The importance of the palatine bone for endoscopic endonasal skull base surgery.

Endoscopic endonasal skull base surgery is increasingly prevalent, with its scope expanding from pathogens in the midline region to those in the paramedian region. Maximizing anterior sphenoidectomy is important for the median approach, and lateralizing the pterygopalatine fossa is crucial for the paramedian approach. Maximizing the surgical corridor in the nasal cavity and minimizing damage to neurovascular structures are vital for establishing a surgical field with minimal bleeding, ensuring safe, precise, and gentle procedures. However, the relationship between the maxillofacial and skull base bones in endoscopic endonasal skull base surgery is difficult to understand because these bones are intricately articulated, making it challenging to visualize each bone's outline. Understanding important bones and their related neurovascular structures is essential for all skull base surgeons to maximize the surgical corridor and minimize iatrogenic injury to neurovascular structures. This study aimed to elucidate the role of the palatine bone from a microsurgical anatomical perspective. Three dry skulls were used to demonstrate the structure of the palatine bone and its relationship with surrounding bones. A formalin-perfused cadaveric head was dissected to show the related neurovascular structures. The arteries and veins of the cadaveric heads were injected with red- and blue-colored silicon. Dissection was performed using a surgical microscope and endoscope. In addition, the utilization of the palatine bone as a landmark to identify neurovascular structures, which aids in creating a wider surgical field with less bleeding, was shown in two representative cases. The palatine bone consists of unique complex structures, including the sphenoidal process, ethmoidal crest, pterygopalatine canal, and sphenopalatine notch, which are closely related to the sphenopalatine artery, maxillary nerve, and its branches. The ethmoidal crest of the palatine bone is a well-known structure that is useful for identifying the sphenopalatine foramen, controlling the sphenopalatine artery and nerve, and safely opening the pterygopalatine fossa. The sphenoidal process of the palatine bone is a valuable landmark for identifying the palatovaginal artery, which is a landmark used to safely and efficiently expose the vidian canal. The sphenoidal process is easily cracked with an osteotome and removed to expose the palatovaginal artery, which runs along the pharyngeal groove, just medial to the vidian canal. By opening the pterygopalatine canal (also known as the greater palatine canal), further lateralization of the periosteum-covered pterygopalatine fossa contents can be achieved. Overall, the sphenoidal process and ethmoidal crest can be used as important landmarks to maximize the surgical corridor and minimize unnecessary injury to neurovascular structures.

Survival outcomes including salvage therapy of adult head and neck para-meningeal rhabdomyosarcoma: a multicenter retrospective study from Japan.

BACKGROUND: Rhabdomyosarcoma is the most common soft tissue sarcoma in children, but rare in adults. Para-meningeal rhabdomyosarcoma in head and neck (PM-HNRMS) is less applicable for surgery due to the anatomic reason. PM-HNRMS has a poor prognosis in children. However, its clinical outcomes remain unclear in adults due to the rarity. Further, there is almost no detailed data about salvage therapy. METHODS: We retrospectively examined the adult patients with PM-HNRMS treated at institutions belonging to the Kyushu Medical Oncology Group from 2009 to 2022. We evaluated the overall survival (OS) and progression-free survival (PFS) of the patients who received a first-line therapy. We also reviewed the clinical outcomes of patients who progressed against a first-line therapy and received salvage therapy. RESULTS: Total 11 patients of PM-HNRMS received a first-line therapy. The characteristics were as follows: median age: 38 years (range 25 - 63 years), histology (alveolar/spindle): 10/1, and risk group (intermediate/high): 7/4. As a first-line therapy, VAC and ARST0431-based regimen was performed in 10 and 1 patients, respectively. During a first-line therapy, definitive radiation for all lesions were performed in seven patients. The median PFS was 14.2 months (95%CI: 6.0 - 25.8 months): 17.1 months (95%CI: 6.0 - not reached (NR)) for patients with stage I-III and 8.5 months (95%CI: 5.2 - 25.8 months) for patients with stage IV. The 1-year and 3-year PFS rates were 54.5% and 11.3% for all patients. Median OS in all patients was 40.8 months (95%CI: 12.1 months-NR): 40.8 months (95%CI: 12.1 - NR) for patients with stage I-III and NR for patients with stage IV. The 5-year OS rate was 48.5% for all patients. Among seven patients who received salvage therapy, three are still alive, two of whom remain disease-free for over 4 years after completion of the last therapy. Those two patients received multi-modal therapy including local therapy for all detected lesions. CONCLUSION: The cure rate of adult PM-HNRMS is low in spite of a first-line therapy in this study. Salvage therapy might prolong the survival in patients who received the multi-modal therapy including local therapy for all detected lesions.

