Results of Lung Transplantation for Cystic Fibrosis With Selected Donors Over 65 Years Old.

Lung transplantation is limited by the shortage of suitable donors. Many programs have begun to use extended criteria donors. Donors over 65 years old are rarely reported, especially for young cystic fibrosis recipients. This monocentric study was conducted for cystic fibrosis recipients from January 2005 to December 2019, comparing two cohorts according to lung donor age (<65 years or ≥65 years). The primary objective was to assess the survival rate at 3 years using a Cox multivariable model. Of the 356 lung recipients, 326 had donors under 65 years, and 30 had donors over 65 years. Donors' characteristics did not differ significantly in terms of sex, time on mechanical ventilation before retrieval, and partial pressure of arterial oxygen/fraction of inspired oxygen ratio. There were no significant differences in post-operative mechanical ventilation duration and incidence of grade 3 primary graft dysfunction between the two groups. At 1, 3, and 5 years, the percentage of predicted forced expiratory volume in 1 s (p = 0.767) and survival rate did not differ between groups (p = 0.924). The use of lungs from donors over 65 years for cystic fibrosis recipients allows extension of the donor pool without compromising results. Longer follow-up is needed to assess the long-term effects of this practice.

Blood Lactate During Double-Lung Transplantation: A Predictor of Grade-3 Primary Graft Dysfunction.

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

High-Emergency Lung Transplantation for Interstitial Lung Disease Associated With Anti-MDA5 Dermatomyositis: A Case Report.

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

Operating room extubation: A predictive factor for 1-year survival after double-lung transplantation.

BACKGROUND: Operating room (OR) extubation has been reported after lung transplantation (LT) in small cohorts. This study aimed to evaluate the prognosis of OR-extubated patients. The secondary objectives were to evaluate the safety of this approach and to identify its predictive factors. METHODS: This retrospective single-center cohort study included patients undergoing double lung transplantation (DLT) from January 2012 to June 2019. Patients undergoing multiorgan transplantation, repeat transplantation, or cardiopulmonary bypass during the study period were excluded. OR-extubated patients were compared with intensive care unit (ICU)-extubated patients. RESULTS: Among the 450 patients included in the analysis, 161 (35.8%) were extubated in the OR, and 4 were reintubated within 24 hours. Predictive factors for OR extubation were chronic obstructive pulmonary disease (COPD)/emphysema (p = .002) and cystic fibrosis (p = .005), recipient body mass index (p = .048), and the PaO2/FiO2 ratio 10 minutes after second graft implantation (p < .001). OR-extubated patients had a lower prevalence of grade 3 primary graft dysfunction at day 3 (p < .001). Eight (5.0%) patients died within the first year after OR extubation, and 49 (13.5%) patients died after ICU extubation (log-rank test; p = .005). After adjustment for OR extubation predictive factors, the multivariate Cox regression model showed that OR extubation was associated with greater one-year survival (adjusted hazard ratio = 0.40 [0.16-0.91], p = .028). CONCLUSIONS: OR extubation was associated with a favorable prognosis after DLT, but the association should not be interpreted as causality. This fast-track protocol was made possible by a team committed to developing a comprehensive strategy to enhance recovery.

Intraoperative Implications of the Recipients' Disease for Double-Lung Transplantation.

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

Is Extracorporeal Membrane Oxygenation Withdrawal a Safe Option After Double-Lung Transplantation?

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

Prognostic value of the PaO2 /FiO2 ratio determined at the end-surgery stage of a double-lung transplantation.

INTRODUCTION: We evaluated the prognostic role of the arterial oxygen partial pressure/fractional inspired oxygen ratio (PaO2 /FiO2 ratio) measured at the end of double-lung transplantation (DLT). METHODS: This was a monocentric cohort study of all consecutive DLT patients between January 1, 2012, and January 1, 2016, except patients with preoperative extracorporeal membrane oxygenation (ECMO), intraoperative cardiopulmonary bypass, postoperative ECMO, large patent foramen ovale, redo transplantation during the study period, and multiorgan transplantation. RESULTS: A total of 164 patients were included in the study; 45 had a PaO2 /FiO2 ratio <200, 39 a ratio in the range 200-300, and 80 a ratio >300. The risk of being in the lower ratio group is positively related to body mass index, preoperative pulmonary hypertension, and fibrosis. It is negatively related to emergency surgery, age, and intraoperative institution of ECMO. There was a trend for more grade 3 pulmonary graft dysfunction at day 3 in the worst PaO2 /FiO2 ratio group. Mortality at 1000 days was similar for all patients and even after exclusion of patients who had required intraoperative ECMO. CONCLUSION: PaO2 /FiO2 ratio measured at the end of DLT does not forecast 1000-day mortality.

Inhaled nitric oxide dependency at the end of double-lung transplantation: a boosted propensity score cohort analysis.

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

Logistic ex Vivo Lung Perfusion for Hyperimmunized Patients.

Hyperimmunized patients have restricted access to lung transplantation because of the low rate of donor lung availability. Sensitization to human leukocyte antigen is associated with acute rejection, allograft dysfunction, and decreased survival. Prospective crossmatching could allow matching a lung graft with the recipient; however, such a strategy would increase graft ischemia, with a worse impact on the long-term results of lung transplantation. We used logistic ex vivo lung perfusion for 3 patients at the Foch Hospital while waiting for a negative result of the prospective crossmatching and then moved forward to lung transplantation. All patients are alive 3 years after bilateral lung transplantation.

Feasibility and results of a fast-track protocol in thoracic surgery.

