Background: Mounting evidence suggests that medical management may differ significantly between female and male patients. Despite studies showing increased sensitivity to pain, female patients receive less opioid analgesia compared to male patients after surgery. It is uncertain whether perioperative multimodal analgesia differs between sexes in thoracic surgery. Methods: A retrospective cohort study from January to July 2023 comparing multimodal analgesia and perceived pain in the early postoperative period between female and male patients after video-assisted thoracic surgery (VATS). The primary endpoint was the opioid demand in the post-anaesthesia care unit (PACU). Secondary outcomes included pain scores, regional anaesthesia and pain therapy by female, male or mixed teams. Results: Overall, 46.0% (n = 92) of the 200 included patients were female and 54% (n = 108) were male. Following VATS, the median piritramide demand was 9.0 [5.3 to 14.9] mg in female vs. 7.7 [4.5 to 12.9] mg in male patients (p = 0.35). Pain scores and regional anaesthesia were comparable between groups. In the early postoperative period, more opioids were administered overall and to female patients by all female anaesthesia teams, compared to mixed or all-male teams. Conclusions: The weight-adjusted dose of postoperative opioids did not differ between groups; neither did postoperative pain scores or the application of nerve blocks. The increased opioid demand in female patients was met by all female teams but not by all-male or mixed teams.

BACKGROUND:Primary graft dysfunction grading is an important prognostic parameter following lung transplantation. Because the current ISHLT consensus classification does not differentiate between mechanically ventilated and extubated patients, we examined whether mechanical ventilation status influences the prognostic value of PGD grades for short- and long-term outcomes. METHODS:All primary bilateral lung transplants performed at the Medical University of Vienna and Vanderbilt University Medical Center (January 2017 - December 2024) were retrospectively analyzed. PGD was adjudicated per the 2016 ISHLT Consensus Statement. At each postoperative time point (T24, T48, T72), patients were stratified by PGD grade and ventilation status. ICU-free and hospital-free days were compared using Bonferroni-corrected Wilcoxon rank-sum tests. Long-term survival was assessed using Kaplan-Meier analysis and Cox models adjusted for PGD grade, center, donor and recipient age, sex, diagnosis, and ECMO bridge-to-transplant. RESULTS:Among 1022 patients, 311 (30.4%) were extubated by T24, 560 (54.8%) by T48, and 651 (63.7%) by T72. Extubated patients had more ICU-free and hospital-free days across most PGD grades and time points. Kaplan-Meier analysis demonstrated significantly better survival for extubated patients among PGD 0/1 at all time points and PGD 2/3 at T24 and T48. After multivariable adjustment, mechanical ventilation was independently associated with worse survival among PGD 0/1 at T72 (HR 1.56, 95% CI: 1.12-2.16) and PGD 2/3 at T48 (HR 2.68, 95% CI: 1.20-5.98). The association within PGD2/3 at T72 did not reach statistical significance. CONCLUSIONS:Mechanical ventilation status carries prognostic information not captured by the current PGD grade. Within PGD0/1 at 72 h, the largest subgroup in the cohort, mechanical ventilation was independently associated with worse long-term survival, a finding that replicated at both centers. Future PGD classification revisions should include ventilatory status to improve prognostic accuracy.

