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Corynebacterium spp. are associated with respiratory infections in immunocompromised hosts. A link with bronchial complications after lung transplantation (LTx) has been suggested. We aimed to assess the link between respiratory sampling of Corynebacterium spp. and significant bronchial complication (SBC) after LTx. We performed a single center retrospective study. Inclusion of LTx recipients with at least one respiratory Corynebacterium spp. sample (July 2014 to December 2018). Subjects were matched to unexposed LTx recipients. Primary outcome was SBC occurrence after Corynebacterium spp. isolation. Secondary outcomes were Corynebacterium spp. persistent sampling, chronic lung allograft dysfunction (CLAD) onset and all-cause mortality. Fifty-nine patients with Corynebacterium spp. sampling with 59 without isolation were included. Corynebacterium spp. identification was not associated with SBC occurrence (32.4% vs. 21.6%, p = 0.342). Previous SBC was associated with further isolation of Corynebacterium spp. (OR 3.94, 95% CI [1.72–9.05]). Previous SBC and corticosteroids pulses in the last 3 months were the only factors associated with increased risk of Corynebacterium spp. isolation in multivariate analysis. Corynebacterium spp. sampling was significantly associated with CLAD onset (27.1% vs. 6.9%, p = 0.021). Corynebacterium spp. isolation was not associated with SBC but with higher risk of CLAD. Whether CLAD evolution is affected by Corynebacterium spp. eradication remains to be investigated.

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.

This post-hoc analysis of the AIRFLOW-2 trial investigated the changes in airway CT-parameters after targeted lung denervation (TLD) and whether these changes are associated with treatment response. In the treatment group (n = 32), an improvement in air trapping was significantly associated with an improvement in residual volume (RV). Furthermore, improvements in Pi10 and airway lumen were significantly associated with an improvement in both RV and FEV1. Our results could suggest that when improving airway characteristics like decreasing airway wall thickness and increasing the airway lumen, this leads to less air trapping and an improvement in clinical outcomes.

Background The outcome of lung transplantation (LT) is correlated with donor selection. A donor age of 65 years is classically considered a contraindication to lung procurement, and the results of LT from elderly donors remain to be established. Methods This was a retrospective study of a prospectively maintained database including all LTs performed in a single institution (Bichat Hospital, University of Paris, Paris, France) from January 2014 to March 2019. Donors65 years of age or older were included in the elderly group, whereas donors younger than 65 years of age were included in the control group. Results The study group included 241 LTs, including 44 (18%) in the elderly group and 197 (82%) in the control group. As compared with the control group, the elderly group was characterized by the following: donors of shorter stature (166 cm vs 172 cm; P = .04) and with less smoking history (14% vs 40%; P = .001), less bronchoscopic abnormality (20% vs 36%; P = .042), and less chest opacity (16% vs 30%; P = .048); and recipients of shorter stature (166 cm vs 170 cm; P = .04) but with similar diagnoses and gravity. There was no significant difference between the groups in any of the outcomes studied, including primary graft dysfunction, 30-day mortality, 1-year survival, chronic lung allograft dysfunction–free survival, and overall survival. In univariate analysis, the Oto lung donor score was the only factor associated with 1-year survival (score of 6 in alive patients vs score of 7 in dead patients; P = .04); donor age 65 years old or older was not. Conclusions Carefully selected lung grafts from donors 65 years of age or older are associated with outcomes similar to those reported with grafts from younger donors Grafts from older donors thus provide an interesting option to expand the donor pool during a shortage.

