Exosome Therapy for a Nonhealing Scalp Wound Following Chemoradiation and Surgical Therapy.

This case report describes the safety and utility of a noninvasive therapy, Purified Exosome Product (PEP), for poorly healing scalp wounds in the setting of prior chemoradiation and surgery. A man in his 60s with a history of high-grade angiosarcoma of the right temporoparietal scalp reconstruction had a 1-year history of 2 nonhealing scalp wounds after neoadjuvant chemotherapy followed by concurrent chemoradiation therapy, wide local excision, and latissimus dorsi free flap and split-thickness skin graft. The patient underwent débridement followed by 4 collagen (Bellafill)-PEP and 4 fibrin (Tisseel)-PEP applications during 7 months in 2022. Photographs of the area of exposed bone of the temporoparietal wound were measured and standardized by ImageJ open-source software. The frontal wound was not routinely measured and therefore was qualitatively assessed by reviewing photographs over time. The frontal wound completely healed, and the temporoparietal wound showed a 96% decrease in overall size. The patient had no adverse effects of treatment and continues to demonstrate ongoing healing. This case exhibits the safety and utility of topical PEP therapy for noninvasive treatment of poorly healing scalp wounds and offers the potential for an alternative treatment of patients who are poor candidates for additional surgical intervention.

Third window lesions of the inner ear: A pictorial review.

PURPOSE: Radiographic review of pathologies that associate with third window syndrome. METHODS: Case series and literature review. RESULTS: Eight unique third window conditions are described and illustrated, including superior, lateral, and posterior semicircular canal dehiscence; carotid-cochlear, facial-cochlear, and internal auditory canal-cochlear dehiscence, labyrinthine erosion from endolymphatic sac tumor, and enlarged vestibular aqueduct. CONCLUSION: The present study highlights the characteristic imaging features and symptoms to differentiate third window pathologies for expedient diagnosis and management planning.

State of the Art Medical Management of Nasal Polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease with a treatment goal of controlling symptoms and limiting disease burden. While endoscopic sinus surgery is effective for removing polyps and aerating sinuses, proper medical management remains necessary for reducing inflammation and limiting polyp recurrence. OBJECTIVE: This article aims to summarize the literature regarding medical treatment of chronic rhinosinusitis with nasal polyposis, with a specific focus on developments in the past 5 years. METHODOLOGY: We conducted a literature review using PubMed to identify studies assessing medical treatment strategies for patients with CRSwNP. Articles focusing on chronic rhinosinusitis without nasal polyposis were excluded unless specifically stated. Surgical treatment and biologic therapies for CRSwNP will be covered in subsequent chapters and are therefore not included. RESULTS: Intranasal saline irrigations and topical steroids are mainstays of CRSwNP treatment in the pre-surgical, post-surgical, and maintenance phases of the disease. Alternative steroid delivery methods and adjunctive treatments with antibiotics, anti-leukotrienes, and other topical therapies have been investigated and may benefit certain patient populations, but convincing evidence does not exist to warrant addition of these treatments to the standard of care for CRSwNP. CONCLUSIONS: Topical steroid therapy is clearly effective for CRSwNP, and recent studies demonstrate the safety and efficacy of high-dose nasal steroid rinses. Alternate delivery methods for local steroids may be useful for patients who are not responding to or who are noncompliant with conventional intranasal corticosteroid sprays and rinses. Future studies are needed to clarify if oral or topical antibiotics, oral anti-leukotrienes, or other novel therapies are significantly effective in decreasing symptoms and improving the quality of life in patients with CRSwNP.

Inflammatory Monocytes Drive Influenza A Virus-Mediated Lung Injury in Juvenile Mice.

Healthy children are more likely to die of influenza A virus (IAV) infection than healthy adults. However, little is known about the mechanisms underlying the impact of young age on the development of life-threatening IAV infection. We report increased mortality in juvenile mice compared with adult mice at each infectious dose of IAV. Juvenile mice had sustained elevation of type I IFNs and persistent NLRP3 inflammasome activation in the lungs, both of which were independent of viral titer. Juvenile mice, but not adult mice, had increased MCP-1 levels that remained high even after viral clearance. Importantly, continued production of MCP-1 was associated with persistent recruitment of monocytes to the lungs and prolonged elevation of inflammatory cytokines. Transcriptional signatures of recruited monocytes to the juvenile and adult IAV-infected lungs were assessed by RNA-seq. Genes associated with a proinflammatory signature were upregulated in the juvenile monocytes compared with adult monocytes. Depletion of monocytes with anti-CCR2 Ab decreased type I IFN secretion, NLRP3 inflammasome activation, and lung injury in juvenile mice. This suggests an exaggerated inflammatory response mediated by increased recruitment of monocytes to the lung, and not an inability to control viral replication, is responsible for severe IAV infection in juvenile mice. This study provides insight into severe IAV infection in juveniles and identifies key inflammatory monocytes that may be central to pediatric acute lung injury secondary to IAV.

Inhibition of the NOD-Like Receptor Protein 3 Inflammasome Is Protective in Juvenile Influenza A Virus Infection.

Influenza A virus (IAV) is a significant cause of life-threatening lower respiratory tract infections in children. Antiviral therapy is the mainstay of treatment, but its effectiveness in this age group has been questioned. In addition, damage inflicted on the lungs by the immune response to the virus may be as important to the development of severe lung injury during IAV infection as the cytotoxic effects of the virus itself. A crucial step in the immune response to IAV is activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and the subsequent secretion of the inflammatory cytokines, interleukin-1ß (IL-1ß), and interleukin-18 (IL-18). The IAV matrix 2 proton channel (M2) has been shown to be an important activator of the NLRP3 inflammasome during IAV infection. We sought to interrupt this ion channel-mediated activation of the NLRP3 inflammasome through inhibition of NLRP3 or the cytokine downstream from its activation, IL-1ß. Using our juvenile mouse model of IAV infection, we show that inhibition of the NLRP3 inflammasome with the small molecule inhibitor, MCC950, beginning 3 days after infection with IAV, improves survival in juvenile mice. Treatment with MCC950 reduces NLRP3 levels in lung homogenates, decreases IL-18 secretion into the alveolar space, and inhibits NLRP3 inflammasome activation in alveolar macrophages. Importantly, inhibition of the NLRP3 inflammasome with MCC950 does not impair viral clearance. In contrast, inhibition of IL-1ß signaling with the IL-1 receptor antagonist, anakinra, is insufficient to protect juvenile mice from IAV. Our findings suggest that targeting the NLRP3 inflammasome in juvenile IAV infection may improve disease outcomes in this age group.

Influenza A Virus Infection, Innate Immunity, and Childhood.

Infection with influenza A virus is responsible for considerable morbidity and mortality in children worldwide. While it is apparent that adequate activation of the innate immune system is essential for pathogen clearance and host survival, an excessive inflammatory response to infection is detrimental to the young host. A review of the literature indicates that innate immune responses change throughout childhood. Whether these changes are genetically programmed or triggered by environmental cues is unknown. The objectives of this review are to summarize the role of innate immunity in influenza A virus infection in the young child and to highlight possible differences between children and adults that may make children more susceptible to severe influenza A infection. A better understanding of age-related differences in innate immune signaling will be essential to improve care for this high-risk population.