Thomas Gaisl

Background: Extracorporeal membrane oxygenation (ECMO) is a life-saving organ support for severe circulatory or respiratory failure, but it is frequently complicated by bleeding. Pulmonary haemorrhage and consecutive airway obstruction are major contributors to morbidity and mortality. Flexible bronchoscopy (FB) is indispensable for diagnosing and managing pulmonary bleeding; however, its safety and efficacy in ECMO patients remain insufficiently studied. This analysis evaluated the feasibility, safety, and short-term physiological effects of FB in critically ill adults supported with ECMO. Methods: In this single-centre retrospective study, all adult ECMO patients who underwent FB for endobronchial bleeding or obstructive clot formation between January 2020 and December 2024 at the University Hospital Zurich were included. The procedural indications, diagnostic findings, haemostatic interventions, anticoagulation management, and oxygenation parameters before and after FB were analysed. The bleeding severity was graded according to the level of intervention required for haemostasis. Results: Sixteen patients (median age: 51.5 years, 69% male) underwent 34 FB procedures while on ECMO (69% veno-arterial). Most procedures were therapeutic (71%) and performed for haemorrhage (35%) or airway obstruction (21%). Clot removal was attempted in 85% of bronchoscopies, achieving partial or complete clearance in most cases. The median PaO₂/FiO₂ ratio improved from 142.8 mmHg to 161.4 mmHg (post/pre ratio: 1.36); requiring a lower FiO2 (p = 0.049). Of the procedures performed for active bleeding, 24% were classified as severe, and bronchial blockers were required in 26%. Bleeding control failed in 12% of cases. The ICU mortality was 62.5%, with pulmonary haemorrhage directly causing death in 25%. Conclusions: FB is feasible in ECMO patients and provides a measurable short-term improvement in oxygenation. However, the high mortality underscores the severity of the underlying disease. Repeat FB likely reflects the disease burden rather than procedural inefficacy.

Background: Robotic-assisted bronchoscopy combined with integrated cone-beam computed tomography (RAB+CBCT) enables accurate sampling of peripheral pulmonary lesions (PPLs), but the acquisition of diagnostic proficiency and program-level efficiency remains incompletely characterized. Methods: We conducted a single-center cohort study of consecutive RAB+CBCT (Ion™ endoluminal system, Cios Spin) procedures performed by two experienced interventional pulmonologists. Strict lesion-level diagnostic yield was the primary outcome. Learning curve cumulative sum (LC-CUSUM) analysis determined operator-specific proficiency, followed by conventional CUSUM monitoring of post-proficiency performance. Secondary outcomes included procedure and intubation times, temporal changes in case complexity, and adverse events. Results: Overall, 427 procedures comprising 680 PPLs were analyzed. Median lesion long-axis diameter was 11 mm, 14.4% had a bronchus sign, and 36.5% of procedures involved multiple lesions. Strict lesion-level diagnostic yield was 85.4% (581/680). LC-CUSUM demonstrated proficiency after 48 and 86 PPLs, respectively; thereafter, both operators maintained acceptable performance without crossing the predefined CUSUM decision limit. Median procedure time decreased from 65 minutes during the first 10 procedures to 38 minutes during the last 10. The median intubation time was 70 minutes and declined significantly with increasing experience. Most indicators of lesion complexity remained stable, while short-axis diameter and bronchus-sign prevalence decreased modestly. Adverse-event frequency declined significantly over time. Conclusion: RAB+CBCT achieved high strict diagnostic yield, with heterogeneous operator-specific learning trajectories within a maturing multidisciplinary program. Diagnostic performance, procedural efficiency, and safety improved despite stable or modestly increasing case complexity. These findings support individualized, outcome-based proficiency assessment and longitudinal monitoring, rather than comparative operator ranking or reliance on fixed procedural-volume thresholds.

Background: Exhaled breath analysis offers notable advantages as a non-invasive method for obtaining biological information from lung cancer patients. However, since the 1980s, its successful translation into clinical practice has remained elusive. The primary challenges include the low concentrations of metabolites in exhaled breath, complexities in breath collection methodologies, difficulties in process standardisation, limited molecular coverage across different methods, and challenges in compound identification and in understanding their molecular origin. Comprehensive reviews by Amann et al. [2011], Hanna et al. [2018], Schmidt et al. [2023], and Vadala et al. [2023] provide holistic insights into the dynamic field of lung cancer breath research. This study aimed to evaluate the efficacy of real-time secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS) in differentiating lung cancer patients from matched controls based on breath metabolomic profiles. Methods: This prospective matched case-control study analysed 178 patients. The study included treatment-naive lung cancer patients and controls matched (1:1) on age, sex, and smoking status. SESI-HRMS was used for real-time breath analysis. Data processing was conducted through a validated multistep analytical framework. Statistical evaluation incorporated multivariate techniques and machine learning algorithms. High-resolution mass spectral features were assigned following the Schymanski [2014] classification, enabling the identification of distinct metabolic alterations. Results: SESI-HRMS identified 3,750 exhaled breath features. T-tests revealed 608 features with significant differences in intensity (P≤0.05) between cases and controls, of which 18 features remained significant after multiple testing correction (q≤0.05). Prediction model achieved reasonable performances. Cancer vs. controls was predicted with an accuracy of 0.75, sensitivity and specificity of 0.80 and 0.71, respectively. Functional enrichment analysis highlighted distinct metabolic pathways for different histological cancer types, including de novo fatty acid metabolism in adenocarcinoma and glucose metabolism in squamous cell carcinoma. Conclusions: Real-time SESI-HRMS breath analysis differentiated lung cancer patients with acceptable accuracy from matched controls and provides valuable metabolic insights in lung cancer. This non-invasive approach could complement existing methods like genome profiling and low-dose computed tomography, potentially enhancing early detection and personalised treatment strategies towards a multi-omics approach. Further research is warranted to validate these preliminary findings and to refine the identification of putative breath biomarkers.

