Smoke inhalation associated with structural fires, wildfires, or explosions leads to lung injury, for which innovative and clinically relevant animal models are needed to develop effective therapeutics. We have previously reported that damage-associated molecular patterns (DAMPs) and anti-inflammatory cytokines correlate with infectious complications in patients diagnosed with inhalational injury. In this study, we describe a novel and translational murine model of acute inhalational injury characterized by an accumulation of protein and neutrophils in the bronchoalveolar space, as well as histological evidence of tissue damage. Mice were anesthetized, and a cannula was placed in the trachea and exposed to smoldering plywood smoke three times for 2-min intervals in a smoke chamber. Here we demonstrate that this model recapitulates clinically relevant phenotypes, including early release of double-stranded DNA (dsDNA), IL-10, monocyte chemoattractant protein (MCP)-1, and CXCL1 along with neutrophilia early after injury, accompanied by subsequent susceptibility to opportunistic infection with Pseudomonas aeruginosa. Further investigation of the model, and in turn a reanalysis of patient samples, revealed a late release of the DAMP hyaluronic acid (HA) from the lung. Using nitric oxide synthase-deficient mice, we found that Nos2 was required for increases in IL-10, MCP-1, and HA following injury but not release of dsDNA, CXCL1 expression, early neutrophilia, or susceptibility to opportunistic infection. Depletion of CXCL1 attenuated early neutrophil recruitment, leading to decreased histopathology scores and improved bacterial clearance in this model of smoke inhalation. Together, these data highlight the potential therapeutic benefit of attenuating neutrophil recruitment in the first 24 h after injury in patients.

BACKGROUND:No methods exist to rapidly and accurately quantify the immune insult created by burn injuries. The development of a rapid, noninvasive clinical biomarker assay that evaluates a burn patient's underlying immune dysfunction and predicts clinical outcomes could transform burn care. We aimed to determine a set of peripheral biomarkers that correlates with clinical outcomes of burn patients. METHODS:This prospective observational study enrolled two patient cohorts within a single burn center into an institutionally approved institutional review board study. Blood draws were performed <48 hours after injury. Initial unbiased immune gene expression analysis compared 23 burn patients and 6 healthy controls using multiplex immune gene expression analysis of RNA from peripheral blood mononuclear cells. We then performed confirmatory outcomes analysis in 109 burn patients and 19 healthy controls using a targeted rapid quantitative polymerase chain reaction. Findings were validated and modeled associations with clinical outcomes using a regression model. RESULTS:A total of 149 genes with a significant difference in expression from burn patients compared with controls were identified. Pathway analysis identified pathways related to interleukin (IL)-10 and inducible nitric oxide synthase signaling to have significant z scores. quantitative polymerase chain reaction analysis of IL-10, IL-12, arginase 1 (ARG1), and inducible nitric oxide synthase demonstrated that burn injury was associated with increased expression of ARG1 and IL-10, and decreased expression of nitric oxide synthase 2 (NOS2) and IL-12. Burn severity, acute lung injury, development of infection, failure of skin autograft, and mortality significantly correlated with expression of one or more of these genes. Ratios of IL-10/IL-12, ARG1/NOS2, and (ARG1-IL-10)/ (NOS2-IL-12) transcript levels further improved the correlation with outcomes. Using a multivariate regression model, adjusting for patient confounders demonstrated that (ARG1-IL-10)/(NOS2-IL-12) significantly correlated with burn severity and development of acute lung injury. CONCLUSION:We present a means to predict patient outcomes early after burn injury using peripheral blood, allowing early identification of underlying immune dysfunction.

Background Aspirin-exacerbated respiratory disease (AERD) is characterized by excessive leukotriene production, diffuse polyp burden and osteitic bone changes. These bony changes have not been previously characterized. Objective The aim of this radiographic study is to characterize the bony changes noted on computed tomography (CT) scans of the sphenoid sinus in patients with AERD compared to other diseased sinonasal inflammatory states and non-diseased controls. Methods A retrospective review of 43 patients with clinically confirmed AERD were included and compared to 22 non-diseased, 9 allergic fungal sinusitis, and 43 chronic rhinosinusitis controls (23 without polyps and 18 with polyps). Comparative measurements were performed using fine-cut CT scans. Sites of comparison were the intersinus septum, the left and right lateral sphenoid wall, the roof, and left and right floor of the sphenoid sinus. Standardized measurements were averaged by two separate rhinologists. Results Patients with AERD had an average statistically significant increase in bone thickness compared to healthy and diseased controls in nearly every site with the most pronounced changes in the intersinus septum (p < 0.05). Conclusion Patients with AERD have significantly increased thickness of the sphenoid bone compared to control groups with the most pronounced difference in the intersinus septum. These findings may help clinicians increase suspicion for a diagnosis of AERD who clinically have diffuse nasal polyposis.

BackgroundHyalinizing clear cell carcinomas (HCCCs) are rare, low-grade, malignant tumors which most often arise from the minor salivary glands primarily in palate and tongue but can arise in any location with minor salivary glands including the nasopharynx.MethodsA case report of primary nasopharyngeal HCCC is presented. Because of the rarity of this tumor and location, a literature search was conducted to determine the most common presenting symptoms, treatment strategies, and outcomes.ResultsA 48-year-old man underwent biopsy of a 4.5 cm mass of the right nasopharynx with pathology suggesting an intermediate grade mucoepidermoid carcinoma. After discussing management with the patient, an endoscopic resection was performed. Final pathology revealed an HCCC which was confirmed after negative Mastermind-like 2 (MAML2) and positive Ewing sarcoma breakpoint region 1 (ESWR1) gene rearrangements on fluorescence in situ hybridization (FISH) studies. Literature review of other nasopharyngeal HCCC cases shows diverse presentation and overall excellent prognosis through surgical and radiation therapy.ConclusionHCCCs are rare, low-grade malignant tumors of the minor salivary glands and can present as a nasopharyngeal mass. Presenting symptoms are diverse but frequently involve otologic and sinonasal disturbances. HCCC is an indolent tumor with an excellent prognostic outcome when treated appropriately with surgical resection and adjuvant radiotherapy.

Background:  Manouguian aortic root enlargement (ARE) has been a standard root enlargement procedure to assist in patients with a small annular size. We describe a modification to the Manouguian ARE similar to Yang et al. This approach could serve as an alternate technique for performing ARE; to date only case reports have defined this approach and no studies have evaluated its efficacy or safety. Methods:  A retrospective case series was performed on patients who underwent ARE for surgical aortic valve replacement via the modified Manouguian procedure at a single institution. Thirteen patients were identified between 2015-2021, and all surgeries were performed by a single operator. Data were collected via the Society of Thoracic Surgeons database and chart review. The primary outcome was difference in valve size after the procedure.  Results:  The most common indication for surgery was aortic stenosis (12, 92%), with the most common etiology being degenerative calcification (7, 54%). Congenital bicuspid or uni-cuspid valves were identified in 5 (38%) patients. The majority (10, 77%) of patients received a mechanical valve. This procedure was successfully performed in all 13 of the patients. Additionally, 13 of the 13 patients (100%) were upsized to a satisfactory valve size based on pre-operative echocardiography sizing. Conclusions:  The modified Manouguian aortic enlargement technique can be safely and effectively used as an aortic enlargement procedure in a broad sample of patients.