An anatomical study of the sigmoid sinus artery: Application to the transmastoid approach.

INTRODUCTION: We aimed to investigate the morphological features of the artery that traverse the sigmoid sinus's lateral surface and to discuss this structure's clinical relevance. METHODS: Ten sides from five cadaveric Caucasian heads were used for gross anatomical dissection to investigate the morphological features of the sigmoid sinus artery (SSA), and additional five sides were used for histological observation. RESULTS: The SSA was found on eight out of ten sides (80%). The mean diameter of the SSA was 0.3 mm. The mean distance from the tip of the mastoid process to the artery was 20.3 mm. Histological observation identified extradural and intradural courses of SSA. The intradural course was further categorized into protruding and non-protruding types. In the protruding type, the SSA traveled within the dura but indented into the bone, making it more or less an intraosseous artery. In the non-protruding type, the SSA traveled within the dura but did not protrude into the bone but rather indented into the lumen of the SS. In all sections, both intradural and extradural courses were identified simultaneously. CONCLUSIONS: When the mastoid foramen is observed, it does not always only carry an emissary vein but also an artery. The SSA could be considered a "warning landmark" during bone drilling for the transmastoid approach.

Anatomy of small canals around the jugular foramen: Special reference to Jacobson's and Arnold's nerves.

The jugular foramen harbors anatomically complex bony, venous and neural structures. It is closely associated with small canals including the mastoid, tympanic, and cochlear canaliculi, and the stylomastoid foramen. The minute intraosseous branches of Arnold's and Jacobson's nerves (<1 mm in length) remain difficult to study with current imaging techniques, and cadaveric dissection is the most reliable approach. Our aim was to examine the variations of Jacobson's and Arnold's canaliculi and nerves and to provide detailed cadaveric graphics. To reveal the anatomical structures of small canals around the jugular foramen, 25 sides of dry skulls and 14 sides of cadaveric heads were examined. Intraosseous branches varied more in Arnold's nerve than Jacobson's nerve. In our cadaveric dissection, all specimens formed a single canal for Jacobson's nerve connecting the jugular foramen to the tympanic cavity. The intraosseous course of Arnold's nerve varied in its communication with the facial nerve. A descending branch crossing the facial nerve was identified in five of 14 sides, an ascending branch in 13. In two specimens, an ascending branch clearly reached the base of the stapedius muscle. Classical anatomical studies of cadavers remain a supplementary tool for analyzing these tiny structures. The present study confirms Gray's findings of 1913. Variations of these nerves could be even more complex than previously reported. Our study provides additional information regarding the anatomy of Jacobson's and Arnold's nerves.

Subtotal temporal bone resection en bloc with the parotid gland and temporomandibular joint: a 2-dimensional operative video.