BACKGROUND: A rehabilitation program, a multimodal strategy favoring rapid postoperative return to autonomy, has rarely been undertaken after thoracic surgery compared to colectomy. The primary outcome of this fast-track program was the length of postoperative stay. Secondary outcomes concerned the feasibility of this strategy, the incidence of postoperative complications and 3-month postoperative mortality. METHODS: Patients were included in this prospective single-center observational study if they were scheduled for lung resection (lobectomy or wedge resection) performed by posterolateral thoracotomy. The rehabilitation program, coordinated by a referent nurse, included a list of actions to be done, especially early feeding and ambulation, multimodal analgesia including epidural analgesia, early removal of chest tube. RESULTS: One hundred and two patients were included in total with two exclusions (failure of epidural analgesia). The postoperative hospital stay was 8 (7-10) days (median [25-75th percentiles]); this duration was similar to that of the historical cohort which was 9 [7-13] days (P=0.06). Most actions were conducted with a high level of acceptance except for the insertion of a single chest tube (19%) and its removal later than expected in the program. Only 50% of patients left hospital shortly after exit criteria were met suggesting failure in the organization. Patients' satisfaction rate reached 77% and no postoperative death was reported during the follow-up period. CONCLUSION: A program for early rehabilitation is feasible after thoracotomy. Chest drainage and organization to optimize the length of stay are crucial points.

High Emergency Lung Transplantation: dramatic decrease of waiting list death rate without relevant higher post-transplant mortality.

Many candidates for lung transplantation (LT) die on the waiting list, raising the question of graft availability and strategy for organ allocation. We report the experience of the new organ allocation program, "High Emergency Lung Transplantation" (HELT), since its implementation in our center in 2007. Retrospective analysis of 201 lung transplant patients, of whom 37 received HELT from 1st July 2007 to 31th May 2012. HELT candidates had a higher impairment grade on respiratory status and higher Lung Allocation Score (LAS). HELT patients had increased incidence of perioperative complications (e.g., perioperative bleeding) and extracorporeal circulatory assistance (75% vs. 36.6%, P = 0.0005). No significant difference was observed between HELT and non-HELT patients in mechanical ventilation duration (15.5 days vs. 11 days, P = 0.27), intensive care unit length of stay (15 days vs. 10 days, P = 0.22) or survival rate at 12 (81% vs. 80%), and 24 months post-LT (72.9% vs. 75.0%). Lastly, mortality on the waiting list was spectacularly reduced from 19% to 2% when compared to the non-HELT 2004-2007 group. Despite a more severe clinical status of patients on the waiting list, HELT provided similar results to conventional LT. These results were associated with a dramatic reduction in the mortality rate of patients on the waiting list.

Techniques and results of lobar lung transplantations.

OBJECTIVES: We report our experience of lobar lung transplantations (LLTs) in patients with small thoracic volume. METHODS: Since 1988, 50 LLTs were done for cystic fibrosis (n=35), fibrosis (n=7), bronchiectasis (n=3), emphysema (n=3) and lymphangiomyomatosis (n=2). There were 44 females and 6 males (mean age 31±13 years, mean size 155±5.5 cm and mean predicted total lung capacity (TLC) 4463±598 ml). Mean ratio between donor and recipient-predicted TLC was 1.65±0.26. Six patients were listed in high emergency, 2 of them on ECMO as a bridge to transplantation. Forty middle/lower right lobe with left lower LLT, four bilateral lower LLT and six split left lung LLT were performed through a clamshell incision (n=12) or a bilateral antero-lateral thoracotomy (n=38), with epidural analgesia in 17 cases. Thirty-two patients were transplanted under circulatory support (CPB n=16, veno-arterial ECMO n=16). In 11 cases, the right venous anastomosis was enlarged by a pericardial cuff. Ischaemic time was 4.4±1.2 h for the first lobe and 6.1±1.3 h for the second. RESULTS: Median mechanical ventilation weaning time was 10.5 (1-136) days. Four patients were extubated in the operating room. Ten patients needed ECMO for primary graft dysfunction. In-hospital mortality was 28% related to sepsis (n=6), PGD (n=3), haemorrhage (n=2), broncho-vascular fistula (n=1), and multiorgan failure (n=2). Eight patients required endoscopic treatments for airway complications. Mean best FEV1 was 72±16% of the theoretical value. The actuarial 3-year and 5-year survival rates were 60 and 46%, respectively. CONCLUSIONS: LLTs are a reliable solution and can be performed with satisfactory functional results and survival rates.

Scientific evaluation and pricing of medical devices and associated procedures in France.

Medical devices are many and various, ranging from tongue spatulas to implantable or invasive devices and imaging machines; their lifetimes are short, between 18 months and 5 years, due to incessant incremental innovation; and they are operator-dependent: in general, the clinical user performs a fitting procedure (hip implant or pacemaker), a therapeutic procedure using a non-implantable invasive device (arrhythmic site ablation probe, angioplasty balloon, extension spondyloplasty system, etc.) or follow-up of an active implanted device (long-term follow-up of an implanted cardiac defibrillator or of a deep brain stimulator in Parkinson's patients). A round-table held during the XXVIII(th) Giens Workshops meeting focused on the methodology of scientific evaluation of medical devices and the associated procedures with a view to their pricing and financing by the French National Health Insurance system. The working hypothesis was that the available data-set was sufficient for and compatible with scientific evaluation with clinical benefit. Post-registration studies, although contributing to the continuity of assessment, were not dealt with. Moreover, the focus was restricted to devices used in health establishments, where the association between devices and technical medical procedures is optimally representative. An update of the multiple regulatory protocols governing medical devices and procedures is provided. Issues more specifically related to procedures as such, to non-implantable devices and to innovative devices are then dealt with, and the proposals and discussion points raised at the round-table for each of these three areas are presented.