Modified procedure for reconstructing the inferomedial orbital wall: silicone sheet implantation without surgical removal.

BACKGROUND: Due to the complexity of reconstructing wide inferomedial orbital wall fractures, silicone sheets are the preferred choice of reconstructive material. Nevertheless, it is crucial to remove the silicone sheet postoperatively due to the risk of delayed complications associated with its placement. METHODS: We developed a procedure in which a silicone sheet implanted in the orbit can be extracted through the nasal cavity by removing the fractured portion of the medial orbital wall. CONCLUSION: This procedure enables the utilization of silicone sheets, which are suitable for intricate orbital reconstruction, without any concerns regarding delayed complications.

An innovative reconstruction procedure for fractures extending to the posterior orbital floor: utilizing the inferior margin of the greater wing of the sphenoid bone for reconstruction.

PURPOSE: No definitive procedures have been proposed for orbital floor fractures extending to the slope of the posterior end, which is a challenging problem. This study demonstrates the effectiveness of an orbital reconstruction procedure based on anatomical landmarks that we developed, called the three landmarks procedure (TLP). METHODS: This study is a single-center retrospective cohort study conducted by the Department of Otorhinolaryngology, Japanese Red Cross Asahikawa Hospital. Data were collected from April 2000 to December 2023. The effect of TLP and the balloon procedure (BP) on ocular movement was compared. The prevalence of postoperative enophthalmos after TLP was examined. RESULTS: The study included 17 patients who underwent TLP and 25 patients who underwent BP. Postoperative mean Hess area ratio (HAR%) was 98.3 (95% confidence interval (CI), 97.0-99.6) in the TLP group and 88.6 (95% CI 83.2-94.0) in the BP group. Among study patients with fractures extending to the posterior slope, 14 underwent TLP and 16 underwent BP. Postoperative mean HAR% was 98.5 (95% CI 97.3-99.7) in the TLP group and 89.2 (95% CI 82.4-95.8) in the BP group. Among all patients who underwent TLP, mean postoperative enophthalmos was 0.06 mm (95% CI - 0.32 to 0.44). It was 0.14 mm (95% CI - 0.31 to 0.59) among patients with fractures extending to the posterior slope. CONCLUSION: TLP resulted in better postoperative ocular movements than BP. Furthermore, TLP is an effective technique for treating fractures extending to the posterior slope, which are challenging to reconstruct.

S100A8 enhances IL-1ß production from nasal epithelial cells in eosinophilic chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis is classified into eosinophilic chronic rhinosinusitis (ECRS) and non-eosinophilic chronic rhinosinusitis (NECRS). ECRS is a refractory allergic disease involving a variety of immune and epithelial cells. S100A8 is a damage-associated molecular pattern that is closely related to allergic inflammation. However, the pathological implications of S100A8 in ECRS have not been clarified. METHODS: We evaluated the role of S100A8 in the pathogenesis of ECRS. Gene expression profiles of nasal polyps obtained from patients with ECRS or NECRS were evaluated using RNA sequencing. RESULTS: S100A8 was identified as a significantly upregulated gene in nasal polyps associated with ECRS. Immunohistochemistry consistently revealed intense S100A8 staining in nasal polyps from patients with ECRS. Human nasal epithelial cells expressed the receptor for advanced glycation end products and Toll-like receptor 4. Recombinant S100A8 protein induced interleukin-1ß secretion in human nasal epithelial cells. CONCLUSIONS: Our data demonstrate that S100A8 results in production of interleukin-1ß in the nasal epithelium, which may be involved in the pathogenesis of ECRS.

Accuracy of Therapeutic Drug Monitoring of Teicoplanin at the Onset of Febrile Neutropenia.

Background and Objectives: Teicoplanin (TEIC) is an effective drug for patients with febrile neutropenia (FN); however, it has been reported that these patients may have increased TEIC clearance compared with patients who do not have FN. The purpose of this study was to study therapeutic drug monitoring in patients with FN when the TEIC dosing design was based on the population mean method. Materials and Methods: Thirty-nine FN patients with hematological malignancy were included in the study. To calculate the predicted blood concentration of TEIC, we used the two population pharmacokinetic (population PK) parameters (parameters 1 and 2) reported by Nakayama et al. and parameter 3, which is a modification of the population PK of Nakayama et al. We calculated the mean prediction error (ME), an indicator of prediction bias, and the mean absolute prediction error (MAE), an indicator of accuracy. Furthermore, the percentage of predicted TEIC blood concentration within 25% and 50% of the measured TEIC blood concentration was calculated. Results: The ME values were -0.54, -0.25, and -0.30 and the MAE values were 2.29, 2.19, and 2.22 for parameters 1, 2, and 3, respectively. For all of the three parameters, the ME values were calculated as minus values, and the predicted concentrations tended to be biased toward smaller values relative to the measured concentrations. Patients with serum creatinine (Scr) < 0.6 mg/dL and neutrophil counts < 100/µL had greater ME and MAE values and a smaller percentage of predicted TEIC blood concentration within 25% of measured TEIC blood concentrations compared with other patients. Conclusions: In patients with FN, the accuracy of predicting TEIC blood concentrations was good, with no significant differences between each parameter. However, patients with a Scr < 0.6 mg/dL and a neutrophil count < 100/µL showed slightly inferior prediction accuracy.

