Glucose and oxygen availability are fundamental drivers of tumor progression, deeply influencing cancer cell proliferation, metabolism, and spatial organization. In this study, we present a simplified microfluidic-based 3D model of tumorigenesis that allows for controlled and dynamic analysis of key tumor parameters under metabolic stress. Using this platform, lung adenocarcinoma (A549) spheroids embedded in a collagen-based extracellular matrix were monitored over time to assess growth kinetics, hypoxic response via HIF-1α expression, and structural organization. A multifactorial experimental design combining variations in glucose, glutamine, and oxygen availability revealed distinct and specific effects of each nutrient. Glutamine deprivation led to widespread cell death, while glucose limitation strongly arrests cell proliferation. Finally, oxygen restriction disrupted spheroid architecture, resulting in loss of the proliferative outer capsule and the formation of internal cavities. Our approach provides a flexible system to study how microenvironmental cues shape tumor behavior, offering insights into metabolic vulnerabilities and the morphofunctional consequences of nutrient stress in cancer.

BackgroundWhen transplant clinicians encounter ethical challenges and are constrained by their institution from acting in a manner within their professional ethical obligations, they may experience moral distress. Moral distress has been associated with negative effects such as burnout and turnover. Conversely, high grit has been positively correlated with job satisfaction, job performance, and organizational commitment.Research questionsWhat is the level of grit and moral distress among transplant clinicians? What correlations between demographics, grit, moral distress, and intent to leave exist among transplant clinicians?Research designThis cross-sectional study was conducted from October 2024 through March 2025. Three instruments, an investigator-developed demographic survey, the 12-Item Grit Scale, and the Measure of Moral Distress for Healthcare Professionals, were used to capture transplant clinician's grit and level of moral distress. Data were analyzed using descriptive statistics, Pearson correlation, and generalized structural equation modeling.Participants and research contextThe target population for this study consisted of organ transplant clinicians (e.g., surgeons, physicians, coordinators, advanced practice providers, nurses, and allied health team members) in the United States.Ethical considerationsEthics review and approval was obtained prior to subject recruitment.ResultsAmong 101 transplant clinicians, higher moral distress was observed in those with advanced education, frequent ethical challenges, and specific transplant roles (e.g., advanced practice providers, physicians, multi-organ), while grit remained consistent across demographic and clinical factors. Generalized structural equation modeling suggests a potential mediating role between clinician characteristics (education), workforce factors (frequent ethical issues and specific transplant roles), and turnover intentions.ConclusionTransplant clinicians who experience moral distress frequently and at high intensity may express an intent to leave their role regardless of their level of grit. Healthcare organizations must create targeted interventions and resources to mitigate moral distress and support transplant clinicians who experience moral distressing events.

Coccidioidomycosis is an endemic fungal infection of the southwestern United States that may rarely produce mass-like pulmonary abnormalities mimicking malignancy. We describe a 70-year-old Hispanic woman with poorly controlled type 2 diabetes mellitus (HbA1c >14%) who presented after three days of generalized weakness, nonproductive cough, abdominal pain, nausea, vomiting, and progressive difficulty ambulating. CT demonstrated a 7.3 × 5.4 cm wedge-shaped necrotic right middle lobe mass with multiple bilateral pulmonary nodules. CT-guided biopsy of the mass demonstrated granulomatous inflammation with fungal elements, while subsequent serologic testing and bronchoalveolar lavage PCR supported pulmonary coccidioidomycosis. Her hospitalization was complicated by acute respiratory distress syndrome requiring invasive mechanical ventilation, prone positioning, and neuromuscular blockade; non-liposomal amphotericin B-associated acute tubular necrosis requiring hemodialysis; ventilator-associated Klebsiella pneumoniae pneumonia; and persistent encephalopathy with multifocal MRI abnormalities highly suggestive of central nervous system dissemination despite nondiagnostic cerebrospinal fluid studies. This case highlights how pulmonary coccidioidomycosis can mimic malignancy. It illustrates the multifactorial deterioration that may occur in susceptible hosts, emphasizing early tissue diagnosis, careful interpretation of suspected dissemination, and individualized antifungal and critical care management.

Introduction Timely liberation from mechanical ventilation is a central goal of critical care. This study aimed to compare two point-of-care ultrasound indices, the diaphragmatic rapid shallow breathing index (D-RSBI) and the diaphragmatic thickness fraction (DTF), in predicting successful weaning among mechanically ventilated adults. Methods In this prospective, single-center diagnostic-accuracy study, 44 adults who were mechanically ventilated for more than 48 hours but fewer than seven days and who met the readiness criteria for a spontaneous breathing trial (SBT) underwent diaphragm and lung ultrasound before the trial. Weaning outcomes were categorized using the Weaning according to a New Definition (WIND) framework; successful weaning (simple or difficult categories, n = 36) was the reference standard, whereas prolonged weaning (n = 8) was considered the adverse outcome. Diagnostic performance was assessed at operating thresholds and by receiver operating characteristic (ROC) analysis, and the two indices were compared using the DeLong test (SPSS Statistics v23 (IBM Corp., Armonk, NY); MedCalc (Ostend, Belgium)). Results At a threshold of 1.2 breaths/min/mm, the D-RSBI showed strong diagnostic performance for successful weaning, with a sensitivity of 94.44% and specificity of 100% (area under the curve (AUC): 0.99, 95% confidence interval (CI): 0.97-1.00). The DTF discriminated poorly (sensitivity: 61.11%, specificity: 62.50%; AUC: 0.65, 95% CI: 0.42-0.88). The D-RSBI AUC was significantly higher than that of the DTF (DeLong p = 0.004). Notably, all eight patients with prolonged/failed weaning were also the eight most severely ill patients according to the Acute Physiology and Chronic Health Evaluation II score (APACHE II score, 13-21 vs. ≤ 10 in every patient who succeeded), and the direction of association for both indices was opposite to that reported in previous literature. Conclusions In this cohort, a D-RSBI ≥ 1.2 was strongly associated with successful weaning and outperformed the DTF. However, weaning outcome was completely determined by illness severity in this cohort, and the direction of the associations for both indices was inverted relative to prior studies. Therefore, these findings must be interpreted with caution and require validation in larger, multicenter cohorts.

