A Consistent Endoscopic Landmark to Identify the Anterior Ethmoidal Artery.

OBJECTIVE: The anterior ethmoidal artery (AEA) is an important structure to identify during endoscopic sinus surgery. Although identification on imaging is easily taught, a consistent endoscopic landmark for the AEA, independent of anatomic ethmoid cell variation, is lacking, leaving many surgeons unclear about the exact location without dependence on navigation. Here, we describe a consistent endoscopic landmark, regardless of anatomical ethmoid variation. METHODS: We prospectively enrolled adult patients undergoing endoscopic surgery involving frontal and ethmoid sinuses in this observational study. The AEA landmark was defined simply as the septation or ridge one step back along the ethmoid skull base from the posterior table of the frontal sinus. The gold standard to calculate the sensitivity of our endoscopic landmark was an image-navigation system, registered to within 1.5 mm accuracy, locating the AEA within three planes. Both endoscopic and computerized tomography (CT) images of the pointer at the landmark were taken simultaneously. The concordance of endoscopic to navigation images was independently assessed by three blinded rhinologists. RESULTS: Forty patients were included in our study with 73 sides analyzed. Diagnoses included chronic rhinosinusitis without polyps (52.5%), with polyps (22.5%), recurrent acute sinusitis (15%), sinonasal tumors (7.5%), and odontogenic sinusitis (2.5%). The AEA was accurately identified using our endoscopic landmark in 97.3% of the cases (71/73). Of the two cases in which the AEA was not found within the landmark, the artery was located ≤1 mm posteriorly. CONCLUSION: We describe a consistent endoscopic landmark to identify the AEA, conserved across various clinical diagnoses and anatomic variations in sinus structure. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1096-1099, 2024.

A Rare Case of Neurosyphilis with Calvaria Osteitis Presenting in Pregnancy.

Background: The incidence of syphilis throughout the world is increasing. Rates in pregnancy are similarly rising, presenting risks of an untreated syphilis infection that can be detrimental to the mother and fetus. Although routine screening for syphilis infections is recommended at the initial prenatal visit, there is a lack of universal agreement on rescreening pregnant people and approximately 50% of syphilis cases are asymptomatic in the general population. Furthermore, some symptoms of syphilis can overlap with nonspecific pregnancy-related symptoms. Meanwhile, Treponema pallidum can spread to various maternal and fetoplacental tissues quickly after infection and occur at any stage of syphilis. Case: A 26-year-old gravida 5 para 2 presented with a new onset headache and visual and auditory changes at 23 weeks of gestation. A computerized tomography scan revealed numerous ill-defined lytic lesions throughout the calvarium, suspicious for syphilitic osteitis. She tested positive for syphilis antibodies with a rapid plasma reagin (RPR) titer of 1 : 32. Cerebrospinal fluid evaluation from a lumbar puncture resulted in reactive fluorescent treponemal antibody (FTA) testing. She was diagnosed with secondary syphilis with osteitis and neuro and otic components. She completed 14 days of intravenous aqueous crystalline penicillin G with additional benzathine penicillin G 2.4 million units intramuscular weekly for two weeks. There was no evidence of congenital syphilis on neonatal examination. Conclusion: Syphilitic osteitis and neuro, otic, or ocular syphilis infections occur rarely in the nonpregnant population, and therefore, little data in pregnancy is available to inform outcomes in these specific disease states. It is of paramount importance to complete appropriate syphilis screening, recognize symptoms, and consider utilizing rescreen protocols to ensure prompt infection identification and treatment. For neuro, otic, and ocular syphilis, aqueous crystalline penicillin G (as opposed to benzathine penicillin G) is required to achieve treponemicidal concentrations in those physiologic compartments. There is no agreement as to the appropriate treatment regimen for the rare finding of syphilitic osteitis.

In Situ-Forming Collagen-Hyaluronate Semi-Interpenetrating Network Hydrogel Enhances Corneal Defect Repair.

Purpose: Millions worldwide suffer vision impairment or blindness from corneal injury, and there remains an urgent need for a more effective and accessible way to treat corneal defects. We have designed and characterized an in situ-forming semi-interpenetrating polymer network (SIPN) hydrogel using biomaterials widely used in ophthalmology and medicine. Methods: The SIPN was formed by cross-linking collagen type I with bifunctional polyethylene glycol using N-hydroxysuccinimide ester chemistry in the presence of linear hyaluronic acid (HA). Gelation time and the mechanical, optical, swelling, and degradation properties of the SIPN were assessed. Cytocompatibility with human corneal epithelial cells and corneal stromal stem cells (CSSCs) was determined in vitro, as was the spatial distribution of encapsulated CSSCs within the SIPN. In vivo wound healing was evaluated by multimodal imaging in an anterior lamellar keratectomy injury model in rabbits, followed by immunohistochemical analysis of treated and untreated tissues. Results: The collagen-hyaluronate SIPN formed in situ without an external energy source and demonstrated mechanical and optical properties similar to the cornea. It was biocompatible with human corneal cells, enhancing CSSC viability when compared with collagen gel controls and preventing encapsulated CSSC sedimentation. In vivo application of the SIPN significantly reduced stromal defect size compared with controls after 7 days and promoted multilayered epithelial regeneration. Conclusions: This in situ-forming SIPN hydrogel may be a promising alternative to keratoplasty and represents a step toward expanding treatment options for patients suffering from corneal injury. Translational Relevance: We detail the synthesis and initial characterization of an SIPN hydrogel as a potential alternative to lamellar keratoplasty and a tunable platform for further development in corneal tissue engineering and therapeutic cell delivery.