Modified procedure for reconstructing the inferior wall of the orbit: identification of a reliable new landmark.

BACKGROUND: In orbital floor reconstruction, fractures involving the slope of the posterior end of the orbital floor make it difficult to determine the best location for implant placement. Therefore, landmarks for reconstruction are desirable to perform safe and reproducible reconstruction surgery. METHODS: We developed a surgical procedure that focuses on three orbital landmarks: the infraorbital nerve, the inferior margin of the greater wing of the sphenoid bone, and the posterior superior wall of the maxilla. CONCLUSIONS: Landmark-based orbital floor fracture reconstruction enables accurate reconstruction of fractures that extend to the slope of the posterior end of the orbital floor.

Pathological and therapeutic implications of eosinophil-derived semaphorin 4D in eosinophilic chronic rhinosinusitis.

BACKGROUND: Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis. Clinical markers for ECRS disease activity and treatment strategies have not been sufficiently established. Although semaphorins are originally identified as neuronal guidance factors, it is becoming clear that they play key roles in immune regulation and inflammatory diseases. OBJECTIVE: We sought to investigate the pathological functions and therapeutic potential of semaphorin 4D (SEMA4D) in ECRS. METHODS: Serum soluble SEMA4D levels in patients with paranasal sinus diseases were measured by ELISA. The expression of SEMA4D in blood cells and nasal polyp tissues was assessed by flow cytometry and immunohistochemistry, respectively. Generation of soluble SEMA4D was evaluated in matrix metalloproteinase-treated eosinophils. Endothelial cells were stimulated with recombinant SEMA4D, followed by eosinophil transendothelial migration assays. Allergic chronic rhinosinusitis was induced in mice using Aspergillus protease with ovalbumin. The efficacy of treatment with anti-SEMA4D antibody was evaluated histologically and by nasal lavage fluid analysis. RESULTS: Serum soluble SEMA4D levels were elevated in patients with ECRS and positively correlated with disease severity. Tissue-infiltrated eosinophils in nasal polyps from patients with ECRS stained strongly with anti-SEMA4D antibody. Cell surface expression of SEMA4D on eosinophils from patients with ECRS was reduced, which was due to matrix metalloproteinase-9-mediated cleavage of membrane SEMA4D. Soluble SEMA4D induced eosinophil transendothelial migration. Treatment with anti-SEMA4D antibody ameliorated eosinophilic infiltration in sinus tissues and nasal lavage fluid in the ECRS animal model. CONCLUSIONS: Eosinophil-derived SEMA4D aggravates ECRS. Levels of serum SEMA4D reflect disease severity, and anti-SEMA4D antibody has therapeutic potential as a treatment for ECRS.

Eosinophil-derived neurotoxin enhances airway remodeling in eosinophilic chronic rhinosinusitis and correlates with disease severity.

Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis (CRS) that is characterized by intractable nasal polyp formation. Eosinophil-derived neurotoxin (EDN) is an eosinophil granule protein that is closely related to allergic inflammation, but the pathological implications of EDN in ECRS remain unknown. In this study, we evaluated the function of EDN in ECRS pathogenesis and assessed its potential as a disease activity marker. Serum EDN levels were significantly higher in patients with ECRS than in those with other nasal and paranasal diseases, and were positively correlated with clinical disease activity. Production of EDN from isolated human eosinophils was induced by stimulation with IL-5 in vitro. Human nasal epithelial cells were stimulated with EDN, and the resultant changes in gene expression were detected by RNA sequencing. Pathway analysis revealed that the major canonical pathway affected by EDN stimulation was 'regulation of the epithelial-mesenchymal transition pathway'; the only gene in this pathway to be up-regulated was matrix metalloproteinase 9 (MMP-9). Consistent with this, immunostaining analysis revealed intense staining of both EDN and MMP-9 in nasal polyps from patients with ECRS. In conclusion, our data demonstrate that serum EDN level is a useful marker for the evaluation of ECRS severity. Furthermore, EDN induces production of MMP-9 from the nasal epithelium, which may be involved in the pathogenesis of ECRS.

