemia and iron deficiency related to excessive menstrual bleeding and sickle cell trait was admitted to our internal medicine department with 4-month fever, weight loss (-13 kg), dyspnea for limited efforts, intermittent productive cough, and bilateral metacarpophalangeal (MCP) and interphalangeal arthralgia. She was born and lived in France. She traveled previously to Senegal in 2015. She had no history of tobacco, alcohol, or drug use nor proximity with animals. She was taking no medication.

Prolonged mechanical ventilation after lung transplantation: risks factors and consequences on recipient outcome.

Background: Risk factors and the incidence of prolonged mechanical ventilation (PMV) after lung transplantation (LT) have been poorly described. The study assessed predictive factors of PMV after LT. Methods: This observational, retrospective, monocentric study included all patients who received LT in Bichat Claude Bernard Hospital between January 2016 and December 2020. PMV was defined as a duration of MV > 14 days. Independent risk factors for PMV were studied using multivariate analysis. One-year survival depending on PMV was studied using Kaplan Meier and log-rank tests. A p value <0.05 was defined as significant. Results: 224 LT recipients were analysed. 64 (28%) of them received PMV for a median duration of 34 [26-52] days versus 2 [1-3] days without PMV. Independent risk factors for PMV were higher body mass index (BMI) (p = 0.031), diabetes mellitus of the recipient (p = 0.039), ECMO support during surgery (p = 0.029) and intraoperative transfusion >5 red blood cell units (p < 0.001). Increased mortality rates were observed at one-year in recipients who received PMV (44% versus 15%, p < 0.001). Conclusion: PMV was associated with increased morbidity and mortality one-year after LT. Preoperative risk factors (BMI and diabetes mellitus) must be considered when selecting and conditioning the recipients.

Plasma Apolipoprotein Concentrations Are Highly Altered in Severe Intensive Care Unit COVID-19 Patients: Preliminary Results from the LIPICOR Cohort Study.

SARS-CoV-2 infection goes beyond acute pneumonia, as it also impacts lipid metabolism. Decreased HDL-C and LDL-C levels have been reported in patients with COVID-19. The lipid profile is a less robust biochemical marker than apolipoproteins, components of lipoproteins. However, the association of apolipoprotein levels during COVID-19 is not well described and understood. The objective of our study is to measure plasma levels of 14 apolipoproteins in patients with COVID-19 and to evaluate the relationships between apolipoprotein levels, severity factors and patient outcomes. From November to March 2021, 44 patients were recruited on admission to the intensive care unit because of COVID-19. Fourteen apolipoproteins and LCAT were measured by LC-MS/MS in plasma of 44 COVID-19 patients on admission to the ICU and 44 healthy control subjects. Absolute apolipoprotein concentrations were compared between COVID-19 patients and controls. Plasma apolipoproteins (Apo) A (I, II, IV), C(I, II), D, H, J and M and LCAT were lower in COVID-19 patients, whereas Apo E was higher. COVID-19 severity factors such as PaO2/FiO2 ratio, SO-FA score and CRP were correlated with certain apolipoproteins. Lower Apo B100 and LCAT levels were observed in non-survivors of COVID-19 versus survivors. To conclude, in this study, lipid and apolipoprotein profiles are altered in COVID-19 patients. Low Apo B100 and LCAT levels may be predictive of non-survival in COVID-19 patients.

Impact of Culture-Positive Preservation Fluid on Early Morbidity and Mortality After Lung Transplantation.

The prevalence, risk factors and outcomes associated with culture-positive preservation fluid (PF) after lung transplantation (LT) are unknown. From January 2015 to December 2020, the microbiologic analyses of PF used to store the cold ischaemia-placed lung graft(s) of 271 lung transplant patients were retrospectively studied. Culture-positive PF was defined as the growth of any microorganism. Eighty-three (30.6%) patients were transplanted with lung grafts stored in a culture-positive PF. One-third of culture-positive PF were polymicrobial. Staphylococcus aureus and Escherichia coli were the most frequently isolated microorganisms. No risk factors for culture-positive PF based on donor characteristics were identified. Forty (40/83; 48.2%) patients had postoperative pneumonia on Day 0 and 2 (2/83; 2.4%) patients had pleural empyema with at least one identical bacteria isolated in culture-positive PF. The 30-day survival rate was lower for patients with culture-positive PF compared with patients with culture-negative PF (85.5% vs. 94.7%, p = 0.01). Culture-positive PF has a high prevalence and may decrease lung transplant recipient survival. Further studies are required to confirm these results and improve understanding of the pathogenesis of culture-positive PF and their management.