BACKGROUND:The lack of physiologic clearance mechanisms during ex vivo lung perfusion (EVLP) may lead to electrolyte imbalances, accumulation of toxic metabolites and disturbances in starling forces. The integration of dialysis may help to maintain perfusate physiology. The FILONEX trial investigates the feasibility and safety of this strategy. METHODS:This single-center prospective randomized controlled study included 30 marginal donor lungs randomized 1:1 at procurement. Normothermic acellular EVLP was performed for six hours. After one hour, hemodiafiltration (HDF) was added to the EVLP circuit in the treatment group, whereas the control group received EVLP without any adjunct therapy. Primary endpoints were suitability for transplantation after EVLP, and primary graft dysfunction (PGD) grade 3 at 72 h after transplantation. RESULTS:Donor and recipient characteristics were similar between the groups. Electrolyte levels, lactate and pH remained within physiological ranges only in the treatment group. Acceptance rate was 47% (n=7) in the control and 80% (n=12) in the treatment group. PGD grade 3 at ICU admission was 57% (n=4) in the control and 25% (n=3) in the treatment group (p=0.093). There were no cases of PGD grade 3 at 72 h in either group. In 3 (43%) control patients, VA-ECMO was prolonged postoperatively compared to 1 (8%) patient in the treatment group (p=0.075). Length of mechanical ventilation, ICU stay, hospital stay and short-term mortality were comparable among the groups. CONCLUSION:This prospective randomized trial demonstrates that integrating HDF into the EVLP circuit is feasible and safe during six hours of perfusion, without adverse effects on EVLP performance or short-term outcomes after lung transplantation.

BACKGROUND:Patients with suspicious pulmonary lesions are traditionally rejected or delisted for lung transplantation (LTx). Data on the overall prevalence of suspicious lung lesions in candidates for LTx, their characteristics, and the proportion of malignancy among these lesions are lacking. METHODS:We performed a retrospective analysis of all patients with suspicious lung nodules who underwent LTx between January 2012 and October 2022. We compared characteristics of lesions, assessed definitive histology reports, analyzed postoperative outcomes, and calculated overall survival at 1-, 3-, and 5-years. RESULTS:Out of 1070 transplanted patients, 79 (7.4%) had suspicious lung lesions prior to LTx. In this group, COPD was the most frequent indication for LTx (83.5% of patients). Pathology reports confirmed lung cancer in explanted native lungs in only 12 of the 79 patients (15.1%). The most common lung cancer entity was adenocarcinoma in 8 patients (66.7%). Ten of the 12 (83.3%) patients were in stage I, II and 2 (16.6%) patients were in stage-IIIA disease based on final histological work-up after LTx. Overall survival did not differ between 'malignant nodules' subgroup, 'non-malignant nodules' subgroup and their respective matched controls at 1 year (87.5% vs 89.7% vs 88.2%), 3 years (87.5% vs 78.6% vs 77.5%) or 5 years (87.5% vs 70.1% vs 68.6%) (cox proportional-hazards model, p=0.541). CONCLUSIONS:Patients with unverified suspicious lung lesions should not be excluded from LTx, as only a small proportion of these nodules are malignant. Long-term survival is unaffected even in cases the explanted lung harbors an early-stage lung cancer.

OBJECTIVES In patients with interstitial lung disease (ILD), the diaphragm typically rises as the lungs chronically shrink. However, the grade of restriction differs in each patient. It is currently unknown, how disparities between actual and predicted recipient total lung capacity (TLC), impact changes in lung function parameters and long-term outcomes following lung transplantation (LTx). METHODS This retrospective study included 170 LTx for the patients with ILD performed in a European high-volume LTx center between 09/2011 and 12/2022. The preoperative median ratio of recipient actual to predicted (a/p) TLC was 0.55. Patients were stratified into two groups: low a/p TLC ratio group, corresponding to a more restricted chest cavity (<0.55: n = 85), and high a/p TLC ratio group, corresponding to a more preserved chest cavity (>= 0.55: n = 85). Perioperative and long-term outcomes, including lung function and overall survival, were analysed. RESULTS Between the two groups, tracheostomy and reintubation rates, length of mechanical ventilation, ICU-stay and hospital-stay were not significantly different. Although lung function measurements obtained early after LTx were better in the high a/p TLC ratio group, no significant differences were observed in the long term. Five-year overall survival was not significantly different between the two groups. CONCLUSIONS Although LTx for ILD patients with a restricted chest is considered technically more challenging, the perioperative course is similar to ILD patients with a preserved chest. In addition, no significant differences were observed between both groups in long-term lung function and overall survival, suggesting an improvement in chest wall compliance.