Landscape of innate lymphoid cells in human head and neck cancer reveals divergent NK cell states in the tumor microenvironment.

Natural killer (NK) cells comprise one subset of the innate lymphoid cell (ILC) family. Despite reported antitumor functions of NK cells, their tangible contribution to tumor control in humans remains controversial. This is due to incomplete understanding of the NK cell states within the tumor microenvironment (TME). Here, we demonstrate that peripheral circulating NK cells differentiate down two divergent pathways within the TME, resulting in different end states. One resembles intraepithelial ILC1s (ieILC1) and possesses potent in vivo antitumor activity. The other expresses genes associated with immune hyporesponsiveness and has poor antitumor functional capacity. Interleukin-15 (IL-15) and direct contact between the tumor cells and NK cells are required for the differentiation into CD49a+CD103+ cells, resembling ieILC1s. These data explain the similarity between ieILC1s and tissue-resident NK cells, provide insight into the origin of ieILC1s, and identify the ieILC1-like cell state within the TME to be the NK cell phenotype with the greatest antitumor activity. Because the proportions of the different ILC states vary between tumors, these findings provide a resource for the clinical study of innate immune responses against tumors and the design of novel therapy.

3D Printable, Modified Trephine Designs for Consistent Anterior Lamellar Keratectomy Wounds in Rabbits.

PURPOSE: Our goal is to develop a low-cost tool that can be used to create consistent, partial-thickness defects in rabbit and other large animals with minimal surgical training and that can facilitate pre-clinical testing of lamellar and in situ-forming biosynthetic matrix materials for corneal repair. MATERIALS & METHODS: In this study, three modified trephines were designed to create deep corneal wound defects with consistent depth in large animals. The modified trephines incorporated either 3D-printed parts made from photopolymerizable resins, or custom-cut commercially available Teflon sheets. Wound defects were imaged with optical coherence tomography (OCT), and the depth was analyzed based on the OCT images. RESULTS: The results revealed that an inner-stopper guard trephine had the best performance in creating consistent and precise wound defect depth compared to modified vacuum trephine and custom guard vacuum trephine. A 75% ± 10% cut of the cornea was achieved with the inner-stopper guard trephine. The wound defect depth by created by the inner-stopper guard trephine was independent of the corneal thickness or size of the globes. Although the cut depth of the inner-stopper guard trephine differed by the experience-level of its users, the consistency (standard deviation) of the depth was independent of experience. CONCLUSIONS: Our studies provided three cost-efficient animal trephines that can create corneal wounds of consistent depth by lab researchers without extensive training in keratectomy.

The use of platelet-rich plasma in treatment of olfactory dysfunction: A pilot study.

BACKGROUND: Olfactory dysfunction is a prevalent problem with a significant impact on quality of life and increased mortality. Limited effective therapies exist. Platelet-rich plasma (PRP) is an autologous biologic product with anti-inflammatory and neuroprotective effects. This novel pilot study evaluated the role of PRP on olfactory neuroregeneration in patients with hyposmia. METHODS: Seven patients who had olfactory loss greater than 6 months in duration, no evidence of sinonasal inflammatory disease, and no improvement with olfactory training and budesonide topical rinses were enrolled in this preliminary study. Patients received a single intranasal injection of PRP into the mucosa of the olfactory cleft. The Sniffin' Sticks olfactory test consisting of threshold, discrimination, and identification measurements (TDI) was administered at the beginning of the study and at 1 and 3 months. RESULTS: All patients reported a subjective improvement of their smell shortly after injection but then stabilized. At 3-month post-treatment, two patients with functional anosmia (TDI < 16) did not improve significantly. Five patients with hyposmia (TDI > 16 but <30) showed an improvement with 60% achieving normosmia (TDI > 30) at 3-month follow-up. On average, patients with baseline TDI > 16 improved by 5.85 points with the most significant improvement in the threshold subcomponent. There were no adverse outcomes from intranasal PRP injections. CONCLUSION: PRP appears safe for use in the treatment of olfactory loss, and preliminary data suggest possible efficacy, especially for those with moderate yet persistent loss. Further studies will help determine optimal frequency and duration of use.

Assessing the Impact of Targeting CEACAM1 in Head and Neck Squamous Cell Carcinoma.