Low HDL-Cholesterol Concentrations in Lung Transplant Candidates are Strongly Associated With One-Year Mortality After Lung Transplantation.

High-density lipoproteins (HDLs), whose main role is the reverse transport of cholesterol, also have pleiotropic anti-inflammatory, antioxidant, anti-apoptotic and anti-infectious properties. During sepsis, HDL cholesterol (HDL-C) concentration is low, HDL particle functionality is altered, and these modifications are correlated with poor outcomes. Based on the protective effects of HDL, we hypothesized that HDL-C levels could be associated with lung transplantation (LT) outcome. We thus looked for an association between basal HDL-C concentration and one-year mortality after LT. In this single-center prospective study including consecutive LTs from 2015 to 2020, 215 patients were included, essentially pulmonary fibrosis (47%) and chronic obstructive pulmonary disease (COPD) (38%) patients. Mortality rate at one-year was 23%. Basal HDL-C concentration stratified nonsurvivors to survivors at one-year (HDL-C = 1.26 [1.12-1.62] mmol/L vs. HDL-C = 1.55 [1.22-1.97] mmol/L, p = 0.006). Multivariate analysis confirmed that HDL-C concentration during the pretransplant assessment period was the only variable inversely associated with mortality. Moreover, mortality at one-year in patients with HDL-C concentrations ≤1.45 mmol/L was significantly higher (log-rank test, p = 0.00085). In conclusion, low basal HDL-C concentrations in candidates for LT are strongly associated with mortality after LT. To better understand this association, further studies in this field are essential and, in particular, a better characterization of HDL particles seems necessary.

Donors brain-dead after successful resuscitation of cardiac arrest: Early outcome and postoperative complications of lung recipients.

BACKGROUND: The outcomes of lung transplantation (LT) recipients who received a graft from a brain-dead donor after successful resuscitation from cardiac arrest (CA donors) have been poorly described. This study compared the one-year survival of LT recipients depending on the CA status of the donor. METHODS: This prospective observational single-centre study analysed all consecutive patients who underwent LT at Bichat Claude Bernard Hospital, Paris, between January 2016 and December 2020. All donors who experienced CA prior to organ donation, regardless of rhythm or duration, were considered CA donors. The postoperative complications and outcomes of LT recipients were analysed. The one-year survival was compared using Kaplan-Meier curves and log-rank tests. Independent risk factors for one-year mortality were assessed using multivariate analysis (p < 0.05 was considered significant). The Paris North Hospitals Institutional Review Board approved the study. RESULTS: A total of 236 LT recipients were analysed and 66 (28%) received a graft from a CA donor. The median durations of no/low flow were 4 [0-10]/20 [15-30] minutes, respectively. Shockable and non-shockable rhythms were observed in 11 (17%) and 47 (72%) of the CA donors, respectively. The characteristics of the grafts and early postoperative complications were not different in the CA and non-CA groups. Receiving a graft from a CA donor was not an independent risk factor for recipient one-year mortality. CONCLUSION: Receiving a graft from a CA donor did not worsen the outcome of LT recipients. Acceptation of these grafts must be systematically considered to increase the pool of available grafts.

ECMO support as a bridge to lung transplantation is an independent risk factor for bronchial anastomotic dehiscence.