Primary temporal bone squamous cell carcinoma is sporadic. According to previous studies, margin-negative resection provides the best prognosis (Nakagawa et al., 2006; Moody et al., 2000; Yin et al., 2006; Komune et al., 2021 [1-4]). When tumors extend behind the tympanic membrane, lateral temporal bone resection, which is a well-established procedure, is insufficient to achieve a tumor-free margin. For these cases, subtotal temporal bone resection (STBR) can achieve a complete en bloc resection with a tumor-free margin. Furthermore, STBR en bloc with surrounding structures, including the temporomandibular joint and parotid gland, complicates surgical techniques. We previously reported this surgical procedure in a stepwise manner using cadaveric dissection (Komune et al., 2014 [5]). The STBR en bloc with the parotid gland and temporomandibular joint is composed of three approaches according to our previous report: high cervical exposure (neck dissection), a subtemporal-infratemporal fossa approach, and a retromastoid-paracondylar approach. However, we currently lack demonstrative surgical videos. According to our previous report, this video first demonstrates STBR en bloc with the parotid gland and temporomandibular joint (Komune et al., 2014 [5]). The histopathological diagnosis of a 57-year-old woman suffering from a large tumor protruding from her auricle indicated squamous cell carcinoma; after the diagnosis she was referred to our hospital. Computed tomography revealed the full extent of the tumor, which was about 8 cm in diameter and had damaged the middle cranial base, mastoid bone, and middle ear cavity. Magnetic resonance imaging indicated invasion of the glenoid fossa and parotid gland, equivalent to a Pittsburg stage cT4 tumor. The patient underwent STBR en bloc with the parotid gland and temporomandibular joint. Lower cranial nerves (CN IX-XII) were preserved, and the patient achieved normal oral intake without additional procedures after surgery. At six months post-operation, no recurrence was noted. In this video, we first demonstrate the surgical procedure of the STBR en bloc with the parotid gland and temporomandibular joint for far-advanced temporal bone squamous cell carcinoma, and it can be one of the surgical options to achieve the complete resection without exposure of the tumor. Informed consent was obtained from the patient. The video was reproduced with the written informed consent of the patient. Primary temporal bone squamous cell carcinoma is sporadic. According to previous studies, margin-negative resection provides the best prognosis (Nakagawa et al., 2006; Moody et al., 2000; Yin et al., 2006; Komune et al., 2021 [1-4]). When tumors extend behind the tympanic membrane, lateral temporal bone resection, which is a well-established procedure, is insufficient to achieve a tumor-free margin. For these cases, subtotal temporal bone resection (STBR) can achieve a complete en bloc resection with a tumor-free margin. Furthermore, STBR en bloc with surrounding structures, including the temporomandibular joint and parotid gland, complicates surgical techniques. We previously reported this surgical procedure in a stepwise manner using cadaveric dissection (Komune et al., 2014 [5]). The STBR en bloc with the parotid gland and temporomandibular joint is composed of three approaches according to our previous report: high cervical exposure (neck dissection), a subtemporal-infratemporal fossa approach, and a retromastoid-paracondylar approach. However, we currently lack demonstrative surgical videos. According to our previous report, this video first demonstrates STBR en bloc with the parotid gland and temporomandibular joint (Komune et al., 2014 [5]). The histopathological diagnosis of a 57-year-old woman suffering from a large tumor protruding from her auricle indicated squamous cell carcinoma; after the diagnosis she was referred to our hospital. Computed tomography revealed the full extent of the tumor, which was about 8 cm in diameter and had damaged the middle cranial base, mastoid bone, and middle ear cavity. Magnetic resonance imaging indicated invasion of the glenoid fossa and parotid gland, equivalent to a Pittsburg stage cT4 tumor. The patient underwent STBR en bloc with the parotid gland and temporomandibular joint. Lower cranial nerves (CN IX-XII) were preserved, and the patient achieved normal oral intake without additional procedures after surgery. At six months post-operation, no recurrence was noted. In this video, we first demonstrate the surgical procedure of the STBR en bloc with the parotid gland and temporomandibular joint for far-advanced temporal bone squamous cell carcinoma, and it can be one of the surgical options to achieve the complete resection without exposure of the tumor. Informed consent was obtained from the patient. The video was reproduced with the written informed consent of the patient.

Genetic landscape of external auditory canal squamous cell carcinoma.

External auditory canal squamous cell carcinoma (EACSCC) is an extremely rare and aggressive malignancy. Due to its rarity, the molecular and genetic characteristics of EACSCC have not yet been elucidated. To reveal the genetic alterations of EACSCC, we performed whole exome sequencing (WES) on 11 primary tumors, 1 relapsed tumor and 10 noncancerous tissues from 10 patients with EACSCC, including 1 with a rare case of synchronous bilateral EACSCC of both ears. WES of the primary tumor samples showed that the most frequently mutated gene is TP53 (63.6%). In addition, recurrent mutations in CDKN2A, NOTCH1, NOTCH2, FAT1 and FAT3 were detected in multiple samples. The mutational signature analysis of primary tumors indicated that the mutational processes associated with the activation of apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) deaminases are the most common in EACSCC, suggesting its similarity to SCC from other primary sites. Analysis of arm-level copy number alterations detected notable amplification of chromosomes 3q, 5p and 8q as well as deletion of 3p across multiple samples. Focal chromosomal aberrations included amplifications of 5p15.33 (ZDHHC11B) and 7p14.1 (TARP) as well as deletion of 9p21.3 (CDKN2A/B). The protein expression levels of ZDHHC11B and TARP in EACSCC tissues were validated by immunohistochemistry. Moreover, WES of the primary and relapsed tumors from a case of synchronous bilateral EACSCC showed the intrapatient genetic heterogeneity of EACSCC. In summary, this study provides the first evidence for genetic alterations of EACSCC. Our findings suggest that EACSCC mostly resembles other SCC.

