Nuclear protein in testis (NUT) carcinoma is a rare, highly aggressive malignancy defined by NUTM1 rearrangement, most commonly involving BRD4. Nonspecific presentation and poorly differentiated histology lead to frequent misdiagnosis. Patients often present with large mediastinal masses, making swift diagnosis both important and challenging. A 29-year-old woman presented with two months of progressive dyspnea, cough, and fatigue accompanied by new-onset hemoptysis. CT demonstrated a large right hilar and mediastinal mass compressing the trachea, pulmonary artery, and superior vena cava (SVC). Rigid bronchoscopy was planned for biopsy and possible therapeutic debulking to control hemoptysis; the extracorporeal membrane oxygenation (ECMO) team was on standby, but the patient was not pre-cannulated. During induction of anesthesia, she developed profound refractory hypoxemia that persisted despite jet ventilation and airway optimization, attributed to loss of spontaneous respiratory effort and muscle tone with worsening dynamic central airway compression. Emergent femoral-femoral venovenous extracorporeal membrane oxygenation (VV-ECMO) was initiated, allowing the procedure to proceed safely. Bronchoscopy demonstrated severe right mainstem bronchial stenosis and complete obstruction of the right upper lobe by a friable endobronchial mass. Biopsies were nondiagnostic because of extensive necrosis and crush artifact, but the findings defined the extent of endobronchial disease and guided subsequent diagnostic planning. She was decannulated after two days of support, following clinical improvement sufficient to tolerate sitting upright. Supraclavicular lymph node sampling then established NUT carcinoma, confirmed by NUT immunohistochemistry (clone C52B1). Chemotherapy could not be initiated because of her critical clinical state, and she died two weeks after diagnosis. NUT carcinoma presents with nonspecific respiratory symptoms and is usually diagnosed at an advanced stage. Extensive necrosis reduces endobronchial biopsy yield, and alternative tissue sites should be pursued when initial sampling is nondiagnostic. Large mediastinal masses confer high risk of airway collapse and cardiovascular compromise during sedation; this case suggests that pre-emptive cannulation, rather than standby availability, warrants consideration when tracheal, pulmonary artery, and SVC compression coexist. VV-ECMO can stabilize patients with life-threatening respiratory failure and bridge them to definitive diagnostic evaluation. NUT carcinoma should be considered in young patients with rapidly progressive thoracic masses and poorly differentiated malignancy, with early confirmatory immunohistochemical or molecular testing.

Acute respiratory distress syndrome (ARDS) is a common and clinically significant complication in patients with acute brain injury (ABI), affecting up to one-third of critically ill individuals and contributing to increased mortality, prolonged mechanical ventilation, and worse neurological outcomes. The coexistence of ARDS and ABI creates a fundamental therapeutic dilemma: strategies that protect the lung may adversely affect cerebral physiology, whilst neuroprotective targets may compromise respiratory management. This narrative review examined the pathophysiological interactions between the injured lung and brain, highlighting the competing effects of key ventilatory variables. Lung-protective ventilation, including low tidal volume and higher positive end-expiratory pressure (PEEP), reduces ventilator-induced lung injury but may increase arterial carbon dioxide (PaCO2), resulting in intracranial hypertension and impaired cerebral perfusion. Conversely, strict control of PaCO2 and optimisation of cerebral perfusion may necessitate deviations from conventional ARDS strategies. Oxygenation targets further illustrate this tension, as both hypoxaemia and hyperoxaemia can exacerbate secondary brain injury. We synthesised current evidence on respiratory support, including non-invasive strategies, invasive mechanical ventilation, rescue therapies such as prone positioning and extracorporeal support, and pharmacological interventions, with emphasis on their differential effects on pulmonary and cerebral physiology. Attention was also given to the role of multimodal neuromonitoring, including intracranial pressure and brain tissue oxygenation, as tools to individualise ventilatory management and reconcile competing organ priorities. Overall, available data support a shift from protocolised approaches towards physiology-driven, patient-specific strategies that integrate lung mechanics, gas exchange and cerebral haemodynamics in patients with concomitant ARDS and ABI. Future studies should incorporate combined lung and brain endpoints to define strategies that simultaneously minimise ventilator-induced lung injury and secondary brain injury.

