Summary: SARS-CoV-2, the virus responsible for COVID-19, causes widespread damage in the lungs in the setting of an overzealous immune response whose origin remains unclear. We present a scalable, propagable, personalized, cost-effective adult stem cell-derived human lung organoid model that is complete with both proximal and distal airway epithelia. Monolayers derived from adult lung organoids (ALOs), primary airway cells, or hiPSC-derived alveolar type-II (AT2) pneumocytes were infected with SARS-CoV-2 to create in vitro lung models of COVID-19. Infected ALO-monolayers best recapitulated the transcriptomic signatures in diverse cohorts of COVID-19 patient-derived respiratory samples. The airway (proximal) cells were critical for sustained viral infection, whereas distal alveolar differentiation (AT2→AT1) was critical for mounting the overzealous host immune response in fatal disease; ALO monolayers with well-mixed proximodistal airway components recapitulated both. Findings validate a human lung model of COVID-19, which can be immediately utilized to investigate COVID-19 pathogenesis and vet new therapies and vaccines. GRAPHIC HIGHLIGHTS: Human lung organoids with mixed proximodistal epithelia are created Proximal airway cells are critical for viral infectivity Distal alveolar cells are important for emulating host response Both are required for the overzealous response in severe COVID-19 IN BRIEF: An integrated stem cell-based disease modeling and computational approach demonstrate how both proximal airway epithelium is critical for SARS-CoV-2 infectivity, but distal differentiation of alveolar pneumocytes is critical for simulating the overzealous host response in fatal COVID-19.

Surveillance donor-specific antibody (DSA) and pathologic antibody-mediated rejection (pAMR) testing is recommended in the first year after heart transplantation (HTx) in adult patients. Whether pAMR testing adds prognostic information to contemporary DSA testing has not been fully studied. This was a single-center study of consecutive endomyocardial biopsies (EMB) performed between November 2010 and February 2023 in adult HTx patients. The primary objective was to evaluate whether pAMR testing contributes additional information to DSA testing to better predict overall survival. Secondary end-points included cardiac survival and allograft dysfunction. A total of 6,033 EMBs from 544 HTx patients were reviewed for the study. The pAMR+/DSA+ patients had significantly lower overall (p_c = 0.013) and cardiac survival (p_c = 0.002), while the pAMR+/DSA- and pAMR-/DSA+ patients showed no difference in either outcome compared to the pAMR-/DSA- group. We found significantly lower overall survival in pAMR+/DSA+ patients with allograft dysfunction (p_c < 0.001) but not in pAMR+/DSA+ patients without allograft dysfunction (p_c = 0.569), when compared to the pAMR-/DSA- without allograft dysfunction group. The pAMR+/DSA+ patients with cardiac allograft dysfunction accounted for 18% of deaths or cardiac retransplants while only representing 4% of the HTx cohort. Moderate or severe primary graft dysfunction (PGD) also was a novel risk factor for the development of de novo DSAs (dnDSA) by 4 weeks post-HTx (p = 0.025). Surveillance DSA testing may effectively identify high-risk pAMR+ patients. Earlier DSA testing at 10 to 14 days post-HTx should also be considered in moderate or severe PGD patients.

Background: Bronchoscopic thermal ablation has emerged as a minimally invasive therapeutic option for managing pulmonary nodules in patients unsuitable for surgery or radiotherapy. Robotic-assisted bronchoscopy (RAB) offers enhanced stability and precise navigation, potentially improving the safety and accuracy of bronchoscopic ablation. However, clinical data on RAB-guided microwave ablation (MWA) remains limited. Therefore, further evidence is needed to evaluate its feasibility, safety, and early therapeutic performance. Methods: We conducted a single-center retrospective feasibility study of shape-sensing RAB-guided MWA (ssRAB-MWA) for pulmonary nodules between October 2024 and September 2025. Eligible lesions (≤3.0 cm) included both primary lung cancers and metastatic nodules. All procedures were performed under general anesthesia using the ssRAB system integrated with cone-beam CT for intra-procedural confirmation. Technical success, safety outcomes, and short-term efficacy were assessed. Results: Nine patients (with 11 lesions: 3 primary, 8 metastatic) underwent ssRAB-MWA with 100% technical success. The median ablation time per nodule was 10 min (range, 1–26). One patient developed post-ablation pneumonia requiring hospitalization; no pneumothorax, major bleeding, or airway injury occurred. All lesions exhibited a transient increase in size immediately following MWA, followed by gradual reduction or stabilization over time. PET-CT evaluation demonstrated metabolic remission in primary lesions, with one patient achieving pathologic complete response after surgery. Conclusions: ssRAB-MWA appears to be a feasible and safe navigation-guided technique for small pulmonary lesions, offering encouraging early local control in both primary and metastatic lung cancers. This platform may expand the therapeutic spectrum of interventional pulmonology, bridging diagnosis and local therapy. Larger multicenter studies are warranted to validate long-term outcomes.

Positive surgical margins (PSMs) are a major predictor of recurrence in thyroid cancer; however, their intraoperative detection remains challenging, particularly for microscopic PSMs. This study aimed to demonstrate that a sprayable pH-sensitive near-infrared fluorescent probe (PH10) could specifically and robustly label thyroid tumors in orthotopic mouse models. The pH sensitivity, cytotoxicity, and cellular uptake mechanisms of PH10 were evaluated in papillary thyroid carcinoma (K1) and anaplastic thyroid carcinoma (8505C) cell lines in vitro. Orthotopic thyroid cancer mouse models were then established using both K1 and 8505C cells. In vivo fluorescence following topical spraying of PH10 was quantified after sequential washes to assess tumor-to-background ratios. Fluorescence-guided surgery (FGS) was performed to determine whether PH10 could facilitate complete resection of orthotopically grown thyroid tumors. Complete resection was validated by hematoxylin and eosin histology. PH10 demonstrated low cytotoxicity at clinically relevant concentrations in vitro and showed selective uptake into thyroid cancer cells, predominantly via organic anion transporting polypeptide-mediated transport. Topical spraying of PH10 in orthotopic thyroid cancer mouse models established from K1 and 8505C cell lines generated strong tumor-specific fluorescence. Tumor-to-background ratios were significantly higher than background and remained distinguishable after multiple washes. In both models, PH10 enabled visualization of macroscopic residual tumors and detection of microscopic PSMs, with fluorescence patterns closely corresponding to histologic findings. FGS enabled complete tumor resection, as confirmed by fluorescence and histology. In conclusion, topical application of PH10 provides rapid, tumor-specific fluorescence suitable for identifying PSMs and facilitating complete tumor resection by FGS in thyroid cancer.

Mesothelial cell inclusions in cervical lymph nodes are of exceedingly rare occurrence and can be mistaken for metastatic adenocarcinoma. We report the case of a 27-year-old woman with a history of chronic myelogenous leukemia, diagnosed at age 5 years, and a recent diagnosis of alveolar soft part sarcoma of the left parotid gland. The patient underwent a left parotidectomy and neck dissection with intraoperative finding of abnormal lymph nodes in levels II to V. Histological examination revealed clusters of bland cells with pseudoglandular formation in 6 of 14 level IV/V lymph nodes. Immunological stains were consistent with mesothelial origin, and the diagnosis of benign mesothelial cell inclusions was made. Recognition of this entity in the evaluation of lymph nodes is important to prevent misdiagnosis of metastatic disease, particularly in a patient with multiple known malignancies.