A rare but important complication after lung transplantation (LTx) is postoperative phrenic nerve dysfunction (PND). Diaphragmatic plication (DP) is a well-established treatment option for PND, however, the long-term effect of PND and DP on lung function parameters and survival after LTx are currently unknown. We retrospectively reviewed 1400 LTx recipients transplanted at Medical University of Vienna between 01/2003 and 12/2022. Fluoroscopy and/or phrenic nerve conduction studies confirmed PND when chest radiographs after extubation showed a unilateral heightened diaphragm. We identified 25 patients with post-operative PND, of whom 12 underwent DP. The remaining 1,375 patients served as a control group. Median ICU-stay and hospital-stay were significantly longer in the PND groups (DP: 20 and 57 days; non-DP: 27 and 43 days; control group: 7 and 25 days; P = 0.001/P < 0.001). PND led to consistently lower %TLC in lung function tests performed within the first three years after LTx. DP was associated with lower %FEV1.0 early after LTx but it aligned to %FEV1.0 of the other groups during follow-up. Although PND significantly affected postoperative recovery after LTx, it did not impair long-term survival outcomes.

Objective: Although retransplantation is the main therapeutic option for end-stage chronic lung allograft dysfunction, several transplant centers consider the "restric- tive allograft syndrome" phenotype a contraindication. This selection policy is based on a limited body of literature. The aim of this study was to investigate the association of chronic lung allograft dysfunction phenotypes according to new chronic lung allograft dysfunction definitions with outcomes after retransplantation. Methods: This study was a retrospective single-center analysis including patients undergoing lung retransplantation due to chronic lung allograft dysfunction between 2000 and 2021. Results: Seventy patients were included in the analysis, 73% had bronchiolitis obliterans syndrome, 20% had a mixed phenotype, and 7% had restrictive allograft syndrome. The length of surgery was comparable between the groups. No difference was observed in terms of intraoperative use of packed red blood cells (P = .407), fresh-frozen plasma (P = .173), platelets (P = .300), prothrombin complex concentrates (P = .381), and fibrinogen (P = .808). Patients with non- bronchiolitis obliterans syndrome were more often graded with primary graft dysfunction 3 at arrival to the intensive care unit, and this trend remained at 72 hours after transplantation. After 72 hours, 60% of the cohort was extubated or had primary graft dysfunction grade 0. Early postoperative outcome was comparable between the groups. Survival between the groups did not differ with overall survivals at 1, 5, and 10 years of 72%, 53%, and 51% for bronchiolitis obliterans syndrome and 71%, 56%, and 42% for non-bronchiolitis obliterans syndrome, respectively (P = .841). Conclusions: This analysis showed that retransplantation remains a challenging procedure. However, careful patient selection allows excellent outcomes irrespective of chronic lung allograft dysfunction phenotypes. (JTCVS Open 2025;23:335-48)

Lung transplantation is often the sole and final therapeutic option for patients with end-stage lung disease. In recent years, clinical outcomes have steadily improved, driven in part by advancements in extracorporeal mechanical support. These techniques have become an integral component of routine clinical practice, particularly in lung transplantation centres. Extracorporeal lung support systems range from relatively simple pumpless devices to complex cannulation techniques and device configurations. In particular, extracorporeal membrane oxygenation (ECMO) encompasses various configurations widely utilised in thoracic surgery, especially in lung transplantation. A distinction can be made between preoperative ECMO, referred to as bridge-to-transplant, and intraoperative ECMO support, which is employed during the transplantation procedure. In recent years, intraoperative ECMO has largely replaced the traditional heart-lung machine. Additionally, ECMO plays a critical role in the immediate postoperative period, both in preventing and managing primary graft dysfunction. Beyond lung transplantation, extracorporeal life support systems are also applied in complex thoracic surgical resections and procedures involving the central airways. In the future, technical advancements and improvements in treatment protocols are expected to further enhance the role of extracorporeal mechanical support in the management of thoracic surgical patients.

