Circulating cell-free and extracellular vesicles-derived microRNA as prognostic biomarkers in patients with early-stage NSCLC: results from RESTING study.

BACKGROUND: Factors to accurately stratify patients with early-stage non-small cell lung cancer (NSCLC) in different prognostic groups are still needed. This study aims to investigate 1) the prognostic potential of circulating cell-free (CF) and extracellular vesicles (EVs)-derived microRNA (miRNAs), and 2) their added value with respect to known prognostic factors (PFs). METHODS: The RESTING study is a multicentre prospective observational cohort study on resected stage IA-IIIA patients with NSCLC. The primary end-point was disease-free survival (DFS), and the main analyses were carried out separately for CF- and EV-miRNAs. CF- and EV-miRNAs were isolated from plasma, and miRNA-specific libraries were prepared and sequenced. To reach the study aims, three statistical models were specified: one using the miRNA data only (Model 1); one using both miRNAs and known PFs (age, gender, and pathological stage) (Model 2), and one using the PFs alone (Model 3). Five-fold cross-validation (CV) was used to assess the predictive performance of each. Standard Cox regression and elastic net regularized Cox regression were used. RESULTS: A total of 222 patients were enrolled. The median follow-up time was 26.3 (95% CI 25.4-27.6) months. From Model 1, three CF-miRNAs and 21 EV-miRNAs were associated with DFS. In Model 2, two CF-miRNAs (miR-29c-3p and miR-877-3p) and five EV-miRNAs (miR-181a-2-3p, miR-182-5p, miR-192-5p, miR-532-3p and miR-589-5p) remained associated with DFS. From pathway enrichment analysis, TGF-beta and NOTCH were the most involved pathways. CONCLUSION: This study identified promising prognostic CF- and EV-miRNAs that could be used as a non-invasive, cost-effective tool to aid clinical decision-making. However, further evaluation of the obtained miRNAs in an external cohort of patients is warranted.

One-Year Mortality After Lung Transplantation: Experience of a Single French Center Between 2012 and 2021.

BACKGROUND Lung transplantation (LTx) is a life-extending therapy for specific patients with terminal lung diseases. This study aimed to evaluate the associations and causes of 1-year mortality after lung transplantation at Strasbourg University Hospital, France, between 2012 and 2021. MATERIAL AND METHODS We carried out a retrospective analysis on 425 patients who underwent LTx at Strasbourg University Hospital between January 1, 2012, and December 31, 2021. Pre-transplant, perioperative, and postoperative data were collected from the electronic medical records. RESULTS Among all patients, 94.6% had a LTx, 4.0% a heart-lung transplantation, and 1.4% underwent pancreatic islet-lung transplantation. The median age at transplantation was 57 years, with 55.3% male patients. The main native lung disease leading to LTx was chronic obstructive pulmonary disease in 51.1% of patients; 16.2% needed super-urgent LTx. The 1-year mortality rate was 11.5%. Most deaths were either caused by multi-organ failure or septic shock. In our multivariate analysis, we identified 3 risk factors significantly related to 1-year mortality after LTx: body mass index (BMI) between 25 and 30 kg/m² vs BMI between 18.5 and 25 kg/m² (P=0.032), postoperative extracorporeal membrane oxygenation support (P=0.034), and intensive care unit length of stay after transplantation (P<0.001). Two other factors were associated with a significantly lower 1-year mortality risk: longer hospital stay after LTx (P=0.024) and tacrolimus prescription (P=0.004). CONCLUSIONS Our study reported a 1-year mortality rate of 11.5% after LTx. Although LTx candidates are carefully selected, additional data are required to improve understanding of the risk factors for post-LTx mortality.

Real-world outcomes of lobectomy, segmentectomy and wedge resection for the treatment of stage c-IA lung carcinoma.