Lysosomal Protein Lamtor1 Controls Innate Immune Responses via Nuclear Translocation of Transcription Factor EB.

Amino acid metabolism plays important roles in innate immune cells, including macrophages. Recently, we reported that a lysosomal adaptor protein, Lamtor1, which serves as the scaffold for amino acid-activated mechanistic target of rapamycin complex 1 (mTORC1), is critical for the polarization of M2 macrophages. However, little is known about how Lamtor1 affects the inflammatory responses that are triggered by the stimuli for TLRs. In this article, we show that Lamtor1 controls innate immune responses by regulating the phosphorylation and nuclear translocation of transcription factor EB (TFEB), which has been known as the master regulator for lysosome and autophagosome biogenesis. Furthermore, we show that nuclear translocation of TFEB occurs in alveolar macrophages of myeloid-specific Lamtor1 conditional knockout mice and that these mice are hypersensitive to intratracheal administration of LPS and bleomycin. Our observation clarified that the amino acid-sensing pathway consisting of Lamtor1, mTORC1, and TFEB is involved in the regulation of innate immune responses.

Allergic conversion of protective mucosal immunity against nasal bacteria in patients with chronic rhinosinusitis with nasal polyposis.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is characterized by eosinophilic inflammation and polyposis at the nose and paranasal sinus and a high concentration of IgE in nasal polyps (NPs). The causative antigen and pathogenesis of CRSwNP remain unknown. OBJECTIVE: We aimed to identify reactive allergens of IgE antibodies produced locally in NPs of patients with CRSwNP. We also attempted to unravel the differentiation pathway of IgE-producing B cells in NPs. METHODS: IgE reactivity of patients with CRSwNP was investigated by characterizing single cell-derived mAbs. T-cell response against identified allergens was investigated in vitro. NP-infiltrating lymphocytes were characterized by using flow cytometry. Immunoglobulins expressed in NPs were analyzed by using high-throughput DNA sequencing for immunoglobulin. RESULTS: About 20% of isolated IgE antibodies derived from NP-residing plasmablasts specifically recognized surface determinants of nasal bacteria, such as Staphylococcus aureus, Streptococcus pyogenes, and Haemophilus influenzae. A TH2 response against S pyogenes was observed in patients with CRSwNP. Flow cytometric analysis revealed sizable germinal center B-like cell and plasmablast subsets expressing IgE on the cell surface in NPs. High-throughput DNA sequencing immunoglobulin analysis highlighted the clonal connectivity of IgE with IgG and IgA1. The Iε-Cα1 circle transcript was detected in NPs. CONCLUSIONS: In patients with CRSwNP, nasal bacteria-reactive B cells differentiate into IgE-producing B cells through IgG/IgA1-IgE class switching, suggesting that allergic conversion of the mucosal response against nasal bacteria underlies disease pathogenesis.

[Two Cases of Venous Malformation of the Orbit Treated by Endoscopic Endonasal Surgery].

Venous malformation of the orbit(VMO), previously called orbital cavernous hemangioma, has been classified as a vascular malformation according to the International Society for the Study of Vascular Anomalies. Among various surgical approaches for VMO, endoscopic endonasal surgery(EES)has recently been developed, especially for those in the inferomedial quadrant of the orbit. Two 67-year-old and 69-year-old women presented with decreased visual acuity and visual field deficit, respectively. Their CT and MRI scans revealed retrobulbar masses, suggestive of the inferomedial type of VMO. The first case was diagnosed as an intraconal VMO, and subtotal removal was achieved through binostril EES using a two-surgeon four-handed technique after palliative partial resection through a prior frontal craniotomy. In the second case, diagnosed as an extraconal VMO, total en bloc removal was achieved using the same surgical technique as above. In both cases, the visual functions improved after the procedures, with uneventful postoperative courses. Although the inferomedial VMO is an uncommon type, EES is well indicated for this condition. The international consensus of surgical techniques and staging from a surgical point of view should be established in the near future.

mTOR Complex Signaling through the SEMA4A-Plexin B2 Axis Is Required for Optimal Activation and Differentiation of CD8+ T Cells.

