Nasal Epistaxis Balloons: A Comprehensive MAUDE Database Analysis.

BACKGROUND: While nasal epistaxis balloons are generally seen as safe and routinely utilized by both surgical and nonsurgical providers, the complication profile related to this type of device has not been well defined. OBJECTIVE: The objective of this study was to utilize the FDA MAUDE (Manufacturer and User Facility Device Experience) database to better assess adverse events (AE) related to use of nasal epistaxis balloons. Reports were individually tabulated and events were categorized with special attention to AEs. METHODS: The FDA MAUDE database was queried for all medical device reports (MDR) related to nasal epistaxis balloon devices from January 2012 to November 2022. RESULTS: 19 MDRs met inclusion criteria. 5 MDRs were classified as device related (26.3 %); two events were reported for balloon leak and deflation, two events were reported for device breakage, and one device related event was unknown. 14 MDRs (73.7 %) were classified as patient related. Two documented MDRs were patient deaths due to exsanguination. Additional serious AEs included balloon ingestion and subsequent small bowel perforation (n = 1), cerebrospinal fluid leak (n = 1), skull base violation and intracranial placement of the device (n = 1), and respiratory distress (n = 3). CONCLUSION: Though epistaxis control with nasal balloons is generally seen as a safe procedure, there have been several concerning AEs reported. While two reports of death due to exsanguination were the most severe AEs, multiple other life-threatening AEs were also documented. Increased awareness of associated complications can be used to better counsel patients during the informed consent process as well as providers in their clinical decision making.

Color Change of Intranasal Fluorescein Cannot Detect Cerebrospinal Fluid Leaks.

BACKGROUND: The color change of topical intranasal fluorescein has been used to confirm the presence of cerebrospinal fluid (CSF) during endoscopic endonasal surgery. We aimed to validate the use of topical intranasal fluorescein for CSF detection. METHODS: Blood, CSF, saliva, and normal saline were combined with decreasing fluorescein concentrations (from 10% to 0.1%). The solutions were photographed in high definition on nasal pledgets and in 1.5-mL Eppendorf tubes. The color difference (ΔE) was objectively measured via the International Commission on Illumination coordinates. Four otolaryngologists who were unaware of the study parameters also evaluated the samples for perceptible color differences. The human eye cannot detect color differences at an International Commission on Illumination ΔE of <5. RESULTS: All otolaryngologists agreed a color difference could be seen with blood across all fluorescein concentrations. However, a perceptible color difference between the experimental samples that excluded blood was not appreciable. Objectively, the ΔE was <5 on average for all nonblood samples when mixed with 5% and 10% fluorescein in the Eppendorf experiment. The ΔE for the nonblood samples was >5 for the remaining tested. Similarly, the average ΔE for the nonblood samples in the pledget experiment was >5 across all fluorescein concentrations. The blood ΔE was consistently >50 throughout all fluorescein concentrations in the Eppendorf experiment and >20 throughout the pledget experiment, correlating with the subjective ease of discernment between blood and the control sample in both groups. CONCLUSIONS: Color change alone is not sufficient to determine a difference between CSF, saliva, and saline. Blood, however, is readily identified using this method. Adjunct characteristics, in addition to the color change, are necessary to properly identify an active CSF leak.

Economic implications of localization strategies for cerebrospinal fluid rhinorrhea.