OBJECTIVES: To determine safety and survival outcomes associated with lobectomy, segmentectomy and wedge resection for early-stage lung cancer by quiring the French population-based registry EPIdemiology in THORacic surgery (EPITHOR). METHODS: Retrospective analysis of 19 452 patients with stage c IA lung carcinoma who underwent lobectomy, segmentectomy or wedge resection between 2016 and 2022 with curative-intent. Main outcome measures were 90-day mortality and 5-year overall survival estimates. Proportional hazards regression and propensity score matching were used to adjust outcomes for key patient, tumour and practice environment factors. RESULTS: The treatment distribution was 72.2% for lobectomy, 21.5% for segmentectomy and 6.3% for wedge. Unadjusted 90-day mortality rates were 1.6%, 1.2% and 1.1%, respectively (P = 0.10). Unadjusted 5-year overall survival estimates were 80%, 78% and 70%, with significant inter-group survival curves differences (P < 0.0001). Multivariable proportional hazards regression showed that wedge was associated with worse overall survival [adjusted hazard ratio (AHR), 1.23 (95% confidence interval 1.03-1.47); P = 0.021] compared with lobectomy, while no significant difference was disclosed when comparing segmentectomy to lobectomy (1.08 [0.97-1.20]; P = 0.162). The three-way propensity score analyses confirmed similar 90-day mortality rate for wedge resection and segmentectomy compared with lobectomy (hazard ratio: 0.43; 95% confidence interval 0.16-1.11; P = 0.081 and 0.99; 0.48-2.10; P = 0.998, respectively), but poorer overall survival (1.45; 1.13-1.86; P = 0.003 and 1.31; 1-1.71; P = 0.048, respectively). CONCLUSIONS: Wedge resection was associated with comparable 90-day mortality but lower overall survival when compared to lobectomy. Overall, all types of sublobar resections may not offer equivalent oncologic effectiveness in real-world settings.

Survival outcomes following urgent lung transplantation in France and the USA.

INTRODUCTION: Lung graft allocation can be based on a score (Lung Allocation Score) as in the USA or sequential proposals combined with a discrete priority model as in France. We aimed to analyse the impact of allocation policy on the outcome of urgent lung transplantation (LT). METHODS: US United Network for Organ Sharing (UNOS) and French Cristal databases were retrospectively reviewed to analyse LT performed between 2007 and 2017. We analysed the mortality risk of urgent LT by fitting Cox models and adjusted Restricted Mean Survival Time. We then compared the outcome after urgent LT in the UNOS and Cristal groups using a propensity score matching. RESULTS: After exclusion of patients with chronic obstructive pulmonary disease/emphysema and redo LT, 3775 and 12 561 patients underwent urgent LT and non-urgent LT in the USA while 600 and 2071 patients underwent urgent LT and non-urgent LT in France. In univariate analysis, urgent LT was associated with an HR for death of 1.24 (95% CI 1.05 to 1.48) in the Cristal group and 1.12 (95% CI 1.05 to 1.19) in the UNOS group. In multivariate analysis, the effect of urgent LT was attenuated and no longer statistically significant in the Cristal database (HR 1.1 (95% CI 0.91 to 1.33)) while it remained constant and statistically significant in the UNOS database (HR 1.12 (95% CI 1.05 to 1.2)). Survival comparison of urgent LT patients between the two countries was significantly different in favour of the UNOS group (1-year survival rates 84.1% (80.9%-87.3%) vs 75.4% (71.8%-79.1%) and 3-year survival rates 66.3% (61.9%-71.1%) vs 62.7% (58.5%-67.1%), respectively). CONCLUSION: Urgent LT is associated with adverse outcome in the USA and in France with a better prognosis in the US score-based system taking post-transplant survival into account. This difference between two healthcare systems is multifactorial.

Infectious Mediastinitis: A Retrospective Cohort Study.

Background: This study aimed to characterize the demographics, microbiology, management and treatment outcomes of mediastinitis according to the origin of the infection. Methods: This retrospective observational study enrolled patients who had mediastinitis diagnosed according to the criteria defined by the Centers for Disease Control and Prevention and were treated in Strasbourg University Hospital, France, between 1 January 2010 and 31 December 2020. Results: We investigated 151 cases, including 63 cases of poststernotomy mediastinitis (PSM), 60 cases of mediastinitis due to esophageal perforation (MEP) and 17 cases of descending necrotizing mediastinitis (DNM). The mean patient age (standard deviation) was 63 (14.5) years, and 109 of 151 patients were male. Microbiological documentation varied according to the origin of the infection. When documented, PSM cases were mostly monomicrobial (36 of 53 cases [67.9%]) and involved staphylococci (36 of 53 [67.9%]), whereas MEP and DNM cases were mostly plurimicrobial (38 of 48 [79.2%] and 8 of 12 [66.7%], respectively) and involved digestive or oral flora microorganisms, respectively. The median duration of anti-infective treatment was 41 days (interquartile range, 21-56 days), and 122 of 151 patients (80.8%) benefited from early surgical management. The overall 1-year survival rate was estimated to be 64.8% (95% confidence interval, 56.6%-74.3%), but varied from 80.1% for DNM to 61.5% for MEP. Conclusions: Mediastinitis represents a rare yet deadly infection. The present cohort study exhibited the different patterns observed according to the origin of the infection. Greater insight and knowledge on these differences may help guide the management of these complex infections, especially with respect to empirical anti-infective treatments.

