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Loss of function of the neurofibromatosis type 2 (NF2) tumor suppressor gene leads to the formation of schwannomas, meningiomas, and ependymomas, comprising ∼50% of all sporadic cases of primary nervous system tumors. NF2 syndrome is an autosomal dominant condition, with bi-allelic inactivation of germline and somatic alleles resulting in loss of function of the encoded protein merlin and activation of mammalian target of rapamycin (mTOR) pathway signaling in NF2-deficient cells. Here we describe a gene replacement approach through direct intratumoral injection of an adeno-associated virus vector expressing merlin in a novel human schwannoma model in nude mice. In culture, the introduction of an AAV1 vector encoding merlin into CRISPR-modified human NF2-null arachnoidal cells (ACs) or Schwann cells (SCs) was associated with decreased size and mTORC1 pathway activation consistent with restored merlin activity. In vivo, a single injection of AAV1-merlin directly into human NF2-null SC-derived tumors growing in the sciatic nerve of nude mice led to regression of tumors over a 10-week period, associated with a decrease in dividing cells and an increase in apoptosis, in comparison with vehicle. These studies establish that merlin re-expression via gene replacement in NF2-null schwannomas is sufficient to cause tumor regression, thereby potentially providing an effective treatment for NF2.

Objectives: This study compared the immune‐related secretory capacity of human vestibular schwannoma (VS) and tumor‐assisted macrophages (TAMs) with their normal counterparts (Schwann cells [SC] and peripheral blood monocyte‐derived macrophages [Mo‐MFs], respectively), and examined relationships with presurgical hearing and tumor size. Methods: VS tumors (n = 16), auditory nerve (n = 1), blood (n = 9), and great auricular nerves (n = 3) were used. SCs (S100B+) and TAMs (CD68+) were isolated from VS tissue for culture. The secreted levels of 65 immune‐related factors were measured and compared using unpaired t‐tests with Welch correction (schwannoma vs. SCs) or Mann–Whitney tests (TAMs and Mo‐MFs). Associations between factor concentration and word recognition (WR), pure‐tone average (PTA), and tumor size were evaluated with Spearman correlation. Results: Secreted factors with significantly higher concentrations in schwannoma versus SC supernatants included IL‐2 and BAFF, whereas MMP‐1, IL‐6, FGF‐2, VEGF‐A, MIP‐3α, and GRO‐α concentrations were significantly higher in TAMs versus Mo‐MFs (all p < 0.05). Worse WR was significantly associated with higher secretion of fractalkine, eotaxin‐3, CD30, and IL‐16 by VS cells; IP‐10, eotaxin‐3, multiple interleukins, GM‐CSF, SCF, and CD30 by TAMs; and TNF‐α and MIP‐1α by Mo‐MFs (all p < 0.05). Worse PTA was significantly correlated with higher secretion of IL‐16 by VS cells (p < 0.05). Larger tumor size was significantly correlated with higher secretion of eotaxin by VS cells, and of IL‐7, IL‐21, and LIF by TAMs (all p = 0.017). Conclusions: Differential secretion of immune‐related factors was observed in schwannoma versus normal SCs and in TAMs versus Mo‐MFs, some of which were correlated with worse hearing and larger VS tumors. Level of Evidence: N/A Laryngoscope, 134:S1–S14, 2024 [ABSTRACT FROM AUTHOR]

Objective: To determine how augmented reality (AR) has been applied to the field of otology/neurotology, examine trends and gaps in research, and provide an assessment of the future potential of this technology within surgical practice and education. Data Sources: PubMed, EMBASE, and Cochrane Library were assessed from their inceptions through October 2022. A manual bibliography search was also conducted. Review Methods: A scoping review was conducted and reported according to PRISMA‐ScR guidelines. Data from studies describing the application of AR to the field of otology/neurotology were evaluated, according to a priori inclusion/exclusion criteria. Exclusion criteria included non‐English language articles, abstracts, letters/commentaries, conference papers, and review articles. Results: Eighteen articles covering a diverse range of AR platforms were included. Publication dates spanned from 2007 to 2022 and the rate of publication increased over this time. Six of 18 studies were case series in human patients although the remaining were proof of concepts in cadaveric/artificial/animal models. The most common application of AR was for surgical navigation (14 of 18 studies). Computed tomography was the most common source of input data. Few studies noted potential applications to surgical training. Conclusion: Interest in the application of AR to otology/neurotology is growing based on the number of recent publications that use a broad range of hardware, software, and AR platforms. Large gaps in research such as the need for submillimeter registration error must be addressed prior to adoption in the operating room and for educational purposes. Level of Evidence: N/A Laryngoscope, 133:1786–1795, 2023 [ABSTRACT FROM AUTHOR]

Observations of interhemispheric asymmetry in the cusp region due to the interplanetary magnetic field (IMF) By component have been performed for years, but those observations typically are not simultaneous in both hemispheres and represent an average picture. Simultaneous instantaneous observations in both hemispheres are rare. We have combined four sets of magnetometers in Antarctica to produce equivalent ionospheric currents and current amplitudes at 10 s resolution using the spherical elementary current systems technique. These Antarctica spherical elementary currents are roughly conjugate to the northern hemisphere spherical elementary currents derived over Greenland and North America. We examined five intervals with large interplanetary magnetic field By positive and negative and demonstrate that the equivalent current pattern in opposite hemispheres are asymmetric with respect to one another during IMF By positive with the cusp throat opening towards the dusk in the northern hemisphere and towards the dawn in the southern hemisphere. This configuration reverses for interplanetary magnetic field By negative. In one of these events we examine the rotation of the equivalent currents in real time in the northern hemisphere. We also compare these results with virtual magnetometer predictions from the Space Weather Modeling Framework. Simultaneous spherical elementary currents observations in both hemispheres are important because they allow us to observe the evolution of the cusp throat during changing solar wind and interplanetary magnetic field conditions. Key Points: We show the instantaneous equivalent ionospheric current orientation in the cusp for positive and negative IMF ByWe demonstrate that this pattern is reversed in opposite hemispheresMagnetically conjugate spherical elementary currents provide an opportunity to observe the high temporal variation in the cusp region [ABSTRACT FROM AUTHOR]