Background A small proportion of patients with chronic obstructive pulmonary disease (COPD) patients present severe pulmonary hypertension (PH), defined by mean pulmonary artery pressure (mPAP) ≥35 mm Hg measured by right heart catheterization. Little is known about the characteristics of severe PH-COPD. The aim of the study based on a national registry was to describe this phenotype. Methods We prospectively included and followed patients with incident PH-COPD. Clinical, functional, hemodynamic data at inclusion and follow-up were retrieved. Survival assessed by Kaplan-Meier analysis was the primary end-point. Results From 2012 to 2016, 99 patients from 13 French centers were included in the study (82 males; median age 66.0 years [interquartile range 62.0-72.0]). At inclusion, most patients had marked dyspnea (55.6% and 22.2% New York Heart Association class III and IV, respectively). During 12 months before inclusion, 42.9% had an exacerbation requiring a hospitalization. Pulmonary function tests showed a moderate obstructive pattern with median (interquartile range) FEV1 50.0 [35.0-63.0] % predicted and low diffusing capacity for carbon monoxide, median 20.0 [16.5-30.6] % predicted. The median values for PaO2 and PaCO2 on room air were 50.0 [44.8-62.0] and 36.0 [31.1-43.0] mm Hg. Median values of mPAP, pulmonary artery occlusion pressure, cardiac index and pulmonary vascular resistance were 42.0 [37.0-48.0] mm Hg, 11.0 [9.0-14.0] mm Hg, 3.0 [2.4-3.6] L/min/m2, and 6.3 [4.2-7.9] WU, respectively. Mean restricted survival was 15.0 [13.9-16.0] months. Conclusions Severe PH-COPD is characterized by moderate airway obstruction but marked dyspnea and marked hypoxemia, low DLCO and high mPAP. This phenotype is associated with poor prognosis.

Background: Bronchoscopic lung volume reduction using endobronchial coils is a new treatment for patients with severe emphysema. To date, the benefits have been modest and have been suggested to be much larger in patients with severe hyperinflation and nonmulti-comorbidity. Objective: We aimed to evaluate the efficacy and safety of endobronchial coil treatment in a randomized multicenter clinical trial using optimized patient selection. Method: Patients with severe emphysema on HRCT scan with severe hyperinflation (residual volume [RV] ≥200% predicted and RV/total lung capacity [TLC] >55%) were randomized to coil treatment or control. Primary outcome measures were differences in the forced expiratory volume in 1 s (FEV1) and St George’s Respiratory Questionnaire (SGRQ) total score at 6 months. Results: Due to premature study termination, a total of 120 patients (age 63 ± 7 years, FEV1 29 ± 7% predicted, RV 251 ± 41% predicted, RV/TLC 67 ± 6%, and SGRQ 58 ± 13 points), instead of 210 patients, were randomized. At study termination, 91 patients (57 coil and 34 control) had 6-month results available. Analyses showed significantly greater improvements in favor of the coil group. The increase in FEV1 was greater in the coil group than that in the control group by + 10.3 [+4.7 to +16.0] % and in SGRQ by −10.6 [−15.9 to −5.4] points. At study termination, there were 5 (6.8%) deaths in the coil cohort reported. Conclusion: Despite early study termination, coil treatment compared to control results in a significant improvement in the lung function and quality of life benefits for up to 6 months in patients with emphysema and severe hyperinflation. These improvements were of clinical importance but were associated with a higher likelihood of serious adverse events.

International audience; Almost 25% of patients with pulmonary fibrosis referred for lung transplantation have a germline rare variant of a telomere-related gene. Acquired TERT promoter mutations may counterbalanced the germline defect and reduce the risk of hematological complications in this population. In a series of 34 patients with a germline telomere-related gene mutation who underwent lung transplantation, 12 (35%) patients had at least 1 acquired TERT promoter mutation. Six patients presented myelodysplasia before lung transplantation, with no difference between patients with and without an acquired TERT promoter mutation. After lung transplantation, myelodysplasia developed in only 1 of 8 patients with an acquired TERT promoter mutation versus 7 of 18 patients without a mutation. Survival did not differ between patients with and without an acquired mutation. The presence of an acquired TERT promoter mutation could be associated with reduced hematological complications after transplantation and with better outcome in telomere-related gene mutation carriers but requires further study. (C) 2022 International Society for Heart and Lung Transplantation.

International audience; Lung transplantation (LTx) is a steadily expanding field. The considerable developments have been driven over the years by indefatigable work conducted at LTx centers to improve donor and recipient selection, combined with multifaceted efforts to overcome challenges raised by the surgical procedure, perioperative care, and long-term medical complications. One consequence has been a pruning away of contraindications over time, which has, in some ways, complicated the patient selection process. The Francophone Pulmonology Society (Société de Pneumology de Langue Française, SPLF) set up a task force to produce up-to-date working guidelines designed to assist pulmonologists in managing end-stage respiratory insufficiency, determining which patients may be eligible for LTx, and appropriately timing LTx-center referral. The task force examined the most recent literature and evaluated the risk factors that limit patient survival after LTx. Ideally, the objectives of LTx are to prolong life while also improving quality of life. The guidelines developed by the task force apply to a limited resource and are consistent with the ethical principles described below.