There is accumulating evidence that chronic mental stress leads to immune checkpoint inhibitor (ICI) therapy resistance and negatively impacts outcome in cancer patients, but molecular mechanisms remain elusive. In two retrospective lung cancer cohorts we assessed amygdala status as primary marker for chronic stress, tumor parameters and bone marrow activation by whole body [18F]FDG-PET at initial diagnosis. In C1 194 lung cancer patients receiving traditional therapies were followed for 85.5 months and in C2 60 lung cancer patients receiving ICI-therapy in the first line were assessed for therapy response using the Junker scoring system. Subjects were dichotomized into chronic and low stress, based on amygdalar activity. Tumor volumes were delineated semi-automatically and TLG served as marker of tumor metabolic activity and FDG uptake in the bone marrow was normalized to blood pool activity. For molecular analysis twenty bio-banked tissue samples were used for full genomic sequencing, spatial analysis of tumor tissue was performed using multiplexed immunohistochemistry and spatial transcriptomics (10xgenomics). Univariate regression analysis identified the primary stress marker (P < 0·001*) predict a death event within 1 year. Moreover, chronic stress correlated significantly with bone marrow (r = 0·24, P = 0·001*) and CRP (r = 0·21, P = 0·006*), but not with TLG (r = 0·1). Multi-omics analysis of 20 therapy naïve tumor samples identifies chronic stress attenuates in the tumor tissue IFN-γ signaling (P = 0·01, NES = -1·58) and the tumor microenvironment harbours a reduced number of cytotoxic T cells, which are however more frequently in the vicinity of PD-L1 expressing cells (P = 0·009*). A mediation analysis confirmed the direct effect (4.1, P = 0.008*) between the primary stress measure and one-year survival, and also a statistically significant indirect effect (0.5, P < 0.05*), showing that the relation was serially mediated via (i) inflammation and (ii) TLG. In C2 68% of patients with ICI therapy showed a complete or almost complete pathological response (Junker 2b or Junker 3), while 32% had a response of Junker 2a or worse. While among the non-responding patients 60% displayed the stress marker high AmygAc, only 13% of the responders were chronically stressed. We show that therapy naïve lung cancer patients can be stratified by [18F]FDG amygdalar activity into chronically stressed individuals with lower life expectancy (C1) and ICI-therapy resistance (C2). The TME in these patients lacks IFN-γ signaling and activated T cells in the tumor, which we propose as molecular mechanism mediating the stress induced bad outcome. Barbara Katharina Geist, Chrysoula Vraka, Thomas Selim Nakuz, Karolina Trachtova, Song Xue, Chengcheng Shi, Kilian Kluge, Oana Kulterer, Josef Yu, Laurin Herbsthofer, Alessandro Liebich, Martina Tomberger, Thomas Schweiger, Helmut Prosch, Felicitas Oberndorfer, Constantin Lapa, Xinli Xie, Hong Zong, Lukas Kenner, Stefan Gruenert, Marcus Hacker. Chronic emotional distress in lung cancer is associated with attenuated IFN-gamma-signaling and dysfunctional T cells, diminished response to immune checkpoint blockade and adverse outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB374.

Background Airway surgery remains a rarely performed procedure and reports on complication rates are scarce in the literature. Given several recent technical advances in airway surgery, we aimed to assess the rates of procedure-associated complications in a contemporary, multi-institutional cohort of patients. Methods Airway resections performed between January 2013 and December 2023 in 3 European institutions with a dedicated airway program were included in this retrospective analysis. Results A total of 640 patients were included in the analysis. This included 313 tracheal, 309 cricotracheal, and 18 laryngotracheal reconstructions with rib cartilage interpositions. The median length of resection was 25 mm (range, 8-70 mm). The median hospital length of stay was 6 days (interquartile range, [IQR], 5-9 days). In-hospital mortality was recorded in 2 patients (0.3%). The most prevalent early complication was glottic swelling (5%), followed by surgical site infection (4%). Anastomosis dehiscence was a rare event, with 12 partial dehiscences (2%). Most patients (93%) experienced normal healing of their anastomosis. Granuloma formation was noted in 3.3% of patients, restenosis in 3.1%, and malacia in 0.2%. With a median follow-up of 2 years and 5 months (IQR, 4-47 months), only 5 patients (0.7%) required a stent, 2 (0.3%) required a T-tube, and 9 (1.4%) underwent a permanent tracheostomy. Conclusions This large, contemporary, international cohort of airway cases demonstrates that complications following airway resection are significantly lower than previously reported. This finding is crucial for informed and shared decision making with patients suffering from operable airway conditions.

