Phagocytosis of apoptotic cells and cellular debris is a critical process of maintaining tissue and immune homeostasis. Defects in the phagocytosis process cause autoimmunity and degenerative diseases. Phagocytosis ligands or “eat-me” signals control the initiation of the process by linking apoptotic cells to receptors on phagocyte surface and triggering signaling cascades for cargo engulfment. Eat-me signals are traditionally identified on a case-by-case basis with challenges, and the identification of their cognate receptors is equally daunting. Here we identified galectin-3 (Gal-3) as a new MerTK ligand by an advanced dual functional cloning strategy, in which phagocytosis-based functional cloning is combined with receptor-based affinity cloning to directly identify receptor-specific eat-me signal. Gal-3 interaction with MerTK was independently verified by co-immunoprecipitation. Functional analyses showed that Gal-3 stimulates the phagocytosis of apoptotic cells and cellular debris by macrophages and retinal pigment epithelial cells with MerTK activation and autophosphorylation. The Gal-3-mediated phagocytosis was blocked by excessive soluble MerTK extracellular domain and lactose. These results suggest that Gal-3 is a legitimate MerTK-specific eat-me signal. The strategy of dual functional cloning with applicability to other phagocytic receptors will facilitate unbiased identification of their unknown ligands and improve our capacity for therapeutic modulation of phagocytic activity and innate immune response.
Introduction
Augmented reality (AR) fuses computer-generated images of preoperative imaging data with real-time views of the surgical field. Scopis Hybrid Navigation (Scopis, GmbH, Berlin, Germany) is a surgical navigation system with AR capabilities for endoscopic sinus surgery (ESS).
Methods
Pre-dissection planning was performed with Scopis Hybrid Navigation software followed by ESS dissection on 2 human specimens using conventional ESS instruments.
Results
Pre-dissection planning included creating models of relevant frontal recess structures and the frontal sinus outflow pathway on orthogonal CT images. Positions of the optic nerve and internal carotid artery were marked on the CT images. Models and annotations were displayed as an overlay on the endoscopic images during the dissection, which was performed with electromagnetic surgical navigation. The accuracy of the AR images relative to underlying anatomy was better than 1.5 mm. The software's trajectory targeting tool was used to guide instrument placement along the frontal sinus outflow pathway. AR imaging of the optic nerve and internal carotid artery served to mark the positions of these structures during the dissection.
Conclusions
Surgical navigation with AR was easily deployed in this cadaveric model of ESS. This technology builds upon the positive impact of surgical navigation during ESS, particularly during frontal recess surgery. Instrument tracking with this technology facilitates identifying and cannulation of the frontal sinus outflow pathway without dissection of the frontal recess anatomy. AR can also highlight “anti-targets” (i.e., structures to be avoided), such as the optic nerve and internal carotid artery, and thus reduce surgical complications and morbidity.
Thyroglossal duct cyst carcinoma is uncommon and management is controversial. In low-risk patients (single tumor focus, negative margins, normal preoperative neck/thyroid imaging, no extension of TGDC carcinoma beyond the cyst wall), the Sistrunk procedure alone with observation of the thyroid may be sufficient. In this patient population, RAI is unlikely to be of any substantial benefit.
Significant dysphagia, pain, and risk of bleeding occur after transoral robotic surgery (TORS) radical tonsillectomy. We present a novel surgical technique utilizing robotically assisted submandibular gland transposition (SMGT) to reconstruct the radical tonsillar defect. A 48‐year‐old male with p16+ tonsillar squamous cell carcinoma underwent deep TORS radical tonsillectomy, contralateral tonsillectomy, ipsilateral neck dissection, and TORS‐assisted reconstruction of the radical defect with ipsilateral SMGT. Postoperatively, the patient experienced minimal pain and was discharged on postoperative day (POD) 3 tolerating a soft diet. There were no episodes of postoperative bleeding. This procedure was performed in five other cases as well. Transoral robotic SMGT can be used successfully to repair deep TORS radical tonsillectomy defects and may theoretically reduce dysphagia, pain, and the risk of hemorrhage.
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