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.

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.

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.

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.

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.

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.

Impact of prior antibiotic therapy on severe necrotizing soft-tissue infections in ICU patients: results from a French retrospective and observational study.

Necrotizing soft-tissue infection (NSTI) is a life-threatening pathology that often requires management in intensive care unit (ICU). Therapies consist of early diagnosis, adequate surgical source control, and antimicrobial therapy. Whereas guidelines underline the need for appropriate routine microbiological cultures before starting antimicrobial therapy in patients with suspected sepsis or septic shock, delaying adequate therapy also strongly increases mortality. The aim of the present study was to compare the characteristics and outcomes of patients hospitalized in ICU for NSTI according to their antimicrobial therapy exposure > 24 h before surgery (called the exposed group) or not (called the unexposed group) before surgical microbiological sampling. We retrospectively included 100 consecutive patients admitted for severe NSTI. The exposed group consisted of 23(23%) patients, while 77(77%) patients belonged to the unexposed group. The demographic and underlying disease conditions were similar between the two groups. Microbiological cultures of surgical samples were positive in 84 patients and negative in 16 patients, including 3/23 (13%) patients and 13/77 (17%) patients in the exposed and unexposed groups, respectively (p = 0.70). The distribution of microorganisms was comparable between the two groups. The main antimicrobial regimens for empiric therapy were also similar, and the proportions of adequacy were comparable (n = 60 (84.5%) in the unexposed group vs. n = 19 (86.4%) in the exposed group, p = 0.482). ICU and hospital lengths of stay and mortality rates were similar between the two groups. In conclusion, in a population of severe ICU NSTI patients, antibiotic exposure before sampling did not impact either culture sample positivity or microbiological findings.

Intensive care readmissions in the first year after lung transplantation: Incidence, early risk factors and outcome.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The initial severity of haemodynamic failure and a prolonged postoperative course seem to be key determinants of ICU readmissions after LT.

Terror in Paris: Incidence and risk factors for infections related to high-energy ammunition injuries.

BACKGROUND: We aimed to assess the incidence and the risk factors for secondary wound infections associated to high-energy ammunition injuries (HEAI) in the cohort of civilian casualties from the 2015 terrorist attacks in Paris. METHODS: This retrospective multi-centric study included casualties presenting at least one HEAI who underwent surgery during the first 48 h following hospital admission. HEAI-associated infection was defined as a wound infection occurring within the initial 30 days following trauma. Risk factors were assessed using univariate and multivariate analysis. RESULTS: Among the 200 included victims, the rate of infected wounds was 11.5%. The median time between admission and the surgical revision for secondary wound infection was 11 days [IQR 9-20]. No patient died from an infectious cause. Infections were polymicrobial in 44% of the cases. The major risk factors for secondary wound infection were ISS (p < 0.001), SAPS II (p < 0.001), MGAP (p < 0.001), haemorrhagic shock (p = 0.003), use of vasopressors (p < 0.001), blood transfusion (p < 0.001), abdominal penetrating trauma (p = 0.003), open fracture (p = 0.01), vascular injury (p = 0.001), duration of surgery (p = 0.009), presence of surgical material (p = 0.01). In the multivariate analysis, the SAPS II score (OR 1.07 [1.014-1.182], p = 0.019) and the duration of surgery (OR 1.005 [1.000-1.012], p = 0.041) were the only risk factors identified. CONCLUSION: We report an 11.5% rate of secondary wound infection following high-energy ammunition injuries. Risk factors were an immediately severe condition and a prolonged surgery.

Dynamic Changes in Microbial Composition During Necrotizing Soft-Tissue Infections in ICU Patients.

Introduction: Recent studies described the threat of emerging multidrug-resistant (MDR) bacteria in intensive care unit (ICU) patients, but few data are available for necrotizing skin and soft tissue infections (NSTI). In a cohort of ICU patients admitted for NSTI, we describe the dynamic changes of microbial population during repeated surgeries. Materials and Methods: This retrospective study compiled consecutive cases admitted for the management of severe NSTI. Clinical characteristics, NSTI features, morbidity and mortality data were collected. The microbiological characteristics of surgical samples obtained during initial surgery were compared with those obtained during the first reoperation, including persistence of initial pathogens and/or emergence of microorganisms. Risk factors for emergence of microorganisms and MDR bacteria were assessed by univariable and multivariable analyses. Results: Among 100 patients {63% male, 58 years old [interquartile ratio (IQR) 50-68]} admitted for NSTI, 54 underwent reoperation with a median [IQR] delay of 3 (1-7) days. Decreased proportions of susceptible strains and emergence of Gram-negative bacteria, including Pseudomonas aeruginosa, staphylococci and enterococci strains, were reported based on the cultures of surgical specimen collected on reoperation. On reoperation, 22 (27%) of the isolated strains were MDR (p < 0.0001 vs. MDR bacteria cultured from the first samples). Broad-spectrum antibiotic therapy as first-line therapy was significantly associated with a decreased emergence of microorganisms. Adequate antibiotic therapy from the initial surgery did not modify the frequency of emergence of microorganisms (p = 0.79) and MDR bacteria (p = 1.0) or the 1-year survival rate. Conclusion: The emergence of microorganisms, including MDR bacteria, is frequently noted in NSTI without affecting mortality.

C4d detection and histological patterns in the diagnosis of antibody-mediated rejection after lung transplantation: a single-centre study.

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+ (<10%), 2+ (10-50%) or 3+ (>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.