BACKGROUND: Airway complications are frequent after lung transplantation (LT), as they affect up to 23% of recipients. The implication of perioperative extracorporeal membrane oxygenation (ECMO) support and haemodynamic instability has never been specifically assessed. The first aim of this study was to explore the impact of perioperative ECMO support on bronchial anastomotic dehiscence (BAD) at Day 90 after LT. METHODS: This prospective observational monocentric study analysed BAD in all consecutive patients who underwent LT in the Bichat Claude Bernard Hospital, Paris, France, between January 2016 and May 2019. BAD visible on bronchial endoscopy and/or tomodensitometry was recorded. A univariate analysis was performed (Fisher's exacts and Mann-Whitney tests), followed by a multivariate analysis to assess independent risk factors for BAD during the first 90 days after LT (p < 0.05 as significant). The Paris North Hospitals Institutional Review Board approved the study. RESULTS: A total of 156 patients were analysed. BAD was observed in the first 90 days in 42 (27%) patients and was the main cause of death in 22 (14%) patients. BAD occurred during the first month after surgery in 34/42 (81%) patients. ECMO support was used as a bridge to LT, during and after surgery in 9 (6%), 117 (75%) and 40 (27%) patients, respectively. On multivariate analysis, ECMO as a bridge to LT (p = 0.04) and septic shock (p = 0.01) were independent risk factors for BAD. CONCLUSION: ECMO as a bridge to LT is an independent risk factor for BAD during the first 90 days after surgery. Close monitoring of bronchial conditions must be performed in these high-risk recipients.

Temporary ICUs during the COVID-19 pandemic first wave: description of the cohort at a French centre.

BACKGROUND: During the COVID-19 first wave in France, the capacity of intensive care unit (ICU) beds almost doubled, mainly because of the opening of temporary ICUs with staff and equipment from anaesthesia. OBJECTIVES: We aim to investigate if the initial management in temporary ICU is associated with a change in ICU mortality and short-term prognosis. DESIGN: Retrospective single-centre cohort study. SETTING: Surgical ICU of the Bichat Claude Bernard University Hospital during the COVID-19 "first wave" (from 18 March to 10 April 2020). PATIENTS: All consecutive patients older than 18 years of age with laboratory-confirmed SARS-CoV-2 infection and/or typical radiological patterns were included during their first stay in the ICU for COVID-19. INTERVENTION: Patients were admitted to a temporary ICU if no room was available in the classical ICU and if they needed invasive mechanical ventilation but no renal replacement therapy or Extracorporeal Membrane Oxygenation (ECMO) in the short term. The temporary ICUs were managed by mixed teams (from the ICU and anaesthesiology departments) following a common protocol and staff meetings. MAIN OUTCOME MEASURE: ICU mortality RESULTS: Among the 59 patients admitted, 37 (62.7%) patients had initial management in the temporary ICU. They had the same characteristics on admission and the same medical management as patients admitted to the classical ICU. ICU mortality was similar in the 2 groups (32.4% in temporary ICUs versus 40.9% in classical ICUs; p=0.58). SAPS-II and ECMO use were associated with mortality in multivariate analysis but not admission to the temporary ICU. CONCLUSION: In an overload context of the ICU of a geographical area, our temporary ICU model allowed access to intensive care for all patients requiring it without endangering them.

Bacteraemia Is Associated with Increased ICU Mortality in the Postoperative Course of Lung Transplantation.

We aimed to describe the prevalence, risk factors, morbidity and mortality associated with the occurrence of bacteraemia during the postoperative ICU stay after lung transplantation (LT). We conducted a retrospective single-centre study that included all consecutive patients who underwent LT between January 2015 and October 2021. We analysed all the blood cultures drawn during the postoperative ICU stay, as well as samples from suspected infectious sources in case of bacteraemia. Forty-six bacteria were isolated from 45 bacteraemic patients in 33/303 (10.9%) patients during the postoperative ICU stay. Staphylococcus aureus (17.8%) was the most frequent bacteria, followed by Pseudomonas aeruginosa (15.6%) and Enterococcus faecium (15.6%). Multidrug-resistant bacteria accounted for 8/46 (17.8%) of the isolates. The most common source of bacteraemia was pneumonia (38.3%). No pre- or intraoperative risk factor for bacteraemia was identified. Recipients who experienced bacteraemia required more renal replacement therapy, invasive mechanical ventilation, norepinephrine support, tracheotomy and more days of hospitalization during the ICU stay. After adjustment for age, sex, type of LT procedure and the need for intraoperative ECMO, the occurrence of bacteraemia was associated with a higher mortality rate in the ICU (aOR = 3.55, 95% CI [1.56-8.08], p = 0.003). Bacteraemia is a major source of concern for lung transplant recipients.