Introduction: Lung cancer screening has increased the detection of peripheral pulmonary lesions (PPLs). Accurate diagnosis for therapy and prognosis is crucial but challenging. Our study compares the safety and efficacy of transbronchial cryobiopsy with two probe diameters and forceps biopsy. Methods: This single-centre, investigator-initiated, open-label, randomised trial included patients with PPLs who required flexible bronchoscopy with radial endobronchial ultrasound-guided biopsy for histopathological diagnosis. Patients received a forceps biopsy and were randomly assigned to a cryobiopsy with a 1.1 mm (freezing time 7-10 sec) or a 1.7mm cryoprobe (freezing time 4-6 sec), respectively. The primary outcome was the diagnostic yield; secondary outcomes included total biopsy size, the proportion of malignant tissue, artefact-free alveolar space percentage, molecular pathology of the specimen and safety. Results: Fifty-four patients (66.52±9.81 years; 48.1% male) with a median nodule size of 24mm [IQR 19 to 30] were included. The overall diagnostic yield was similar in the 1.1 mm and 1.7 mm groups (75.9% vs. 88.0%, p=0.261), and the specimens obtained with the two different cryoprobes were equal in size, quality, and information about molecular pathology. There was no difference in procedural-related bleeding between the groups (p=0.847). Compared to forceps biopsies, cryobiopsies had a superior overall diagnostic yield (75.9% vs. 48.1%, p=0.001) and were better suited for further molecular analysis (p=0.001). Conclusion: The 1.1 mm and 1.7 mm cryoprobes displayed comparable diagnostic yield, ability to provide molecular pathology information, and safety. Forceps biopsy was inferior to cryobiopsy in all aspects except safety.

Background: Limited data exist on the reliability, efficacy and safety of ultrasound-guided transbronchial cryobiopsy for suspicious mediastinal and hilar lesions. This study shares findings from implementing this method and compares the results with those of the standard endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Methods: Patients undergoing diagnostic bronchoscopy for mediastinal or hilar lesions in four Swiss centres were included. The study aims to assess the diagnostic yield and safety of EBUS-guided cryobiopsy compared with EBUS-TBNA. Tunnelling to the target lesion was performed using an electric needle knife (70.8%), a 19 G- (12.4%) or a 22 G needle (16.8%). Cryobiopsies were obtained with a freezing time of 4–7 s (18.2% with a 1.7 mm probe) or 6–10 s (81.8% with a 1.1 mm probe). Results: Altogether, 137 patients were enrolled with a median follow-up of 89 days. The overall diagnostic yield was 56.2% for EBUS-TBNA and 91.2% for cryobiopsies (p<0.001). Cryobiopsies increased the diagnostic yield for benign disorders (+28.5%), uncommon tumours (+5.9%) and other metastatic cancer (+0.6%), but not for lung cancer (+0%). For lung cancer (n=27), immunohistochemistry was obtainable in 40.7% of EBUS-TBNA (median of 3 probes [IQR 3 to 3]), significantly lower than cryobiopsy’s 88.9% yield (median of 4 probes [IQR 3 to 5]) (p<0.001). Adverse events were found in 23.4% of participants; 10.2% had mild to moderate bleeding, 0.7% had pneumonia, and 0.7% (one) of patients had pneumothorax following pneumomediastinum. No deaths or mediastinum infections were observed. Conclusion: Cryobiopsy of mediastinal and hilar lesions improves the diagnostic yield compared with EBUS-TBNA while maintaining a favourable safety profile.

This case report presents the diagnostic journey of a man in his mid-70s who experienced shortness of breath, cough, recurrent episodes of fever, weight loss, pruritic erythroderma, uveitis and macrocytic anaemia. The initial diagnosis of cryptogenic organising pneumonia was made based on antibiotic refractory infiltrates seen in the lung CT scan. The patient initially responded favourably to immunosuppression but experienced a recurrence of symptoms when the corticosteroid dose was tapered. Despite ongoing systemic inflammation and refractory symptoms, it took nearly a year to establish the diagnosis of VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic) syndrome. This case highlights the challenges in diagnosing and managing VEXAS syndrome due to its recent discovery and limited awareness in the medical community, as well as the need to consider this syndrome as a rare differential diagnosis of therapy-refractory pulmonary infiltrates.