Mammalian target of rapamycin (mTOR) plays crucial roles in activation and differentiation of diverse types of immune cells. Although several lines of evidence have demonstrated the importance of mTOR-mediated signals in CD4(+) T cell responses, the involvement of mTOR in CD8(+) T cell responses is not fully understood. In this study, we show that a class IV semaphorin, SEMA4A, regulates CD8(+) T cell activation and differentiation through activation of mTOR complex (mTORC) 1. SEMA4A(-/-) CD8(+) T cells exhibited impairments in production of IFN-γ and TNF-α and induction of the effector molecules granzyme B, perforin, and FAS-L. Upon infection with OVA-expressing Listeria monocytogenes, pathogen-specific effector CD8(+) T cell responses were significantly impaired in SEMA4A(-/-) mice. Furthermore, SEMA4A(-/-) CD8(+) T cells exhibited reduced mTORC1 activity and elevated mTORC2 activity, suggesting that SEMA4A is required for optimal activation of mTORC1 in CD8(+) T cells. IFN-γ production and mTORC1 activity in SEMA4A(-/-) CD8(+) T cells were restored by administration of recombinant Sema4A protein. In addition, we show that plexin B2 is a functional receptor of SEMA4A in CD8(+) T cells. Collectively, these results not only demonstrate the role of SEMA4A in CD8(+) T cells, but also reveal a novel link between a semaphorin and mTOR signaling.

The Endoscopic Removal of a Detached Dental Implant Cap in the Maxillary Sinus During the Waiting Period: A Case Report.

Displacement of dental implants into the maxillary sinus is one of the common dental complications. However, it is rare that dental implants cause the displacement of multiple components due to separation. Here, we describe an unusual case of a 43-year-old man who had a missing implant in the maxillary sinus after an implant procedure. There was a two-week waiting period before we performed the removal during which the cap had unexpectedly separated from the body and freely moved into the ostium by sinus activity. The body was independently extracted intraorally. The remaining cap was secondly removed by utilizing nasal endoscopy. There were no complications in the postoperative period and the patient reported no symptoms of sinusitis after two months of follow-up. We experience unexpected events in the course of treating a displaced implant into the maxillary sinus. Our case report may provide several learning points for the removal of a missing implant.

Understanding hereditary hemorrhagic telangiectasia: From genetic anomalies to systemic manifestations, quality of life, and epistaxis management-Exploring the otolaryngologist's integral role.

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Rendu-Weber syndrome, is a rare autosomal dominant disorder characterized by vascular malformations. This comprehensive review aimed to provide an overview and summarize various aspects of HHT, including the genetic abnormalities, complications associated with visceral arteriovenous malformations (AVMs), prognosis of HHT, quality of life (QOL), and treatment of epistaxis. In addition, this review highlights the challenges in diagnosing HHT and emphasizes the critical role of otolaryngologists in the early detection of HHT. Otolaryngologists can refer patients with refractory epistaxis for AVM screening to expedite intervention. Mutation of the genes involved in the transforming growth factor-ß signaling pathway leads to the incidence of HHT, resulting in the formation of abnormal blood vessel formation. These vascular malformations commonly manifest as telangiectasia on the skin and mucous membranes; however, epistaxis remains the hallmark symptom of HHT. The impact of HHT goes beyond the visible symptoms and often includes the formation of life-threatening visceral AVMs in the lungs, liver, and brain. The prognosis of patients with HHT is closely related to the development of these complications, necessitating timely diagnosis and intervention. Refractory epistaxis diminishes the QOL of patients with HHT. The management of epistaxis ranges from conservative measures to advanced interventions such as prevention, conservative treatments, ablation, surgical procedures, and the administration of anti-angiogenic agents. However, effective management requires a multidisciplinary approach. The diagnosis of HHT remains challenging due to its variable presentation and lack of awareness among physicians. This review highlights the importance of reducing the duration between symptom onset and diagnosis. Otolaryngologists who are experienced in the management of refractory epistaxis can aid in identifying potential cases of HHT. They can facilitate the initiation of screening for visceral AVMs via prompt recognition of the signs and symptoms of HHT, contributing to improved patient outcomes. Early detection and intervention through screening can extend the life expectancy of patients with HHT to levels comparable with that of the general population. In conclusion, this review provides insight into various aspects of HHT and emphasizes the importance of timely diagnosis and intervention in the mitigation of the potentially life-threatening complications associated with this disorder. Otolaryngologists play a critical role in this process, serving as gatekeepers to the identification of cases of HHT and implementation of appropriate screening and management pathways, thereby improving the life expectancy and QOL of patients.

Evaluation of odor recognition threshold measurement methods in T&T olfactometry: A survey study.