Personalized risk predictor for acute cellular rejection in lung transplant using soluble CD31.

We evaluated the contribution of artificial intelligence in predicting the risk of acute cellular rejection (ACR) using early plasma levels of soluble CD31 (sCD31) in combination with recipient haematosis, which was measured by the ratio of arterial oxygen partial pressure to fractional oxygen inspired (PaO2/FiO2) and respiratory SOFA (Sequential Organ Failure Assessment) within 3 days of lung transplantation (LTx). CD31 is expressed on endothelial cells, leukocytes and platelets and acts as a "peace-maker" at the blood/vessel interface. Upon nonspecific activation, CD31 can be cleaved, released, and detected in the plasma (sCD31). The study included 40 lung transplant recipients, seven (17.5%) of whom experienced ACR. We modelled the plasma levels of sCD31 as a nonlinear dependent variable of the PaO2/FiO2 and respiratory SOFA over time using multivariate and multimodal models. A deep convolutional network classified the time series models of each individual associated with the risk of ACR to each individual in the cohort.

Favorable, arduous or fatal postoperative pathway within 90 days of lung transplantation.

INTRODUCTION: The maximum gain in quality of life after lung transplantation (LT) is expected between six months and one year after LT, as the occurrence of chronic lung allograft dysfunction may mask the beneficial effects beyond one year. Thus, the postoperative period could be the cornerstone of graft success. We sought to describe the factors present before postoperative admission to the ICU and associated with favorable, arduous or fatal pathway within 90 days of LT. MATERIALS AND METHODS: We conducted a retrospective single-center study between January 2015 and December 2020. Using multinomial regression, we assessed the demographic, preoperative and intraoperative characteristics of patients associated with favorable (duration of postoperative mechanical ventilation < 3 days and alive at Day 90), arduous (duration of postoperative mechanical ventilation ≥ 3 days and alive at Day 90) or fatal (dead at Day 90) pathway within 90 days of LT. RESULTS: A total of 269 lung transplant patients were analyzed. Maximum graft cold ischemic time ≥ 6 h and intraoperative blood transfusion ≥ 3 packed red blood cells were associated with arduous and fatal pathway at Day 90, whereas intraoperative ECMO was strongly associated with fatal pathway. CONCLUSION: No patient demographics influenced the postoperative pathway at Day 90. Only extrinsic factors involving graft ischemia time, intraoperative transfusion, and intraoperative ECMO determined early postoperative pathway.

Relationship between liver dysfunction, lipoprotein concentration and mortality during sepsis.

BACKGROUND: High-density lipoproteins (HDLs) are synthesized by the liver and display endothelioprotective properties, including anti-inflammatory, antiapoptotic, antithrombotic and antioxidant effects. In both septic and chronic liver failure patients, a low HDL cholesterol (HDL-C) concentration is associated with overmortality. Whereas sepsis-associated liver dysfunction is poorly defined, the aim of this study was to characterize the relationship between liver dysfunction, lipoprotein concentrations and mortality in septic patients in the intensive care unit (ICU). METHODS: A prospective observational study was conducted in a university hospital ICU. All consecutive patients admitted for septic shock or sepsis were included. Total cholesterol, HDL-C, low-density lipoprotein-cholesterol (LDL-C), and triglyceride levels were assessed at admission. Sepsis-associated liver dysfunction was defined as a serum bilirubin≥ 2N or aspartate aminotransferase/alanine aminotransferase concentrations ≥ 2N. Short-term and one-year prognostic outcomes were prospectively assessed. RESULTS: A total of 219 septic patients were included, and 15% of them presented with sepsis-associated liver dysfunction at admission. Low concentrations of lipoproteins were associated with mortality at Day 28 in the overall population. Sepsis-associated liver dysfunction at admission was associated with overmortality. In this subgroup, patients had a lower HDL-C concentration than patients without hepatic dysfunction (HDL-C = 0.31 [0.25, 0.55] mmol/L vs. 0.48 [0.29, 0.73] mmol/L, p = 0.0079) but there was no relationship with the outcome. Interestingly, no correlation was observed between lipoprotein concentrations and liver dysfunction markers. CONCLUSION: Sepsis-associated liver dysfunction at ICU admission is strongly associated with overmortality and is associated with a lower HDL-C concentration. However, in this subgroup of patients, HDL-C concentration had no relationship with mortality. Further exploratory studies are needed to better understand the interaction between lipoproteins and liver dysfunction during sepsis.