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 β-lactamase-producing Enterobacterales (ESBL-PE) pneumonia in the postoperative period in the intensive care unit after LTx.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).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).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.

International audience; IPF is a devastating lung disease with limited therapeutic possibilities. FGF19, an endocrine FGF, was recently shown to decrease liver fibrosis. To ask whether FGF19 had anti-fibrotic properties in the lung and decipher its effects on common features associated with lung fibrogenesis. We assessed, by Elisa, FGF19 levels in plasma and bronchoalveolar lavage fluids (BALF)obtained from controls and IPF patients. In vivo, using an intravenously administered adeno11 associated virus (AAV), we overexpressed FGF19 at the fibrotic phase of two experimental models of murine lung fibrosis and assessed its effect on lung morphology, lung collagen content, fibrosis markers and pro fibrotic mediator expression, at mRNA and protein levels. In vitro, we investigated whether FGF19 could modulate the TGFβ-induced differentiation of primary human lung fibroblast into myofibroblast and the apoptosis of murine alveolar type II cell. While FGF19 was not detected in BALF, FGF19 concentration was decreased in the plasma of IPF patients compared to controls. In vivo, the overexpression of FGF19 was associated with a marked decrease of lung fibrosis and fibrosis markers, with a decrease of pro fibrotic mediator expression and lung collagen content. In vitro, FGF19 decreased alveolar type 2 epithelial cell apoptosis through the decrease of the proapoptotic BIM protein expression and prevented TGF-ß induced myofibroblast differentiation through the inhibition of JNK phosphorylation. Altogether these data identify FGF19 as an anti-fibrotic molecule with a potential therapeutic interest in fibrotic lung disorders.

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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).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.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).Increased preoperative severity of recipients predicts MIOT. MIOT is associated with increased early postoperative morbidity and mortality rates.

Although shoulder arthroplasty is relatively safe in general population, it remains unclear in transplant recipient. Aim of this study was to determine outcomes and morbidity after shoulder arthroplasty in lung transplant recipients. A retrospective analysis was performed at our university hospital center from 2001 to 2015. Main inclusion criterion was all lung transplant recipient who underwent shoulder arthroplasty. Clinical outcomes including Constant score, visual analogue scale (VAS), American Shoulder and Elbow Surgeons score (ASES) were determined in pre-operative period and a minimum follow-up of 36 months. Special attention was taken about complications. Among 700 lung transplant recipients, we identified 12 patients who underwent 14 shoulder arthroplasties. Arthroplasties were performed after proximal humeral avascular necrosis (n = 10), degenerative osteoarthritis (n = 1) and non-union of proximal humeral fracture (n = 1). 8 anatomical total shoulder arthroplasties and 6 reversed shoulder arthroplasties were performed. Mean follow-up was 61.4 months (± 22.1). Mean age was 47.1 (± 9.3) years. All patients had immunosuppression therapy at the time of surgery. Mean Constant score was improved at last follow-up [43(± 9.7) vs 94(± 4), p

BACKGROUND Acute kidney injury (AKI) is associated with increased short-term and long-term mortality and morbidity after lung transplantation (LT). The primary objective of this study was to analyze the perioperative factors associated with AKI according to KDIGO criteria during hospitalization in an intensive care unit (ICU) after LT. METHODS This was a single-center observational, prospective study. AKI was defined according to KDIGO criteria. Results are expressed as median, interquartile range, absolute numbers and percentages. Statistical analyses were performed using Chi-square test, Fisher’s exact test and Mann-Witney U test (p 3 days (OR 4.26 95%CI [1.49; 13.63] p=0.010 and OR 5.56 [1.25; 11.47] p=0.018, respectively). AKI and the need for RRT were significantly associated with ICU mortality, 28-day mortality and one-year mortality. CONCLUSION AKI is common during ICU stay after LT, especially after bilateral LT and is associated with prolonged MV, and increased short-term and long-term mortality.