BACKGROUND: The direct costs associated with different diagnostic algorithms to localize cerebrospinal fluid (CSF) rhinorrhea have not been described. METHODS: A decision-tree analysis of imaging modalities used to localize CSF rhinorrhea was performed to compare associated direct costs. The primary outcome was cost, which was determined based on reimbursement data published by the Centers for Medicare and Medicaid Services in 2018. The model was parameterized after a literature review of published studies was performed from 1990 to 2018 to estimate the sensitivity CSF rhinorrhea localization of the following radiographic modalities: high-resolution computed tomography (HRCT), magnetic resonance cisternography (MRC), and CT cisternography (CTC). In addition to base case analysis, 1-way sensitivity analyses were also performed to evaluate the robustness of results to changes in model parameters. RESULTS: Among patients with a high suspicion for CSF rhinorrhea, use of HRCT followed by exploration in the operating room if preliminary HRCT was negative was found to be the optimal localization modality from a cost perspective ($172.25). The next least costly algorithm was HRCT followed by MRC ($294.10). Imaging algorithms beginning with CTC were the next least costly modality ($727.37). Sensitivity analyses generally supported HRCT to be the optimal initial radiographic strategy over a wide range of parameter values. CONCLUSION: This work advocates HRCT as first-line modality to localize CSF rhinorrhea from a cost perspective. Although algorithms beginning with MRC were on average $35 more expensive than those starting with CTC, associated risks of CTC were not modeled and may play a role in decision making.

Sinonasal Disease in Total Laryngectomy Patients.

OBJECTIVE: Total laryngectomy (TL) results in complete abolition of nasal airflow, with notable pathologic alterations of the intranasal mucosa, mucociliary clearance, and nasal cycle. Despite these observed morphological changes, it remains unclear whether this subpopulation of patients experiences clinically significant sinonasal disease. The goal of this study was to identify rhinosinusitis in TL patients using radiographic imaging. METHODS: An Institutional Review Board-approved retrospective review (January 2005-July 2017) identified 50 patients who underwent radiographic imaging before and after TL. The Lund-Mackay Staging System (LM) was applied to 197 surveillance computed tomography scans. Surveyed patients also underwent investigation of current sinonasal symptomatology using the SNOT-22 questionnaire. Simple linear regression was modeled to LM scores; tests of statistical significance were estimated via the method of Kenward and Roger. RESULTS: The mean age was 62.4 years, with a 5:1 male-to-female ratio. The mean SNOT-22 score was 27.4 (range, 5-33). A median of 3 scans was obtained, 49% within 12 months after TL. The mean (± standard deviation) postoperative LM score was 2.7 ± 3.97 points (range, 0-19). For every 1 month after TL, postoperative LM was +0.01 point (P = .49). Conversely, for every +1 point in preoperative LM, postoperative LM was +1.08 points (P < .001). Two patients required functional endoscopic sinus surgery after TL for persistent sinonasal disease. CONCLUSIONS: Preoperative sinonasal disease burden likely plays an important role in the development of clinically significant rhinosinusitis in TL patients. Correlating radiographic findings to validated outcome measures remains a critical aspect of determining optimal surgical candidates; this arena is still under investigation in this unique patient cohort.

The versatility of the serratus anterior free flap in head and neck reconstruction.

OBJECTIVES/HYPOTHESIS: Review the literature on the use of the serratus anterior free flap in the head and neck reconstruction and describe new applications of the serratus anterior free flap. STUDY DESIGN: Case series with retrospective chart review and literature review. METHODS: A PubMed literature review was performed using the search terms "serratus free flap," "serratus skull base," "serratus scalp," and "serratus free tissue transfer." One hundred and seventy-six articles were identified, 22 of which included at least one head and neck reconstructive case utilizing the serratus free flap. Twenty-two articles were identified since 1982 that discussed the use of the serratus anterior free flap for reconstruction in the head and neck. However, most of these were harvested in conjunction with latissimus muscle. RESULTS: We present a case series of 15 patients in whom the serratus anterior muscle free flap was used alone for head and neck reconstruction. In seven of these patients, we used the serratus for coverage of the newly created pharynx after total laryngectomy, which has not previously been reported. CONCLUSION: The serratus anterior free muscle flap has great versatility in reconstruction of the head and neck. Because of its low donor site morbidity, thinness, and pliability, as well as its ease of harvest, it is ideal for reconstruction of the skull base and scalp. We have also found that it is ideal for muscle coverage of the newly reconstructed pharynx after total laryngectomy. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:568-573, 2017.

Peroxiredoxin-1 from the human hookworm Ancylostoma ceylanicum forms a stable oxidized decamer and is covalently inhibited by conoidin A.