Impact of the COVID-19 pandemic on lung transplant patients and on a cohort of patients with rare lung disease: A single-center study.

INTRODUCTION: Due to the COVID-19 pandemic, France underwent several lockdown periods during 2020. Our aim was to evaluate its clinical and social impact on lung transplant (LT) patients treated at Strasbourg University Hospital, by comparing three periods: first lockdown (T1: March-May 2020), end of the first lockdown (T2: May-October 2020), and second lockdown (T3: November-December 2020) and the incidence of COVID-19 infections. A cohort of patients with rare lung disease (RLD) was also studied during T2. METHODS: We used clinical and paraclinical data collected during routine follow-up. A questionnaire was submitted to each patient at each period to assess their lifestyle, adherence to protective measures against COVID-19, contacts with their family and friends, and contagion risk. The incidence of new COVID-19 cases was also assessed. RESULTS: Overall, 283 LT and 57 RLD patients were included. We observed only eight COVID-19 cases over the three periods (n = 4 during T1, n = 0 during T2, and n = 4 during T3) in LT patients, with 37.5 % of patients hospitalized, no ICU transfers, and 100 % favorable outcomes. No case of COVID-19 was diagnosed in the RLD cohort. When comparing the three periods in the LT group, fewer patients limited their out-of-home activities during T2 (p < 0.0001). The frequency of these activities increased after the first lockdown, for the purchase of basic necessities (p < 0.0001), and professional activity continued (p = 0.008). We observed a significant increase in unscheduled medical consultations and in the prescription of anti-infective treatments during the end of the lockdown (p = 0.0002 and p = 0.005, respectively). Adherence to lockdown and to protective measures was high in both groups of patients. CONCLUSION: COVID-19 incidence remained low in both groups and there were significant lifestyle evolutions in LT patients and in those with RLD between first and second lockdown.

Profiles, diagnostic process, and patterns of care of patients with stage III non-small cell lung cancer: A French national study.

BACKGROUND: The management of stage III non-small-cell lung cancer (NSCLC) remains heterogeneous and complex, even after the approval of immune checkpoint inhibitors post-chemoradiotherapy (CRT). This observational study from France evaluated real-world practices in managing stage III NSCLC. METHODS: Between 2020 and 2022, we conducted a physician practice survey in 41 medical centers across France, and retrospectively analyzed aggregated information from 417 consecutive charts of patients with stage III NSCLC. We collected information on diagnostic and staging procedures, biomarker testing, surgical and non-surgical treatments, and follow-up. RESULTS: According to the physician survey, diagnostic workup of stage III NSCLC primarily relied on positron emission tomography/computed tomography and brain magnetic resonance imaging, performed for the majority of patients in 100 % and 78 % of centers, respectively. Of 417 patient charts, 414 were evaluable with 53 % of patients having stage IIIA disease, 37 % IIIB, and 10 % IIIC. The most common node involvement was N2 (59 %). Programmed death-ligand 1 testing was conducted for 98 % of patients. Invasive staging (mediastinoscopy or endobronchial ultrasound) was performed in 41 % of patients, of whom 83 % had N2 or N3 nodal involvement. Surgical resection was offered to 120 patients (29 %), with 85 % achieving R0 resection. In 292 charts of patients with unresectable stage III NSCLC, 190 patients (65 %) were offered CRT followed by consolidation immunotherapy. Within these patients, concurrent CRT was more frequently employed (52 %) than sequential CRT (13 %). CONCLUSIONS: Diagnostic procedures and treatment modalities in French medical centers generally align with clinical guidelines for stage III NSCLC, except for invasive staging that was less commonly performed than expected.

Healthcare-associated infections in patients with severe COVID-19 supported with extracorporeal membrane oxygenation: a nationwide cohort study.