OBJECTIVES In lung transplantation (LT), femoral venoarterial extracorporeal membrane oxygenation (VA-ECMO) usually requires an open approach that may be associated with severe groin wound infection. In endovascular aortic procedures, preclosing of the femoral artery (PFA) with vascular closure devices allows the percutaneous insertion and withdrawal of large-bore cannulae. We sought to evaluate whether this innovative technique could be applied in the specific setting of LT to achieve total percutaneous VA-ECMO and decrease groin wound infection. METHODS We conducted a retrospective study of a prospective database including patients who underwent LT in our centre from January 2011 to December 2017. Patients who underwent peripheral VA-ECMO using the PFA technique after January 2014 (PFA group, n = 106) were compared to those who underwent peripheral VA-ECMO using open cannulation and/or decannulation before January 2014 (non-PFA group, n = 48). The primary end point was the rate of technical success defined as total percutaneous VA-ECMO. Secondary end points included groin wound infections and delayed vascular complications. RESULTS The PFA technique was technically successful in 98 patients (92.5%). As compared with the non-PFA group, the PFA group was characterized by a similar rate of vascular complications (16.6% vs 11.3%, P = 0.360) and a decreased rate of groin wound infection (18.9% vs 0%, P CONCLUSIONS In LT patients, PFA is associated with a high rate of total percutaneous VA-ECMO, thus preventing the occurrence of groin wound infection.

BACKGROUND Restrictive allograft syndrome (RAS) after lung transplantation (LTx) is associated with the poorer graft survival in patients with chronic lung allograft dysfunction (CLAD). Nevertheless, its diagnostic criteria have not been clearly defined after single-LTx (SLTx). Hence, we studied an SLTx cohort with CLAD to investigate the utility of both computed tomography (CT)-score/volume measures and functional spirometric criteria for the early identification of RAS in this population. METHODS We included 51 patients with SLTx (17 RAS, 17 bronchiolitis obliterans syndrome [BOS], and 17 stable condition). The criteria for RAS diagnosis in SLTx included forced vital capacity (FVC) 0.7 and persistent CT-scan-lung opacities. We defined 4 time points (T): T-baseline, T-onset (first CT-scan-opacities), T-follow-up, and T-last. RESULTS In patients with RAS, the spirometric criteria for RAS at T-onset were reached in only 47% (FVC decline 0.7 [41%]), whereas at the same T-onset date, the graft CT-score increased to 5 (4-6) vs 1 (0-2) at baseline (p < 0.001) (CT - score ≥2 at T-onset in 100% and ΔCT - score ≥2 in 74% of patients with RAS), and the median CT-scan graft volume decreased to 1,722 ml (vs 1,796 ml at T-baseline, p = 0.003) (decreased CT-graft - volume

BACKGROUND AND PURPOSE: In patients with pulmonary hypertension (PH) associated with lung disease and/or hypoxia (Group III), decreased pulmonary vascular tone and tissue hypoxia is therapeutically beneficial. PGE(2) and PGI(2) induce potent relaxation of human bronchi from non‐PH (control) patients via EP(4) and IP receptors, respectively. However, the effects of PGE(2)/PGI(2) and their mimetics on human bronchi from PH patients are unknown. Here, we have compared relaxant effects of several PGI(2)–mimetics approved for treating PH Group I with several PGE(2)–mimetics, in bronchial preparations derived from PH Group III and control patients. EXPERIMENTAL APPROACH: Relaxation of bronchial muscle was assessed in samples isolated from control and PH Group III patients. Expression of prostanoid receptors was analysed by western blot and real‐time PCR, and endogenous PGE(2), PGI(2), and cAMP levels were determined by ELISA. KEY RESULTS: Maximal relaxations induced by different EP(4) receptor agonists (PGE(2), L‐902688, and ONO‐AE1‐329) were decreased in human bronchi from PH patients, compared with controls. However, maximal relaxations produced by PGI(2)–mimetics (iloprost, treprostinil, and beraprost) were similar for both groups of patients. Both EP(4) and IP receptor protein and mRNA expressions were significantly lower in human bronchi from PH patients. cAMP levels significantly correlated with PGI(2) but not with PGE(2) levels. CONCLUSION AND IMPLICATIONS: The PGI(2)–mimetics retained maximal bronchodilation in PH Group III patients, whereas bronchodilation induced by EP(4) receptor agonists was decreased. Restoration of EP(4) receptor expression in airways of PH Group III patients with respiratory diseases could bring additional therapeutic benefit.