Use of negative pressure wound therapy to treat a cochlear implant infection around the auricle: a case report.

Although negative pressure wound therapy (NPWT) is widely used, its application to the head and neck region remains challenging due to anatomical complexities. This report presents the case of a female patient presenting with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes, uncontrolled diabetes and severe bilateral sensorineural hearing loss. The patient had undergone cochlear implant surgery and five months later the wound was infected with methicillin-resistant Staphylococcus aureus (MRSA). NPWT was started shortly after removing the internal receiver and was stopped 11 days later. NPWT helped in controlling infection and led to a successful wound closure. In this case, NPWT was effective in treating infectious wounds around the auricle after cochlear implant surgery. Declaration of interest: The authors have no financial support for this article and no conflict of interest directly relevant to the content of this article.

Recent advances in Otology: Current landscape and future direction.

Hearing is an essential sensation, and its deterioration leads to a significant decrease in the quality of life. Thus, great efforts have been made by otologists to preserve and recover hearing. Our knowledge regarding the field of otology has progressed with advances in technology, and otologists have sought to develop novel approaches in the field of otologic surgery to achieve higher hearing recovery or preservation rates. This requires knowledge regarding the anatomy of the temporal bone and the physiology of hearing. Basic research in the field of otology has progressed with advances in molecular biology and genetics. This review summarizes the current views and recent advances in the field of otology and otologic surgery, especially from the viewpoint of young Japanese clinician-scientists, and presents the perspectives and future directions for several topics in the field of otology. This review will aid next-generation researchers in understanding the recent advances and future challenges in the field of otology.

Endoscopic Management of a Case of Spontaneous Cerebrospinal Fluid Leaks in Anterior Skull Base.

Spontaneous cerebrospinal fluid (sCSF) leaks are rare, and their diagnosis and treatment often present significant challenges. This paper discusses and reports cases experienced at our facility. We retrospectively reviewed three of five cases of sCSF leaks experienced at the Department of Otolaryngology and Head and Neck Surgery, Kyushu University, from December 2020 to December 2022, excluding CSF otorrhea. All three patients were female; their mean age was 56 years (44-71 years). Two of the three patients were obese (first degree), and one was average weight (according to the criteria of the Japan Society for the Study of Obesity). Two patients had hypertension, and one had sleep apnea syndrome as an underlying disease. In all cases, leakage sites, which were all the cribriform plate, can be endoscopically identified, and all could be closed by an endoscopic intranasal approach. We reviewed cases of sCSF leaks. Although some patients had difficulty identifying the leakage site in a narrow and complex nasal cavity, an endoscopic survey was useful in identifying the leakage site. All cases were closed and there were no signs of recurrence. Identifying the site of leakage and selecting the appropriate closure method depending on the extent of the leakage is essential in treating such cases.

Clinical, anatomical, and histological features of the rhomboid lip and considerations for surgery using a retrosigmoid approach: a retrospective study.