Idiopathic subglottic stenosis (ISGS) is a rare fibrotic disease of the upper trachea with an unknown pathomechanism. It typically affects adult Caucasian female patients, leading to severe airway constrictions caused by progressive scar formation and inflammation with clinical symptoms of dyspnoea, stridor and potential changes to the voice. Endoscopic treatment frequently leads to recurrence, whereas surgical resection and reconstruction provides excellent long-term functional outcome. This study aimed to identify so far unrecognized pathologic aspects of ISGS using single cell RNA sequencing. Our scRNAseq analysis uncovered the cellular composition of the subglottic scar tissue, including the presence of a pathologic, profibrotic fibroblast subtype and the presence of Schwann cells in a profibrotic state. In addition, a pathology-associated increase of plasma cells was identified. Using extended bioinformatics analyses, we decoded pathology-associated changes of factors of the extracellular matrix. Our data identified ongoing fibrotic processes in ISGS and provide novel insights on the contribution of fibroblasts, Schwann cells and plasma cells to the pathogenesis of ISGS. This knowledge could impact the development of novel approaches for diagnosis and therapy of ISGS.

OBJECTIVES:Compared to lung resections, airway procedures are relatively rare in thoracic surgery. Despite this, a growing number of dedicated airway centres have formed throughout Europe. These centres are characterized by a close interdisciplinary collaboration and they often act as supra-regional referring centres. To date, most evidence of airway surgery comes from retrospective, single-centre analysis as there is a lack of large-scale, multi-institutional databases. METHODS:In 2018, an initiative was formed, which aimed to create an airway database within the framework of the ESTS database (ESTS-AIR). Five dedicated airway centres were asked to test the database in a pilot phase. A 1st descriptive analysis of ESTS-AIR was performed. RESULTS:A total of 415 cases were included in the analysis. For adults, the most common indication for airway surgery was post-tracheostomy stenosis and idiopathic subglottic stenosis; in children, most resections/reconstructions had to be performed for post-intubation stenosis. Malignant indications required significantly longer resections [36.0 (21.4-50.6) mm] when compared to benign indications [26.6 (9.4-43.8) mm]. Length of hospital stay was 11.0 (4.1-17.3) days (adults) and 13.4 (7.6-19.6) days (children). Overall, the rates of complications were low with wound infections being reported as the most common morbidity. CONCLUSIONS:This evaluation of the 1st cases in the ESTS-AIR database allowed a large-scale analysis of the practice of airway surgery in dedicated European airway centres. It provides proof for the functionality of ESTS-AIR and sets the basis for rolling out the AIR subsection to all centres participating in the ESTS database.

Background In older patients, a limited physical reserve is considered a contraindication for lung transplantation (LTx). Herein, we aimed to establish a computed tomography (CT)-based quantification of physical reserve in older patients scheduled for transplantation. Methods This retrospective study included patients older than 60 years who received LTx. Semiautomatic measurements of the mediastinal fat area and the dorsal muscle group area in pretransplantation CT scans were performed, and normalized data were correlated with clinical parameters. Results Patients ( n = 108) were assigned into three groups (Muscle( high) fat( low) [ n = 25], Muscle( low) fat( high) [ n = 24], and other combinations [ n = 59]). The Muscle( low) fat (high) group had a significantly increased risk of wound infections ( p = 0.002) and tracheostomy ( p = 0.001) compared with Muscle( high) fat( low) patients. The median length of intensive care unit stay (25 vs. 3.5 days; p = 0.002) and the median length of hospital stay (44 vs. 22.5 days; p = 0.013) post-LTx were significantly prolonged in the Muscle( low) fat( high) group. Significantly more patients in this group had a prolonged ventilation time (11 vs. 0; p < 0.001). Conclusion Body composition parameters determined in pretransplant chest CT scans in older LTx candidates might aid in identifying high-risk patients with a worse perioperative outcome after LTx.