Patient-important outcomes (PIOs) have emerged in respiratory medicine, in order to place the patient at the center of research. Mortality is a debated PIO in lung transplantation (LTx). The use of PIO in this specific setting has never been studied. We aimed to systematically review the use of PIOs in LTx research.MEDLINE, Cochrane Library and Embase databases were searched to include prospective studies published in 2019, involving adult LTx recipients. We excluded articles reporting non-prognostic studies, letters, reviews, commentaries, or case reports. PIOs considered were mortality, pain, physical function, pulmonary, gastrointestinal, neuropsychological, cardiac, sleep or sexual symptoms and quality of life. This systematic review was prospectively registered in the PROSPERO register (CRD42020163425).Among 1048 references retrieved, 51 were finally included in the analysis. In total, 26 (51%) studies investigated at least one PIO, as a primary outcome in 12 (23.5%) and secondary outcome in 21 (41.2%). In 15 (29.4%) studies, mortality was the most frequently reported PIO; 11 (21.5%) studies evaluated at least one PIO other than mortality, quality of life being this PIO in 6.PIOs were described in half of prospective articles dealing with adult LTx recipients published in 2019. Outcomes other than mortality were insufficiently considered. A core outcome set of PIOs in LTx should be developed with patient input to guide future research in LTx.

Poly(A)-specific ribonuclease (PARN) mutations have been associated with familial pulmonary fibrosis. This study aims to describe the phenotype of patients with interstitial lung disease (ILD) and heterozygous PARN mutations.We performed a retrospective, observational, non-interventional study of patients with an ILD diagnosis and a pathogenic heterozygous PARN mutation followed up in a centre of the OrphaLung network.We included 31 patients (29 from 16 kindreds and two sporadic patients). The median age at ILD diagnosis was 59 years (range 54 to 63). In total, 23 (74%) patients had a smoking history and/or fibrogenic exposure. The pulmonary phenotypes were heterogenous, but the most frequent diagnosis was idiopathic pulmonary fibrosis (n = 12, 39%). Haematological abnormalities were identified in three patients and liver disease in two. In total, 21 patients received a specific treatment for ILD: steroids (n = 13), antifibrotic agents (n = 11), immunosuppressants (n = 5) and N-acetyl cysteine (n = 2). The median forced vital capacity decline for the whole sample was 256 ml/year (range -363 to -148). After a median follow-up of 32 months (range 18 to 66), 10 patients had died and six had undergone lung transplantation. The median transplantation-free survival was 54 months (95% CI 29 to ∞). Extra-pulmonary features were less frequent with PARN mutation than telomerase reverse transcriptase (TERT) or telomerase RNA component (TERC) mutation.IPF is common among individuals with PARN mutation, but other ILD subtypes may be observed.

BACKGROUND The first aim of this study was to assess the association between stage 3 PGD and pre-donation blood transfusion of the donor. The secondary objectives were to assess the epidemiology of donor transfusion and the outcome of LT recipients according to donor transfusion status and massive donor transfusion status. METHODS This was an observational, prospective, single-center study. The results are expressed as absolute numbers, percentages, medians, and interquartile ranges. Statistical analyses were performed using Chi squared, Fischer's exact tests, and Mann-Whitney U tests (P

AIMS Antibody-mediated rejection (AMR) is an emerging and challenging issue in transplantation. Endothelial deposition of C4d and microvascular inflammation (MI) are reliable markers of AMR in renal and cardiac transplantation, but remain controversial in the lung. Our aim was to assess C4d immunohistochemistry and histological patterns for the diagnosis of lung AMR. METHODS AND RESULTS We reviewed 158 transbronchial biopsies (TBBs) (n = 85 clinically indicated, and n = 73 surveillance TBBs) from 48 recipients, blinded to clinical and serological data. C4d was scored as 0, 1+ ( 50%). TBBs were reassessed for MI and acute lung injury (ALI). Donor-specific antibodies (DSAs), acute clinical graft dysfunction and chronic lung allograft graft dysfunction (CLAD) were recorded. C4d3+, C4d2+, C4d1+ and C4d0 occurred respectively in four (2.5%), six (3.8%), 28 (17.7%) and 120 (75.9%) TBBs. MI and ALI were rare but more frequent in C4d1-3+ TBBs than in the absence of C4d. C4d2+ was frequently observed with concomitant infection. Among the surveillance TBBs, only two (2.7%) showed MI. Neither ALI nor C4d3+ was diagnosed on surveillance TBBs. No significant association was found between histopathological findings and DSAs. All four patients with C4d3+ could retrospectively be diagnosed with AMR and developed CLAD. CONCLUSION Although rare, diffuse C4d deposition appears to be a strong indication of acute clinical AMR in lung transplant patients, whereas intermediate C4d2+ requires more investigations. In stable patients, histopathology and C4d may lack the sensitivity to diagnose subclinical AMR. This emphasises the need for a multidisciplinary evaluation of each suspected AMR case, and the need for complementary diagnostic tools.