Massive intraoperative red blood cell transfusion during lung transplantation is strongly associated with 90-day mortality.

BACKGROUND: The effect of red blood cell (RBC) transfusion on mortality after lung transplantation (LT) was assessed in some retrospective studies, with contradictory results. The first aim of this study was to assess the 90-day survival of LT recipients according to massive intraoperative transfusion (MIOT). METHODS: This prospective, observational, single-centre study analysed the intraoperative transfusion (IOT) of all consecutive LT recipients between January 2016 and February 2019. MIOT was defined as transfusion of 5 RBC units or more. The results are presented as the median [IQR] and absolute numbers (proportions) and were analysed using χ2, Fisher, and Mann-Whitney tests (p < 0.05 as significance). Multivariate analyses were performed to identify independent risk factors for MIOT, 90-day and one-year mortality and grade 3 PGD at day 3. Ninety-day and one-year survivals were studied (Kaplan-Meier curves, log rank test). The Paris-North-Hospitals Institutional Review Board approved the study. RESULTS: Overall, 147 patients were included in the analysis, 27 (18%) of them received MIOT. In multivariate analysis, predictive factors of MIOT included preoperative ECMO support (p = 0.017), and bilateral LT (p = 0.023). The SOFA score on ICU admission after LT was higher in cases with MIOT (p < 0.001). MIOT was an independent risk factor for 90-days and one-year mortality (p = 0.002 and 0.008 respectively). The number of RBCs unit transfused during surgery was an independent risk factor for grade 3 PGD at day 3 (OR 1.14, 95% CI [1.00-1.29], p = 0.040). CONCLUSION: Increased preoperative severity of recipients predicts MIOT. MIOT is associated with increased early postoperative morbidity and mortality rates.

Secondary Prophylaxis With Inhaled Colistin to Prevent Recurrence of Pseudomonas aeruginosa and Extended-spectrum ß-lactamase-producing Enterobacterales Pneumonia in ICU After Lung Transplantation: A Before-and-after Retrospective Cohort Analysis.

BACKGROUND: Early pneumonia is an independent risk factor for 1-y mortality after lung transplantation (LTx). Pseudomonas aeruginosa is the most common isolate in early pneumonia and is also associated with an increased risk of chronic lung allograft dysfunction. The aim of our study was to evaluate the efficacy of secondary prophylaxis with inhaled colistin (IC) in preventing the recurrence of P aeruginosa or extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) pneumonia in the postoperative period in the intensive care unit after LTx. METHODS: We conducted a before-and-after retrospective cohort study by including all patients who underwent LTx between January 2015 and December 2020 in our center. Secondary prophylaxis with IC was instituted in January 2018 (observation period from January 2015 to December 2017, intervention period from January 2018 to December 2020). RESULTS: A total of 271 lung transplants were included (125 in the observation period and 146 in the intervention period). The patients were predominately male (64.2%) with a median age of 57 y and received double LTx (67.9%) for chronic obstructive pulmonary disease/emphysema (36.2%) or interstitial lung disease (48.3%). The proportion of patients who experienced at least 1 recurrence of P aeruginosa or ESBL-PE pneumonia was significantly lower in the intervention period than in the observation period (0.7% versus 7.2%, P = 0.007). CONCLUSIONS: Our study suggests a potential benefit of secondary prophylaxis with IC to prevent the recurrence of P aeruginosa or ESBL-PE pneumonia in the intensive care unit after LTx.