Early detection of acute lung injury (ALI) remains challenging, as conventional diagnostics rarely capture initial molecular changes. We therefore examined whether extracellular vesicles (EVs) in bronchoalveolar lavage fluid (BALF) can detect early regional injury and distinguish initial stress mechanisms in a porcine ALI model. Unilateral ALI was induced using Triton X-100, followed by six hours of mechanical ventilation with either fixed positive end-expiratory pressure (PEEP) at 5 cmH2O or transpulmonary-pressure (TPP)-guided PEEP. Spatially separated BALF sampling allowed direct comparison between injured and contralateral mechanically stressed lungs. EV concentration and size distribution were quantified by nano-flow cytometry, while vesicular identity was confirmed by transmission electron microscopy and tetraspanin dot blot analyses. Furthermore, EV metrics were related to corresponding histologic injury scores. Across both PEEP strategies, EV concentration was markedly higher in both directly injured and contralateral mechanically stressed lungs compared with sham controls, indicating alveolar stress beyond the primary injury site. Median EV size differed significantly by injury type and correlated inversely with histologic injury, particularly with alveolar neutrophil infiltration. BALF-derived EV concentration and size may therefore provide complementary, spatially resolved molecular readouts of early ALI.

Background/Objectives: Retained airway secretions are a common complication of mechanical ventilation and a major contributor to ventilator-associated pneumonia. Airway Pressure Release Ventilation following a Time-Controlled Adaptive Ventilation protocol (APRV-TCAV) has been anecdotally observed to improve secretion clearance, but the mechanism is not well established. Because TCAV sets the release time (TLow) from each patient's own expiratory flow decay, we hypothesized that the resulting expiratory-dominant flow profile would generate a net antegrade force on secretions. This bench study compared secretion movement between APRV-TCAV and conventional Volume-Control Continuous Mandatory Ventilation (VC-CMV), with and without an in-line oscillatory device. Methods: A critical care ventilator was connected to a 3 L test lung via a 7 mm endotracheal tube (ETT). Simulated mucus (1% guar gum) was instilled into the ETT, and secretion movement was measured under VC-CMV (positive end-expiratory pressure (PEEP) 5, 10, 15 cmH2O) and APRV-TCAV (PHigh 20, 25, 30 cmH2O; PLow 0 cmH2O). Each condition was repeated with an in-line oscillatory device. Results: All VC-CMV settings produced retrograde secretion movement toward the test lung; all APRV-TCAV settings produced antegrade movement. The largest antegrade movement was observed at the widest PHigh-to-PLow differential. Adding the oscillatory device raised peak expiratory flow above peak inspiratory flow in every condition, yet abolished antegrade movement under APRV-TCAV. Conclusions: In this bench study, APRV-TCAV reversed the direction of secretion movement within the ETT, with larger antegrade movement at wider PHigh-to-PLow differentials. This suggests a potential mechanism by which the ventilator flow profile itself may influence secretion movement. The directional effect depended on the intact release-phase waveform and was abolished by in-line oscillatory therapy despite preserved peak flow asymmetry.

Lung Ultrasound (LUS) has emerged in recent years as an extremely valuable diagnostic and monitoring tool, and as an increasingly standardized procedure in intensive care medicine. It provides rapid, radiation-free, bedside (POCUS: point-of-care ultrasound) diagnostics for thoracic diseases. Pathological Findings: LUS enables the detection of pathological lung findings such as pleural effusion, pneumothorax, consolidations including atelectasis and pneumonic infiltrates, as well as interstitial syndromes in the context of ARDS. In cases presenting with the key symptom of dyspnea, LUS helps to differentiate between cardiac, pulmonary, and combined causes (BLUE protocol). Scoring systems - e.g., the Lung Ultrasound Score (LUSS) - quantify the severity and course of lung changes in pneumonia or ARDS and support therapeutic decision-making. LUS can thus be used in critically ill patients to assess the effectiveness of ventilation strategies and to monitor the progression of respiratory failure. Interventions and Weaning: LUS is also an important tool in thoracic interventions such as punctures or drain placements, as it increases safety and precision. In the weaning process of invasively ventilated patients, ultrasound provides valuable information, for example on lung aeration and the risk of weaning failure. Sonographic access to the lung is limited to intercostal spaces; however, approximately 70% of the pleural surface is accessible. Central lung processes, particularly in ventilated lungs without consolidations, cannot be visualized sonographically.