Objective In conjunction with advances made in cytotoxic chemotherapy, radiation, and surgery, immunotherapy has emerged as a fourth modality of treatment for head and neck squamous cell carcinoma (HNSCC). Understanding the mechanisms by which HNSCC evades immune-mediated control will aid in the development of new therapies to augment an antitumor immune response. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a cell surface receptor that is expressed on malignant cells and lymphocytes such as natural killer (NK) cells. We sought to determine whether tumor-derived CEACAM1 inhibits NK cell cytotoxicity and whether blockade of CEACAM1 restores antitumor immunity. Study Design In vitro HNSCC cell line study. Setting Research laboratory. Subject and Methods We utilized a real-time cell analyzer to assess NK cell cytotoxicity against an oral squamous cell carcinoma cell line after modulating CEACAM1 expression by cytokines and shRNA knockdown of CEACAM1 expression. Results NK cells and HNSCC cells both demonstrated cytokine-inducible expression of CEACAM1. Coincubation of NK cells and HNSCC cells resulted in the upregulation of CEACAM1 on the tumor cells. When compared with CEACAM1- cells, CEACAM1+ tumor cells exhibited increased cell growth and increased size and number of organoids in 3-dimensional culture. Notably, CEACAM1+ HNSCC cells were more resistant to NK cell-mediated killing, but the inhibited expression of CEACAM1 by an shRNA construct restored NK cell cytotoxicity. Conclusion Together, these data indicate that CEACAM1 acts as an inducible checkpoint molecule, and they support the idea that targeting CEACAM1 could serve as a novel immunotherapy approach in HNSCC.

The aryl hydrocarbon receptor modulates the function of human CD56bright NK cells.

Human natural killer (NK) cells are divided into two subsets: CD56bright and CD56dim NK cells, which differ in maturation, function and distribution. Mechanisms regulating NK cell functions are not completely understood. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, that binds to a variety of endogenous and exogenous molecules, and that has recently been shown to modulate the function and differentiation of immune cells. Here, we studied the expression of AhR and its involvement in the regulation of NK cell functions. We found that AhR mRNA is highly expressed in peripheral CD56bright NK cells and that AhR mRNA expression gradually decreases as NK cells display a more mature phenotype. CD56bright NK cells were highly sensitive to AhR ligands. Specifically, AhR ligands modulated their activation and their expression of NK cell receptors, as well as cytokine secretion which is the major function of these cells. As CD56bright NK cells are highly enriched in tissues and in tumors, our observations point to a possible effect of local AhR ligands in the regulation of the function of CD56bright tissue-resident or intratumoral NK cells.

Combining phenobarbital and indomethacin to improve early neonatal outcomes in the extremely low birth weight infant.

In this retrospective study, we tested the following hypotheses: rates of severe intraventricular hemorrhage (SIVH) and early neonatal survival are similar among extremely low birth weight (ELBW) infants treated with combination prophylaxis of phenobarbital and indomethacin compared with phenobarbital alone or no prophylaxis; and rates of patent ductus arteriosus (PDA) and necrotizing enterocolitis (NEC) are similar among indomethacin-exposed and nonexposed ELBW infants. Data were abstracted on 265 ELBW infants admitted into a level 3 neonatal intensive care unit from 1994 through 2002. Combination prophylaxis neither reduced the odds ratio (OR) of SIVH (OR = 1.53; 95% confidence interval [CI], 0.43 to 1.16) versus phenobarbital (OR = 2.91; 95% CI, 0.91 to 9.27 versus none (OR = 1; 95% CI, reference) nor increased the odds of early neonatal survival (OR = 0.72; 95% CI, 0.17 to 3.09 for combination prophylaxis versus OR = 0.66; 95% CI, 0.16 to 2.67 for phenobarbital versus OR = 1; 95% CI, reference for none). Indomethacin exposure reduced the odds of PDA (OR = 0.35; 95% CI, 0.17 to 0.75) without increasing the risk of NEC (OR = 1.37; 95% CI, 0.60 to 3.12). In conclusion, combination prophylaxis does not improve SIVH and early neonatal survival outcomes. Early exposure to indomethacin offers some benefits without any added risks.

Role of mental illness in drug use by urban pregnant heavy smokers.

The object of the study was to test the hypothesis that mental illness is associated with drug abuse by pregnant smokers. We abstracted data from the State of Missouri Risk Appraisal of Pregnant Women database on 239 (115 black and 124 white) women who attended an inner-city hospital from 1999 through 2000. Thirty-four percent abused drugs, 16% used alcohol, and 8% reported having a history of mental illness or psychiatric treatment. On multivariable logistic regression analyses, pregnant smokers were more likely to use drugs if they had mental illness (odds ration [OR], 7), consumed alcohol (OR, 2), or were black (OR, 3). In conclusion, drug abuse is associated with mental illness, suggesting that this behavior may be a marker of underlying mental illness among pregnant smokers. Therefore, in addition to initiating social service intervention, the identification of drug abuse by pregnant smokers should prompt a mental health evaluation.