BACKGROUND: Both critically ill patients with coronavirus disease 2019 (COVID-19) and patients receiving extracorporeal membrane oxygenation (ECMO) support exhibit a high incidence of healthcare-associated infections (HAI). However, data on incidence, microbiology, resistance patterns, and the impact of HAI on outcomes in patients receiving ECMO for severe COVID-19 remain limited. We aimed to report HAI incidence and microbiology in patients receiving ECMO for severe COVID-19 and to evaluate the impact of ECMO-associated infections (ECMO-AI) on in-hospital mortality. METHODS: For this study, we analyzed data from 701 patients included in the ECMOSARS registry which included COVID-19 patients supported by ECMO in France. RESULTS: Among 602 analyzed patients for whom HAI and hospital mortality data were available, 214 (36%) had ECMO-AI, resulting in an incidence rate of 27 ECMO-AI per 1000 ECMO days at risk. Of these, 154 patients had bloodstream infection (BSI) and 117 patients had ventilator-associated pneumonia (VAP). The responsible microorganisms were Enterobacteriaceae (34% for BSI and 48% for VAP), Enterococcus species (25% and 6%, respectively) and non-fermenting Gram-negative bacilli (13% and 20%, respectively). Fungal infections were also observed (10% for BSI and 3% for VAP), as were multidrug-resistant organisms (21% and 15%, respectively). Using a Cox multistate model, ECMO-AI were not found associated with hospital death (HR = 1.00 95% CI [0.79-1.26], p = 0.986). CONCLUSIONS: In a nationwide cohort of COVID-19 patients receiving ECMO support, we observed a high incidence of ECMO-AI. ECMO-AI were not found associated with hospital death. Trial registration number NCT04397588 (May 21, 2020).

Protective effect of height on long-term survival of resectable lung cancer: a new feature of the lung cancer paradox.

INTRODUCTION: Unlike most malignancies, higher body mass index (BMI) is associated with a reduced risk of lung cancer and improved prognosis after surgery. However, it remains controversial whether height, one of determinants of BMI, is associated with survival independently of BMI and other confounders. METHODS: We extracted data on all consecutive patients with resectable non-small cell lung cancer included in Epithor, the French Society of Thoracic and Cardiovascular Surgery database, over a 16-year period. Height was analysed as a continuous variable, and then categorised into four or three categories, according to sex-specific quantiles. Cox proportional hazards regression was used to estimate the association of height with survival, adjusted for age, tobacco consumption, forced expiratory volume in one second (FEV1), WHO performance status (WHO PS), American Society of Anesthesiologists (ASA) score, extent of resection, histological type, stage of disease and centre as a random effect, as well as BMI in a further analysis. RESULTS: The study included 61 379 patients. Higher height was significantly associated with better long-term survival after adjustment for other variables (adjusted HR 0.97 per 10 cm higher height, 95% CI 0.95 to 0.99); additional adjustment for BMI resulted in an identical HR. The prognostic impact of height was further confirmed by stratifying by age, ASA class, WHO PS and histological type. When stratifying by BMI class, there was no evidence of a differential association (p=0.93). When stratifying by stage of disease, the prognostic significance of height was maintained for all stages except IIIB-IV. CONCLUSIONS: Our study shows that height is an independent prognostic factor of resectable lung cancer.

Impact of surgical approach on 90-day mortality after lung resection for nonsmall cell lung cancer in high-risk operable patients.

Introduction: Non-small cell lung cancer (NSCLC) is often associated with compromised lung function. Real-world data on the impact of surgical approach in NSCLC patients with compromised lung function are still lacking. The objective of this study is to assess the potential impact of minimally invasive surgery (MIS) on 90-day post-operative mortality after anatomic lung resection in high-risk operable NSCLC patients. Methods: We conducted a retrospective multicentre study including all patients who underwent anatomic lung resection between January 2010 and October 2021 and registered in the Epithor database. High-risk patients were defined as those with a forced expiratory volume in 1 s (FEV1) or diffusing capacity of the lung for carbon monoxide (DLCO) value below 50%. Co-primary end-points were the impact of risk status on 90-day mortality and the impact of MIS on 90-day mortality in high-risk patients. Results: Of the 46 909 patients who met the inclusion criteria, 42 214 patients (90%) with both preoperative FEV1 and DLCO above 50% were included in the low-risk group, and 4695 patients (10%) with preoperative FEV1 and/or preoperative DLCO below 50% were included in the high-risk group. The 90-day mortality rate was significantly higher in the high-risk group compared to the low-risk group (280 (5.96%) versus 1301 (3.18%); p<0.0001). In high-risk patients, MIS was associated with lower 90-day mortality compared to open surgery in univariate analysis (OR=0.04 (0.02-0.05), p<0.001) and in multivariable analysis after propensity score matching (OR=0.46 (0.30-0.69), p<0.001). High-risk patients operated through MIS had a similar 90-day mortality rate compared to low-risk patients in general (3.10% versus 3.18% respectively). Conclusion: By examining the impact of surgical approaches on 90-day mortality using a nationwide database, we found that either preoperative FEV1 or DLCO below 50% is associated with higher 90-day mortality, which can be reduced by using minimally invasive surgical approaches. High-risk patients operated through MIS have a similar 90-day mortality rate as low-risk patients.