Objective This study aimed to identify monocyte/macrophage-related hub genes in ventilator-induced lung injury (VILI) by integrating transcriptomic analysis, immune infiltration analysis, weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network analysis, and machine learning approaches, followed by experimental validation using a VILI animal model. Methods Seven mouse lung transcriptomic datasets related to VILI were obtained from the Gene Expression Omnibus (GEO) database and integrated after normalization and batch effect correction. Differential expression analysis was performed to identify VILI-associated genes. Immune infiltration analysis and WGCNA were applied to characterize changes in the pulmonary immune microenvironment and identify modules correlated with monocyte/macrophage infiltration. Key module genes were intersected with VILI-related differentially expressed genes (DEGs) and subsequently subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and PPI analyses. Based on monocyte/macrophage infiltration levels, samples were stratified, and candidate genes were screened using least absolute shrinkage and selection operator (LASSO) regression, support vector machine-recursive feature elimination (SVM-RFE), and the random forest algorithm. Receiver operating characteristic (ROC) curve analysis was then performed to evaluate the discriminatory performance of the selected genes. Finally, experimental validation was conducted using histological analysis, bronchoalveolar lavage fluid cytokine assays, quantitative real-time polymerase chain reaction (qPCR), and immunofluorescence staining. Results Lung tissues from VILI model mice showed marked remodeling of the immune microenvironment, characterized by increased proportions of monocytes/macrophages and neutrophils, along with reduced CD4 T cell- and innate lymphoid cell-related populations. The MEblack module was positively correlated with monocyte/macrophage infiltration (r = 0.64) and was selected as the key module. Intersecting MEblack genes with VILI-related differentially expressed genes identified 99 candidate genes mainly enriched in chemotaxis, inflammatory response regulation, leukocyte migration, and IL-17, TNF, and NF-κB signaling pathways. Stratification by monocyte/macrophage abundance further identified 82 common differentially expressed genes with similar enrichment patterns. Three machine-learning algorithms jointly prioritized Ccr1, Mmp9, and Il36g as core feature genes, all of which were upregulated in VILI. ROC analysis showed the strongest discriminatory performance for Ccr1 (area under the curve (AUC) = 0.987), followed by Il36g (AUC = 0.891) and Mmp9 (AUC = 0.883). Experimental validation confirmed inflammatory infiltration, structural lung injury, elevated IL-1β, IL-6, and TNF-α levels, increased expression of the three hub genes, and enhanced CCR1-positive signals in alveolar septal and perivascular regions. Conclusions VILI is associated with monocyte/macrophage infiltration and activation of inflammatory chemotaxis-related pathways. Ccr1, Mmp9, and Il36g may serve as monocyte/macrophage-related inflammatory feature genes, with Ccr1 showing particular promise as a candidate biomarker of pulmonary inflammatory activation in VILI.

Pulmonary sequestration (PS) is a rare congenital malformation characterized by a mass of non-functioning, dysplastic lung tissue that lacks normal tracheobronchial communication and receives its blood supply from an aberrant systemic artery. Although advances in prenatal ultrasonography have significantly improved early detection rates, a subset of cases remains undiagnosed until postnatal clinical symptoms emerge. Extralobar sequestration (ELS) in particular typically presents during the neonatal period, frequently manifesting as acute respiratory distress. We present the case of a term male neonate who developed progressive respiratory failure within the first hours of life, despite a completely unremarkable prenatal ultrasound history. Initially managed with non-invasive positive airway pressure, his clinical condition rapidly deteriorated, necessitating endotracheal intubation and invasive mechanical ventilation. Concurrently, the patient was diagnosed with severe congenital pneumonia caused by extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae. While early chest radiographs showed bilateral diffuse opacities without definitive structural anomalies, follow-up imaging on the fifth day of life revealed a large, persistent consolidation in the right lower lobe. Subsequent contrast-enhanced computed tomography angiography (CTA) confirmed the presence of an extralobar pulmonary sequestration measuring approximately 37.5 × 20 × 53 mm. Notably, the CTA identified a rare anatomical variant: the aberrant feeding artery originated directly from the right renal artery, rather than the more typical thoracic or abdominal aorta. Following targeted antibiotic therapy and stabilization of his respiratory status, the patient underwent successful surgical resection of the sequestered lobe on the tenth day of life. Histopathological examination definitively confirmed the ELS diagnosis. The neonate was successfully extubated on the day of surgery, demonstrated an excellent postoperative recovery without requiring supplemental oxygen, and was discharged home on day 22. This case emphasizes the critical need to include congenital lung malformations in the differential diagnosis of unexplained neonatal respiratory failure, even in the context of normal prenatal imaging. Furthermore, the presence of an atypical feeding artery originating from the renal artery underscores the absolute necessity of detailed preoperative vascular mapping with CTA to optimize surgical planning, minimize intraoperative risks, and ensure a favorable clinical outcome.