Background Hepatopulmonary syndrome (HPS) is characterized by an arterial oxygenation defect, defined by an increased alveolar-arterial oxygen gradient, induced by pulmonary vascular dilatations in the context of liver disease. The pathogenesis of HPS is poorly understood. Morphologic changes associated with HPS are unknown. This study aimed at describing imaging and pathology changes associated with HPS. Methods We performed a case-control study in candidates for transplant with suspicion of cirrhosis. Each patient with HPS (Pao2 ≤ 70 mm Hg) was matched to three control subjects for age, cause, and liver disease severity. Pretransplant thoracic and abdominal imaging and explanted livers were reviewed. Results CT scans and Doppler ultrasounds from 21 patients with HPS were compared with those from 63 control subjects. HPS was associated with a two- to threefold higher prevalence of obstructed intrahepatic portal branches, of slowed or hepatofugal portal blood flow, and of large abdominal portosystemic shunts. Hepatic artery diameter was also larger in patients with HPS. Explanted livers from 19 patients with HPS were compared with those from 57 control subjects. HPS was associated with a fourfold higher prevalence of portal venule thrombosis and a ninefold higher prevalence of extensive vascular proliferation within fibrous septa. Obstruction of centrilobular venules, sinusoidal dilatation, and liver parenchymal extinction were also more common in patients with HPS. Conclusions HPS is associated with intrahepatic vascular changes and with features suggesting severe portal hypertension. These results raise the hypothesis that intrahepatic vascular changes precipitate the development of HPS, opening new therapeutic perspectives for HPS.

Predictive factors of intensive care readmissions after lung transplantation (LT) have not been established. The main objective of this study was to assess early risk factors for ICU readmission during the first year after LT.This retrospective, observational, single-centre study included all consecutive patients who underwent LT in our institution between January 2016 and November 2019. Patients who died during the initial hospitalisation in the ICU were excluded. Surgical and medical ICU readmissions were collected during the first year. The results are expressed as medians, interquartile ranges, absolute numbers and percentages. Statistical analyses were performed using the chi-square test, Fisher's exact test and Mann-Whitney U test as appropriate (p 0.05 as significance). Multivariate analysis was performed to identify independent risk factors for readmission. The Paris-North-Hospitals Institutional Review Board reviewed and approved the study.A total of 156 patients were analysed. Eighteen of them (12%) died during the initial ICU hospitalisation. During the first year after LT, ICU readmission was observed for 49/138 (36%) patients. Among these patients, 14/49 (29%) died during the study period. Readmission was mainly related to respiratory failure (35 (71%) patients), infectious diseases (28 (57%) patients), airway complications (11 (22%) patients), and immunologic complications (4 (8%) patients). In the multivariate analysis, ICU readmission was associated with the use of high doses of catecholamines during surgery, and the increased duration of initial ICU stay.The initial severity of haemodynamic failure and a prolonged postoperative course seem to be key determinants of ICU readmissions after LT.

Matrix remodeling is a salient feature of idiopathic pulmonary fibrosis (IPF). Targeting cells driving matrix production and remodeling could be a promising avenue for IPF treatment. Analysis of public transcriptomic database identified paired-related homeobox protein-1 (PRRX1) as an upregulated mesenchymal transcription factor (TF) in IPF. We confirmed that PRRX1 isoforms were upregulated in IPF lung tissue and strongly expressed by lung fibroblasts. In vitro, PRRX1 expression was up-regulated by cues associated with proliferative and anti-fibrotic properties in lung fibroblasts, while IPF fibroblast-derived matrix increased PRRX1 TFs expression in a PDGFR dependent manner in control ones. Meanwhile, signals promoting myofibroblastic differentiation decreased PRRX1 TF. We demonstrated that PRRX1 inhibition decreased fibroblast proliferation by downregulating the expression of S phase cyclins. PRRX1 inhibition also impacted TGF-{beta} driven myofibroblastic differentiation by inhibiting SMAD2/3 phosphorylation through phosphatase PPM1A upregulation and TGFBR2 downregulation, leading to a TGF-{beta} response global decrease. Finally, targeted inhibition of Prrx1 TFs attenuated fibrotic remodeling both in vivo with intra-tracheal antisense oligonucleotides in the bleomycin mice model of lung fibrosis and ex vivo using mouse and Human precision-cut lung slices stimulated with fibrosis cytokine cocktail. Altogether, our results identified PRRX1 as a mesenchymal transcription factor driving myofibroblastic phenotype and lung fibrogenesis. Brief SummaryInhibition of a single fibroblast-associated transcription factor, namely paired-related homeobox protein 1, is sufficient to dampen lung fibrogenesis.

