Radiotherapy for head and neck cancers commonly causes damage to salivary gland tissue, resulting in xerostomia (dry mouth) and numerous adverse medical and quality-of-life issues. Amifostine is the only Food and Drug Administration-approved radioprotective drug used clinically to prevent xerostomia. However, systemic administration of amifostine is limited by severe side effects, including rapid decrease in blood pressure (hypotension), nausea, and a narrow therapeutic window. In this study, we demonstrate that retroductal delivery of amifostine and its active metabolite, WR-1065, to murine submandibular glands prior to a single radiation dose of 15 Gy maintained gland function and significantly increased acinar cell survival. Furthermore, in vivo stimulated saliva secretion was maintained in retrograde-treated groups at levels significantly higher than irradiated-only and systemically treated groups. In contrast to intravenous injections, retroductal delivery of WR-1065 or amifostine significantly attenuated hypotension. We conclude that localized delivery to salivary glands markedly improves radioprotection at the cellular level, as well as mitigates the adverse side effects associated with systemic administration. These results support the further development of a localized delivery system that would be compatible with the fractionated dose regimen used clinically.
Introduction: Image-guided surgery (IGS) has gained widespread acceptance in otorhinolaryngology for its applications in sinus and skull base surgery. Although the core concepts of IGS have not changed, advances in image guidance technology, including the incorporation of intraoperative imaging, have the potential to enhance surgical education, allow for more rigorous preoperative planning, and aid in more complete surgery with improved outcomes. Objectives: Provide a clinical update regarding the use of image guidance and intraoperative imaging in the field of rhinology and endoscopic skull base surgery with a focus on current state of the art technologies. Methods: English-language studies published in PubMed, Cochrane, and Embase were searched for articles relating to image-guided sinus surgery, skull base surgery, and intraoperative imaging. Relevant studies were reviewed and critical appraisals were included in this clinical update, highlighting current state of the art advances. Conclusions: As image guidance and intraoperative imaging systems have advanced, their applications in sinus and skull base surgery have expanded. Both technologies offer invaluable real-time feedback on the status and progress of surgery, and thus may help to improve the completeness of surgery and overall outcomes. Recent advances such as augmented and virtual reality offer a window into the future of IGS. Future advancements should aim to enhance the surgeon’s operative experience by improving user satisfaction and ultimately lead to better surgical results.
In the last two decades, the development of culture-independent genomic techniques has facilitated an increased appreciation of the microbiota-immunity interactions and their role in a multitude of chronic inflammatory diseases such as chronic rhinosinusitis (CRS), asthma, inflammatory bowel disease and dermatitis. While the pathologic role of bacteria in chronic inflammatory diseases is generally accepted, the understanding of the role of fungi remains controversial. Chronic rhinosinusitis, specifically the phenotype linked to nasal polyps, represents a spectrum of chronic inflammatory diseases typically characterized by a type 2 immune response. Studies on the microbiota within sinus cavities from healthy and diseased patients have focused on the bacterial community, mainly highlighting the loss of diversity associated with sinus inflammation. Within the various CRS with nasal polyps (CRSwNP) phenotypes, allergic fungal rhinosinusitis presents an opportunity to investigate the role of fungi in chronic type 2 immune responses as well as the antifungal immune pathways designed to prevent invasive fungal diseases. In this review, we examine the spectrum of fungiassociated sinus diseases highlighting the interaction between fungal species and host immune status on disease presentation. With a focus on fungi and type 2 immune response, we highlight the current knowledge and its limitations of the sinus mycobiota along with cellular interactions and activated molecular pathways linked to fungi.
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