Structural valve deterioration usually declares itself gradually, but a bioprosthetic leaflet that tears away from a stent post can produce catastrophic regurgitation without warning. In the mitral position, the left atrium has not had time to become compliant, and the resulting rise in pulmonary capillary pressure can flood the lungs within hours. A 68-year-old woman who had undergone mitral valve replacement with a bovine pericardial bioprosthesis 13 years earlier developed sudden dyspnea. Her oxygen saturation was 58%, the chest radiograph showed almost complete bilateral opacification, and the pH was 7.042 with a lactate of 8.8 mmol/L. She was intubated after noninvasive ventilation failed. Catheterization excluded coronary disease and showed a cardiac index of 1.32 L/minute/m², a mean pulmonary artery pressure of 35 mmHg, and a wedge pressure of 22 mmHg. Echocardiography demonstrated severe regurgitation through the prosthesis with an abnormally mobile leaflet. Emergency surgery was indicated, but the operating room was occupied, and a wait of several hours was expected. With the pulmonary artery pressure rising, an Impella CP (Abiomed, Danvers, MA) was implanted approximately 11 hours after arrival and supported the circulation for five hours until cardiopulmonary bypass was established. During that interval, the rise in pulmonary artery pressure did not continue; the cardiac index and mixed venous oxygen saturation increased, and oxygenation was maintained despite a reduction in the fraction of inspired oxygen. Mean pulmonary artery pressure nevertheless remained approximately 40 mmHg. One leaflet was found torn away from a stent post and prolapsing into the left atrium; the valve was replaced with a porcine bioprosthesis. Postoperatively, she required hemodiafiltration for acute kidney injury and temporary pacing for bradyarrhythmia; the course was further complicated by small cerebral infarcts and a right phrenic nerve palsy. She was extubated on day 10 and discharged home on day 48, remaining in New York Heart Association class I at review on day 108. When definitive surgery for acute left-sided valvular failure must be delayed for logistical reasons, temporary left ventricular unloading may be considered as a means of protecting the lung during the wait. In this patient, it was associated with maintained oxygenation and improved systemic hemodynamics, although its independent contribution cannot be determined from a single case.

Organizing pneumonia (OP) is a rare pulmonary manifestation in patients with inflammatory bowel disease (IBD). Distinguishing between a primary extra-intestinal manifestation of Crohn's disease (CD) and mesalazine-induced lung injury remains a major clinical challenge, as both conditions are steroid-responsive. We report the case of a 31-year-old woman with CD who developed progressive dyspnea and migratory pulmonary infiltrates one month after initiating mesalazine. Laboratory findings revealed marked peripheral eosinophilia (1276/mm3) and a mixed eosinophilic bronchoalveolar lavage profile (30.8%). Histopathology confirmed OP with Masson bodies. Due to the diagnostic overlap, mesalazine was replaced by azathioprine, and systemic corticosteroid therapy (0.75 mg/kg) was initiated. Complete radiological resolution was achieved at 8 months. This case illustrates the diagnostic complexity of eosinophilic-rich OP in CD and emphasizes that while pathology confirms the pattern, the etiology often remains a dual hypothesis between systemic disease and drug toxicity.

Earlier tissue-based studies report heterogeneous CYP and GST protein expression in non-small cell lung cancer (NSCLC), but simultaneous assessment of phase I and II enzymes in paired tumour and peripheral normal tissues remains limited and their expression patterns poorly characterised across the two major NSCLC histological subtypes, namely adenocarcinoma (AC) and squamous cell carcinoma (SCC). To address these gaps, this retrospective study evaluated CYP1A1, CYP1B1, CYP2E1, GSTM1, GSTT1, and GSTP1 expression immunohistochemically in tumour and peripheral normal lung tissues of 50 patients with NSCLC, 27 of whom with AC and 23 with SCC. Cytoplasmic staining intensity was scored from 0 to 3. Tissue and subtype comparisons were performed using the Mann-Whitney U test, and associations with clinical variables were assessed using Spearman's rank correlation. CYP2E1 expression was significantly higher in tumour than in normal tissue in the combined NSCLC group and in both histological subtypes (p<0.05). CYP1A1 expression was higher in AC tumours than in normal tissue and SCC tumours (both p<0.05). GSTM1 expression was higher in tumour tissue in the combined NSCLC group and in the SCC subgroup and was also higher in SCC than in AC tumours (p<0.05). GSTT1 expression was higher in AC than SCC tumours (p<0.05). CYP1B1 and GSTP1 were highly expressed in both tissue compartments but showed no significant tumour-specific increase. CYP and GST isoenzymes therefore showed tissue- and subtype-dependent rather than uniform expression patterns in NSCLC. The differences observed in CYP2E1, CYP1A1, GSTM1, and GSTT1 suggest that AC and SCC may differ in xenobiotic metabolism and cellular defence, and that these isoenzymes may contribute to metabolic processes associated with NSCLC pathogenesis.