OBJECTIVE: The odor recognition thresholds in T&T olfactometry are measured by either the examiner's judgment of the patients' odor expression for each standard odor or by the patient's choice of the correct response from an olfactory term table. This study aimed to clarify the correct odor expressions and use of the olfactory term table. METHODS: A questionnaire was administered to otolaryngologists or medical staff in charge of testing at facilities where T&T olfactometry is performed. The questionnaire consisted of the facility's background, environment and procedures of T&T olfactometry, choice of the correct answer with five different standard odors, and use of the olfactory term table. For the choices, the expressions used were those considered correct at Nippon Medical School Tama Nagayama Hospital and the Kyoto Nose and Allergy Clinic. RESULTS: A total of 81 valid responses were obtained. Most respondents belonged to medical and educational institutions (59.3%, 48/81). The laboratories in the respondents' institutions were completely ventilated using various methods. Clinical laboratory technicians inspected 51.7% (45/81) of the facilities. The order of standard odors in the odor recognition threshold test differs depending on the facility. When the examiner was unsure about the answer given by the patient in the odor recognition threshold test, 16.1% (9/56) of the respondents chose "present the olfactory term table," 33.9% (19/56) chose "increase the concentration," and 37.5% (21/56) chose "present the olfactory term table" or "increase the concentration," depending on the situation. A total of 96.4% (54/56) of the facilities treated odor expressions other than those in the olfactory term table as correct, and the odor expressions that were considered correct differed from facility to facility. Of the respondents, 80.2% (65/81) answered "I know the olfactory term table," and the mean value of satisfaction with the current olfactory term table was 4.4 ± 3.0. Of the respondents, 81.5% (53/65) answered that "the timing of presenting the olfactory term table should be standardized in all facilities." CONCLUSION: In the odor recognition threshold test by T&T olfactometry, this study revealed that the odor expressions considered as correct answers for the standard odors and the use of the olfactory term table differed among facilities.

Neurectomy for allergic rhinitis in Japan: Increasing trends and surgeon preferences.

OBJECTIVE: There is no consensus on the optimal surgical technique for allergic rhinitis (AR). Furthermore, the appropriateness of surgical intervention in children and older individuals remains debatable. This study aimed to analyze trends and patterns in the surgical management of AR in Japan, focusing on parasympathetic neurectomy. METHODS: Using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), we conducted a comprehensive review of procedures performed between April 2014 and March 2022. In addition, a cross-sectional survey targeting otolaryngologists across Japan was conducted to gather insights into surgical preferences and practices. RESULTS: The NDB data showed an increasing trend in neurectomies, with the most frequent age group being 25-29 years; the procedure was also performed in pediatric and older patients. The survey among otolaryngologists indicated that 58.2 % of surgeons preferred peripheral branch neurectomy of the posterior nasal nerve. The findings of this study also indicated a cautious approach toward conducting these procedures in children, with 51.2 % of surgeons considering patients less than 18 years of age unsuitable for the procedure. CONCLUSION: This study highlighted a shift toward simple and minimally invasive surgical methods, such as peripheral branch neurectomy, in Japan. However, further research is needed to understand the long-term outcomes and refine the surgical techniques. The findings of this study also emphasized the need for age-specific considerations when treating pediatric and older patients with AR.

Sex Differences in Predicting Difficult Laryngeal Exposure: Validation and Modification of Predictive Models.

OBJECTIVES/HYPOTHESIS: To determine the presence of sex differences in difficult laryngeal exposure and the Laryngoscore, validate the Laryngoscore, mini-Laryngoscore, and Clarysse's model for predicting difficult laryngeal exposure, and modify the Laryngoscore for improved prediction accuracy. STUDY DESIGN: Retrospective study. METHODS: This study included 153 patients who underwent laryngeal microsurgery at a tertiary laryngology center and university hospital. Patients were evaluated using the 11 items of the Laryngoscore, mini-Laryngoscore, and Clarysse's model to predict difficult laryngeal exposure. Difficult laryngeal exposure was defined as the inability to view the anterior commissure through a rigid laryngoscope under counterpressure to the anterior neck. Descriptive statistics and receiver-operating characteristic curve analysis were used to assess the diagnostic performance of the predictive models and variables, including sex. RESULTS: The prevalence of difficult laryngeal exposure was significantly higher in men than in women, despite higher Laryngoscore values in females. The Laryngoscore, mini-Laryngoscore, and Clarysse's model demonstrated good diagnostic performance with C-indexes of 0.751, 0.727, and 0.783, respectively. Based on these findings, we proposed a modified Laryngoscore, including treatment history, interincisors gap, upper jaw dental status, thyro-mental distance, degree of neck flexion-extension, and sex, achieving a C-index of 0.835. CONCLUSIONS: Inclusion of sex in the Laryngoscore and related predictive models enhances the accuracy of predicting difficult laryngeal exposure. These findings support the inclusion of sex as a factor in future modifications of these models to improve their predictive performance.