Hookworms are parasitic nematodes that have a devastating impact on global health, particularly in developing countries. We report a biochemical and structural analysis of a peroxiredoxin from the hookworm Ancylostoma ceylanicum, AcePrx-1. Peroxiredoxins provide antioxidant protection and act as signaling molecules and chaperones. AcePrx-1 is expressed in adult hookworms and can be inactivated by 2,3-bis(bromomethyl)quinoxaline-1,4-dioxide (conoidin A). Conoidin A inactivates AcePrx-1 by alkylating or crosslinking the catalytic cysteines, while maintaining the enzyme in the "locally unfolded" conformation. Irreversible oxidation of the resolving cysteine may contribute additional inhibitory activity. A crystal structure of oxidized AcePrx-1 reveals a disulfide-linked decamer. A helix macrodipole near the active site increases the reactivity of the catalytic cysteines to conoidin A. This work demonstrates the promise of conoidin compounds as probes to evaluate peroxiredoxins as drug targets in human parasites.

Transgenic parasites stably expressing full-length Plasmodium falciparum circumsporozoite protein as a model for vaccine down-selection in mice using sterile protection as an endpoint.

Circumsporozoite protein (CSP) of Plasmodium falciparum is a protective human malaria vaccine candidate. There is an urgent need for models that can rapidly down-select novel CSP-based vaccine candidates. In the present study, the mouse-mosquito transmission cycle of a transgenic Plasmodium berghei malaria parasite stably expressing a functional full-length P. falciparum CSP was optimized to consistently produce infective sporozoites for protection studies. A minimal sporozoite challenge dose was established, and protection was defined as the absence of blood-stage parasites 14 days after intravenous challenge. The specificity of protection was confirmed by vaccinating mice with multiple CSP constructs of differing lengths and compositions. Constructs that induced high NANP repeat-specific antibody titers in enzyme-linked immunosorbent assays were protective, and the degree of protection was dependent on the antigen dose. There was a positive correlation between antibody avidity and protection. The antibodies in the protected mice recognized the native CSP on the parasites and showed sporozoite invasion inhibitory activity. Passive transfer of anti-CSP antibodies into naive mice also induced protection. Thus, we have demonstrated the utility of a mouse efficacy model to down-select human CSP-based vaccine formulations.

Alanine mutagenesis of the primary antigenic escape residue cluster, c1, of apical membrane antigen 1.

Antibodies against apical membrane antigen 1 (AMA1) inhibit invasion of Plasmodium merozoites into red cells, and a large number of single nucleotide polymorphisms on AMA1 allow the parasite to escape inhibitory antibodies. The availability of a crystal structure makes it possible to test protein engineering strategies to develop a monovalent broadly reactive vaccine. Previously, we showed that a linear stretch of polymorphic residues (amino acids 187 to 207), localized within the C1 cluster on domain 1, conferred the highest level of escape from inhibitory antibodies, and these were termed antigenic escape residues (AER). Here we test the hypothesis that immunodampening the C1 AER will divert the immune system toward more conserved regions. We substituted seven C1 AER of the FVO strain Plasmodium falciparum AMA1 with alanine residues (ALA). The resulting ALA protein was less immunogenic than the native protein in rabbits. Anti-ALA antibodies contained a higher proportion of cross-reactive domain 2 and domain 3 antibodies and had higher avidity than anti-FVO. No overall enhancement of cross-reactive inhibitory activity was observed when anti-FVO and anti-ALA sera were compared for their ability to inhibit invasion. Alanine mutations at the C1 AER had shifted the immune response toward cross-strain-reactive epitopes that were noninhibitory, refuting the hypothesis but confirming the importance of the C1 cluster as an inhibitory epitope. We further demonstrate that naturally occurring polymorphisms that fall within the C1 cluster can predict escape from cross-strain invasion inhibition, reinforcing the importance of the C1 cluster genotype for antigenic categorization and allelic shift analyses in future phase 2b trials.