OBJECTIVE: The rhomboid lip is a neural tissue encountered during cerebellopontine angle surgery, with differing shape and extent among individuals. This study aimed to investigate the variation of rhomboid lips during posterior fossa surgery. METHODS: In this retrospective study, we examined posterior cranial fossa surgeries performed using a retrosigmoid approach. Rhomboid lips were classified according to thickness, extent, and appearance, with some subjected to histological analysis. T2-weighted magnetic resonance imaging (MRI) of rhomboid lips was conducted. RESULTS: Among 304 surgeries, rhomboid lips were observed in 75 patients who underwent schwannoma or meningioma resection, facial spasm-related neurovascular decompression, and other surgeries (37, 2, 32, and 4 patients, respectively). Rhomboid lips were categorized based on apparent thickness: thin membranous type, resembling an arachnoid membrane, and thick parenchymal type. Rhomboid lip extension was classified by position relative to the choroid plexus: non-extension, lateral extension, and jugular foramen (41, 22, and 12 patients, respectively). Veins were observed on the rhomboid lip surface in 37 cases. The rhomboid lip was visible in only one case (parenchymal jugular foramen type) on MRI. Histologically, the rhomboid lip comprised an ependymal cell layer, a glial layer, and connecting tissue. The glial layer thickness determined the rhomboid lip thickness, which was greater in the parenchymal type than in the membrane type. In 42 patients, the rhomboid lip was dissected, with no complications observed. CONCLUSIONS: Morphological classification of the rhomboid lip and understanding of its anatomical details contribute to safe surgical field development for neurosurgeons.

Inhibition of PTPN3 Expressed in Activated Lymphocytes Enhances the Antitumor Effects of Anti-PD-1 Therapy in Head and Neck Cancer, Especially in Hypoxic Environments.

In the tumor microenvironment, wherein cytotoxic lymphocytes interact with cancer cells, lymphocyte exhaustion, an immune checkpoint inhibitor target, is promoted. However, the efficacy of these inhibitors is limited, and improving response rates remains challenging. We previously reported that protein tyrosine phosphatase nonreceptor type (PTPN) 3 is a potential immune checkpoint molecule for activated lymphocytes and that PTPN3 inhibition should be a focus area for cancer immunotherapy development. Therefore, in this study, we focused on PTPN3-suppressive therapy in terms of lymphocyte exhaustion under hypoxic conditions, which are a cancer microenvironment, and investigated measures for improving the response to anti-programmed death receptor (PD)-1 antibody drugs. We found that PTPN3 expression was upregulated in activated lymphocytes under hypoxic conditions, similar to the findings for other immune checkpoint molecules, such as PD-1, T cell immunoglobulin mucin-3, and lymphocyte-activation gene-3; furthermore, it functioned as a lymphocyte exhaustion marker. In addition, PTPN3-suppressed activated lymphocytes promoted the mammalian target of rapamycin (mTOR)-Akt signaling pathway activation and enhanced proliferation, migration, and cytotoxic activities under hypoxic conditions. Furthermore, PTPN3 suppression in activated lymphocytes increased PD-1 expression and enhanced the antitumor effects of anti-PD-1 antibody drugs against head and neck cancer in vitro and in vivo. These results suggest that the suppression of PTPN3 expression in activated lymphocytes enhances the therapeutic effect of anti-PD-1 antibody drugs in head and neck cancer, especially under hypoxic conditions that cause lymphocyte exhaustion.

Correction: Effectiveness and safety of weekly paclitaxel and cetuximab as a salvage chemotherapy following immune checkpoint inhibitors for recurrent or metastatic head and neck squamous cell carcinoma: a multicenter clinical study.

[This corrects the article DOI: 10.1371/journal.pone.0271907.].

Takedown and Reuse of a Posterior Septal Nasal Floor Mucosal Flap for Skull Base Reconstruction in a Revision Surgery for a Recurrent Pituitary Tumor.

Various types of mucosal flaps can be used for skull base reconstruction after endoscopic endonasal skull base surgery (EESS). Preventing postoperative cerebrospinal fluid (CSF) leakage is essential. Flap creation during revision surgery can be problematic. We present a patient in whom a posterior septal nasal floor flap (PS-NF) was successfully reused for reconstruction after multiple reoperations for pituitary tumor resection. A 22-year-old female underwent EESS for resection of a pituitary tumor and experienced multiple recurrences after repeated operations. For the third recurrence, a skull base surgery team comprising otolaryngologists and neurosurgeons performed a binostril combined transnasal/transseptal approach and used a PS-NF for reconstruction. For the fourth recurrence, a PS-NF was successfully taken down and reused for reconstruction. No postoperative CSF leakage or intranasal complications occurred. Skull base reconstruction using a PS-NF is feasible and preserves the mucous membrane of the nasal septum and the morphology of the nasal cavity. PS-NF takedown and reuse is an option for revision EESS for recurrent pituitary tumors.