This case demonstrates that, under special precautions, general anesthesia using an LMA SupremeTM with extended monitoring of the mother and the fetus can safely be provided for pregnant patients in need of urgent CTR. Close communication and cooperation between the involved disciplines, however, is of paramount importance.

OBJECTIVES: Dual-lumen cannulas for veno-venous (VV) extracorporeal membrane oxygenation (ECMO) support are typically inserted in the right internal jugular vein (RIJV); however, some scenarios can make this venous route inaccessible. This multicentre case series aims to evaluate if single-site cannulation using an alternative venous access is safe and feasible in patients with an inaccessible RIJV. METHODS: We performed a multi-institutional retrospective analysis including high-volume ECMO centres with substantial experience in dual-lumen cannulation (DLC) (defined as >10 DLC per year). Three centres [Freiburg (Germany), Toronto (Canada) and Vienna (Austria)] agreed to share their data, including baseline characteristics, technical ECMO and cannulation data as well as complications related to ECMO cannulation and outcome. RESULTS: A total of 20 patients received alternative DLC for respiratory failure. Cannula insertion sites included the left internal jugular vein (n = 5), the right (n = 7) or left (n = 3) subclavian vein and the right (n = 4) or left (n = 1) femoral vein. The median cannula size was 26 (19-28) French. The median initial target ECMO flow was 2.9 (1.8-3.1) l/min and corresponded with used cannula size and estimated cardiac output. No procedural complications were reported during cannulation and median ECMO runtime was 15 (9-22) days. Ten patients were successfully bridged to lung transplantation (n = 5) or lung recovery (n = 5). Ten patients died during or after ECMO support. CONCLUSIONS: Alternative venous access sites for single-site dual-lumen catheters are a safe and feasible option to provide veno-venous ECMO support to patients with inaccessible RIJV.

OBJECTIVES:Treatment options for benign subglottic stenosis include endoscopic techniques or open surgery. Although endoscopic treatment is less invasive, a considerable proportion of patients develop recurrent stenosis. Endoscopic pretreatments do not exclude patients from a later surgical repair; however, the impact of previous endoscopic treatment attempts on functional outcome after open surgery is unknown. METHODS:All patients, who received a cricotracheal resection (CTR) between January 2017 and June 2023 at the Department of Thoracic Surgery, Medical University of Vienna, were included in this retrospective study. Patient characteristics, surgical variables and postoperative outcome including a detailed functional assessment were analysed. RESULTS:A total of 65 patients received a CTR during the study period, of which 40 were treatment naïve and 25 had a median of 2 (range 1-9) endoscopic pretreatments. Less-invasive voice-sparing CTR or standard CTR were more often possible in treatment-naïve patients. In contrary, pretreated patients regularly required extended procedures (P = 0.049). Three or more endoscopic treatments resulted in a significantly lower mean fundamental frequency (F0) after open repair (P = 0.048). In addition, a trend towards smaller mean sound pressure levels, a higher voice handicap index, higher impairments in RBH scores (roughness, breathing and hoarseness) and a higher dysphagia severity index was found in pretreated patients. The respiratory outcome after surgery was comparable between both groups. CONCLUSIONS:Multiple endoscopic pretreatments lead to worse voice quality after CTR. The impact of prior endoscopic treatment before surgical repair should be considered when discussing treatment options with patients suffering from subglottic stenosis.

The diagnosis and treatment of patients with tracheal tumors is challenging due to the low incidence of these tumors. A precise diagnostic work-up and experience is necessary to distinguish between patients amenable to surgery and nonsurgical patients. An individualized treatment concept should be established for each patient in a multidisciplinary team and ranges from interventional removal of benign lesions to multimodal strategies in patients with extended malignant tumors. Early diagnosis despite unspecific symptoms and complete resection are crucially important to achieve long-term survival.