Resume Introduction Le nombre des transplantations pulmonaires realisees dans le monde n’a cesse d’augmenter au fil du temps. A mesure de l’experience accumulee, l’âge est passe d’une contre-indication absolue a une contre-indication relative. Nous rapportons ici notre premiere experience avec les receveurs âges de 65 ans et plus. Methodes Toutes les transplantations pulmonaires entre janvier 2014 et mars 2019 chez les patients âges de 65 ans et plus ont ete retrospectivement analysees a partir d’une base de donnees prospective. Resultats Vingt-cinq patients âges de 65 ans et plus ont ete transplantes durant la periode de l'etude parmi les 241 patients transplantes a l'hopital Bichat (Paris). Les indications etaient les pathologies interstitielles (72 %) et les troubles ventilatoires obstructifs (28 %). Les transplantations etaient mono-pulmonaires dans 80 % des cas. Seize patients ont necessite une assistance circulatoire par ECMO veino-arterielle peripherique en peroperatoire. Les complications precoces ont ete dominees par la defaillance primaire du greffon grade 3 (12 %) et le rejet cellulaire (20 %). La survie globale a un an a ete de 76 %. Conclusion Les resultats precoces de cette courte serie monocentrique et retrospective sont encourageants et nous permettent de continuer a proposer l’acces a la transplantation chez les patients âges de 65 ans et plus sous reserve d’une selection rigoureuse.

We thank Yan VC and Muller FL (1) for taking their valuable time to comment on our article.….

SARS‐Cov2 outbreak has deeply impacted French lung transplant programs by the decreased number of lung donors, the scarcity of intensive care unit (ICU) beds and most importantly, the assumed worse prognosis of Covid‐19 in recipients during perioperative period. Despite no evidence has been published to suggest that lung transplant recipients were at high‐risk of acquiring the virus or developing severe Covid‐19, immunosuppression may worsen the prognosis of such infection in patient transplanted for end‐staged lung diseases.

Objective To evaluate the clinical course of and risk factors for arterial thrombotic events in adult inpatients with coronavirus disease 2019 (COVID-19). Methods All consecutive adult patients admitted for COVID-19 infection in a referral center in France and discharged from the hospital between April 1 and April 30, 2020, were included. All arterial thrombotic events that occurred through discharge were considered for analysis. Epidemiologic, demographic, clinical, laboratory, treatment, and outcome data were extracted from electronic medical records with use of a standardized data collection form. Results Overall, 531 COVID-19+ patients were analyzed. Among them, 30 (5.6%) experienced arterial thrombotic events. Arterial thrombotic events in the setting of COVID-19 infection happened at a median of 11 (5-20) days after the first symptoms of infection; occurred in high-risk patients according to traditional cardiovascular risk factors; had an atypical pattern, such as thrombosis of the aorta, upper limb, or renal arteries or cerebral microvasculopathy in 7 (23.3%) cases; and were associated with an in-hospital mortality rate of 40%. Arterial thrombotic events increased the risk of death by 3-fold in COVID-19+ patients (hazard ratio, 2.96; 95% CI, 1.4 to 4.7; P=.002). A subdistribution survival hazard model showed that a concentration of D-dimer above 1250 ng/mL increased the risk of arterial thrombotic events in COVID-19+ patients by more than 7 (subdistribution hazard ratio, 7.68; 95% CI, 2.9 to 20.6; P Conclusion A dramatically high rate of in-hospital death was observed in patients who suffered arterial thrombotic events in the setting of COVID-19 infection. A D-dimer level above 1250 ng/mL at entry may identify COVID-19+ patients at risk for arterial thrombotic events.