Impact of Positive-Margin Resection of External Auditory Canal Squamous Cell Carcinoma.

BACKGROUND: Positive-margin resection of external auditory canal squamous cell carcinoma (EAC-SCC) is still a major cause of recurrence. The aim of this study is to examine the clinical impact of positive-margin resection of EAC-SCCs. METHODS: We retrospectively reviewed 40 surgical cases with en bloc temporal bone resection of EAC-SCC at a tertiary referral center from October 2016 to March 2022. RESULTS: Two-year disease-specific, overall, and disease-free survival rates for all 40 cases reviewed were 85.2%, 88.85%, and 76.96%, respectively. En bloc resection with a negative margin significantly improved patient prognosis (p < 0.001). Positive-margin resection was observed in 9/40 cases (22.5%). Insufficient assessment of preoperative images was the cause in two of these cases. Postoperative lymph node metastasis and distant metastasis were observed in cases in which vascular, lymphatic duct or perineural invasion was found on postoperative pathological examination. In addition, three cases in which no vascular, lymphatic duct, or perineural invasion was found exhibited local recurrence during the follow-up period. Of the nine positive-margin resection cases, only two showed no postoperative recurrence. CONCLUSIONS: Once positive-margin resections are confirmed, cases might have a high risk of tumor recurrence, even with the addition of postoperative adjuvant chemoradiotherapy.

High-risk HPV-related squamous cell carcinoma in the temporal bone: a rare but noteworthy subtype.

High-risk human papillomavirus (HPV) is a risk factor for the development of several head and neck squamous cell carcinomas (SCCs). However, there have been few reports of high-risk HPV infection in temporal bone squamous cell carcinomas (TBSCCs), and thus the prevalence and clinicopathologic significance of high-risk HPV in TBSCCs are still unclear. We retrospectively collected 131 TBSCCs and analyzed them for transcriptionally active high-risk HPV infection using messenger RNA in situ hybridization; we also assessed the utility of p16-immunohistochemistry (IHC) and Rb-IHC to predict HPV infection. Eighteen (13.7%) of the 131 TBSCCs were positive for p16-IHC, and five of them were positive for high-risk HPV infection (the estimated high-risk HPV positivity rate was 3.8% [5/131]). Interestingly, all five HPV-positive patients were male and had TBSCC on the right side. In the p16-IHC+/HPV+ cases (n = 5), the Rb-IHC showed a partial loss pattern (n = 4) or complete loss pattern (n = 1). In contrast, all p16-IHC-negative cases (n = 113) showed an Rb-IHC preserved pattern. The positive predictive value (PPV) of p16-IHC positivity for high-risk HPV infection was low at 27.8%, while the combination of p16-IHC+/Rb-IHC partial loss pattern showed excellent reliability with a PPV of 100%. The prognostic significance of high-risk HPV infection remained unclear. High-risk HPV-related TBSCC is an extremely rare but noteworthy subtype.

Biological and genetic characterization of a newly established human external auditory canal carcinoma cell line, SCEACono2.

Squamous cell carcinoma of the external auditory canal (EACSCC) is an extraordinarily rare and aggressive malignant disease. Establishment of EACSCC cell line with robust molecular characteristics is essential for the basic and translational research of EACSCC. Here, we show the newly established EACSCC cell line SCEACono2, derived from a patient with well-to-moderately differentiated EACSCC. We analyzed histologic and genetic features of SCEACono2 hiring multiple experiments, including next-generation sequencing (NGS). Immunocytochemical staining of SCEACono2 showed positivity of p53 and SCC1/2. Furthermore, SCEACono2 exhibited a unique characteristic that cytokeratin, vimentin as well as cancer stem cell markers (CD44, CD133, ALP and Oct3/4) were positive. SCEACono2 had an ability to form tumors at the temporal lesion xenograft nude mice model. NGS revealed that SCEACono2 harbored the somatic mutations of TP53 (p.G245S) and NOTCH1 (p.A465T). RNA-seq and downstream bioinformatics analysis revealed significant enrichment of genes involved in inflammation and cell adhesion in SCEACono2 compared to SCC-9 and HSC-4. STR profiling indicated no evidence of cross-contamination. In conclusion, SCEACono2 could serves as a promising and robust research resource of EACSCC in vitro and in vivo.