Economic impact of an outbreak of carbapenemase producing-Enterobacteriaceae in a surgical intensive care unit.

BACKGROUND: A 15-month outbreak of carbapenemase-producing Enterobacterales (CPE) occurred in the surgical intensive care unit (SICU) of our institution. We aimed to estimate the financial impact of this outbreak from the perspective of the French public health insurance system. METHODS: The characteristics of the colonised/infected CPE patients and outbreak management according to French national guidelines were prospectively collected. Loss of productivity was assessed in terms of the reduction in total number of admissions (TNA) and discharges and in ICU length of stay (LoS). The additional financial burden associated with this outbreak was estimated by the accounting department of the hospital, including the impact of the extended LoS and restricted admissions. RESULTS: Sixteen CPE patients (19 stays) were hospitalised in the SICU (10/2016-01/2018). The median ICU LoS for the CPE cases was 17 [8-36] days versus 6.5 and 6.1 days in 2016 and 2017, respectively, for the whole SICU population. The total number of lost bed days during the outbreak was 452. The TNA dropped dramatically in 2017 (decrease of 20.6%). The estimated costs were 768,386 EUR for bed days lost; 297,176 EUR and 63,675 EUR for the extended LoS for the CPE cases and the patients on contact precautions, respectively; 34,045 EUR for staff reinforcements; 85,764 EUR for bacteriological screening tests; and 42,857 EUR for antimicrobial treatment. The total financial burden of the outbreak was 1,291,903 EUR. CONCLUSION: Management of a CPE outbreak in the SICU is associated with a huge financial burden for the unit and for the institution.

First Recombinant High-Density Lipoprotein Particles Administration in a Severe ICU COVID-19 Patient, a Multi-Omics Exploratory Investigation.

High-density lipoproteins (HDLs) have multiple endothelioprotective properties. During SARS-CoV-2 infection, HDL-cholesterol (HDL-C) concentration is markedly reduced, and studies have described severe impairment of the functionality of HDL particles. Here, we report a multi-omic investigation of the first administration of recombinant HDL (rHDL) particles in a severe COVID-19 patient in an intensive care unit. Plasma ApoA1 increased and HDL-C decreased after each recombinant HDL injection, suggesting that these particles were functional in terms of reverse cholesterol transport. The proportion of large HDL particles also increased after injection of recombinant HDL. Shotgun proteomics performed on HDLs isolated by ultracentrifugation indicated that ApoA1 was more abundant after injections whereas most of the pro-inflammatory proteins identified were less abundant. Assessment of Serum amyloid A-1, inflammatory markers, and cytokines showed a significant decrease for most of them during recombinant HDL infusion. Our results suggest that recombinant HDL infusion is feasible and a potential therapeutic strategy to be explored in COVID-19 patients.

Acute worsening of native lung fibrosis after single lung transplantation for pulmonary fibrosis: two case reports.

BACKGROUND: In patients receiving single lung transplantation for idiopathic pulmonary fibrosis, worsening of fibrosis of the native lung is usually progressive over time, with no significant effects on gas exchange. CASE PRESENTATION: Here, we describe the cases of two Caucasian male recipients of single lung transplants for idiopathic pulmonary fibrosis, 65 and 62 years of age, who exhibited acute worsening of lung fibrosis after an episode of serious viral infection (cytomegalovirus primo-infection in one case and COVID-19 in the other). In both cases, along with opacification of the native lung over several days, the patients presented acute respiratory failure that required the use of high-flow nasal oxygen therapy. Eventually, hypoxemic respiratory failure resolved, but with rapid progression of fibrosis of the native lung. CONCLUSION: We conclude that acute worsening of fibrosis on the native lung secondary to a severe viral infection should be added to the list of potential complications developing on the native lung after single lung transplantation for idiopathic pulmonary fibrosis.