No evidence for an association between persistent measles virus infection and otosclerosis among patients with otosclerosis in Japan.

Otosclerosis, which is characterized by disordered bone remodeling, occurs exclusively in the human temporal bone. The etiology of the disease is unknown, but a popular hypothesis is that it is caused by persistent measles virus (MV) infection. Paramyxovirus-like filamentous structures were found in otosclerotic lesions of stapes footplates from patients with otosclerosis. Although MV RNAs have been detected in otosclerotic samples by using reverse transcription-PCR, no complete MV mRNA sequence has been reported, nor has infectious virus been isolated from clinical samples. Furthermore, one study failed to obtain evidence of MV infection in otosclerotic bone samples. In this study, we tested, by three different protocols, for the presence of MV in clinical samples from patients with otosclerosis in Japan. We used a highly sensitive reverse transcription-quantitative PCR method which is able to detect viral mRNA in cells infected with MV at around one infectious unit per well. We obtained no evidence of MV infection in bone samples, primary cell cultures derived from stapes bones, or MV-susceptible cell lines (Vero/hSLAM and II-18 cells) cocultured with bone samples or primary cell cultures derived from them. Thus, our results do not support the hypothesis that persistent MV infection is involved in the pathoetiology of otosclerosis.

Measles virus V protein inhibits NLRP3 inflammasome-mediated interleukin-1ß secretion.

Inflammasomes are cytosolic protein complexes that stimulate the activation of caspase-1, which in turn induces the secretion of the inflammatory cytokines Interleukin-1ß (IL-1ß) and IL-18. Recent studies have indicated that the inflammasome known as the NOD-like-receptor-family, pyrin domain-containing 3 (NLRP3) inflammasome recognizes several RNA viruses, including the influenza and encephalomyocarditis viruses, whereas the retinoic acid-inducible gene I (RIG-I) inflammasome may detect vesicular stomatitis virus. We demonstrate that measles virus (MV) infection induces caspase-1-dependent IL-1ß secretion in the human macrophage-like cell line THP-1. Gene knockdown experiments indicated that IL-1ß secretion in MV-infected THP-1 cells was mediated by the NLRP3 inflammasome but not the RIG-I inflammasome. MV produces the nonstructural V protein, which has been shown to antagonize host innate immune responses. The recombinant MV lacking the V protein induced more IL-1ß than the parental virus. THP-1 cells stably expressing the V protein suppressed NLRP3 inflammasome-mediated IL-1ß secretion. Furthermore, coimmunoprecipitation assays revealed that the V protein interacts with NLRP3 through its carboxyl-terminal domain. NLRP3 was located in cytoplasmic granular structures in THP-1 cells stably expressing the V protein, but upon inflammasome activation, NLRP3 was redistributed to the perinuclear region, where it colocalized with the V protein. These results indicate that the V protein of MV suppresses NLRP3 inflammasome-mediated IL-1ß secretion by directly or indirectly interacting with NLRP3.

Orientation of the Cochlea From a Surgeon's Perspective.

Background: One of the mechanisms that cause tip fold-over is a misalignment between the electrode array's coiling direction and the cochlea's curving direction. Objectives: We reviewed surgical videos and computed tomography (CT) datasets of the patients who underwent cochlear implantation procedures from January 2010 to December 2021, paying particular attention to the cochlea's orientation in the surgeon's microscopic view. Methods: CT dataset and video recordings were analyzed to measure the "slope angle," which is the angle between the cochlea's coiling plane and the horizontal plane. Results: There were 220 cases that met the criteria and completed the analysis. The mean slope angle was 12.1° ± 9.5°, with a minimum of -9.4° and maximum of 44.6°. However, each surgeon had a favored slope angle range. Conclusion: Understanding the slope angle and making an effort to reduce the chance of misalignment during electrode insertion may help prevent tip fold-over of slim perimodiolar electrode arrays.