International Consensus Statements on Intraoperative Testing for Cochlear Implantation Surgery.

OBJECTIVES: A wide variety of intraoperative tests are available in cochlear implantation. However, no consensus exists on which tests constitute the minimum necessary battery. We assembled an international panel of clinical experts to develop, refine, and vote upon a set of core consensus statements. DESIGN: A literature review was used to identify intraoperative tests currently used in the field and draft a set of provisional statements. For statement evaluation and refinement, we used a modified Delphi consensus panel structure. Multiple interactive rounds of voting, evaluation, and feedback were conducted to achieve convergence. RESULTS: Twenty-nine provisional statements were included in the original draft. In the first voting round, consensus was reached on 15 statements. Of the 14 statements that did not reach consensus, 12 were revised based on feedback provided by the expert practitioners, and 2 were eliminated. In the second voting round, 10 of the 12 revised statements reached a consensus. The two statements which did not achieve consensus were further revised and subjected to a third voting round. However, both statements failed to achieve consensus in the third round. In addition, during the final revision, one more statement was decided to be deleted due to overlap with another modified statement. CONCLUSIONS: A final core set of 24 consensus statements was generated, covering wide areas of intraoperative testing during CI surgery. These statements may provide utility as evidence-based guidelines to improve quality and achieve uniformity of surgical practice.

Aspiration prevention surgeries: a review.

BACKGROUND: Severe dysphagia can cause intractable pneumonia and lead to life-threatening conditions. Intractable aspiration can occur despite medical management for aspiration prevention. Surgical intervention is indicated for intractable aspiration to prevent potentially life-threatening complications. Since the 1970s, several surgical treatments to prevent aspiration have been reported, and various aspiration prevention surgeries have been introduced, but little is known about them or their benefits. This is a review of the types of aspiration prevention surgery, with the aim of increasing aspiration prevention surgery awareness and their clinical outcomes among medical professionals, which will guide the choices of aspiration prevention surgeries for patients with intractable aspiration. MAIN BODY: Aspiration prevention surgeries can be categorized into three according to their approaches: removal of the larynx, altering the structure of the trachea, and closure of the larynx. Aspiration prevention surgeries to remove the larynx include total and central-part laryngectomy. Aspiration prevention surgeries to alter the structure of the trachea include tracheoesophageal diversion, laryngotracheal separation, and the tracheal flap method. Surgeries to close the larynx can be divided into supraglottic laryngeal closure, glottic laryngeal closure, and subglottic laryngeal closure. Aspiration prevention surgeries prevent aspiration and increase oral intake in 50-80% of patients. Most patients lose vocal function after aspiration prevention surgeries; however, some patients who have undergone total laryngectomy or laryngotracheal separation restored their speech function through tracheoesophageal puncture and use of voice prosthesis. Postoperative suture failure is frequent after epiglottic flap closure and total laryngectomy but rare after central-part laryngectomy, laryngotracheal separation, glottic closure, and subglottic closure. Furthermore, aspiration prevention surgeries improve the quality of life of patients and their caregivers by decreasing suctioning frequency. CONCLUSIONS: In this review, we described the history and development of aspiration prevention surgeries. Medical professionals need to continually improve their knowledge and skills to facilitate appropriate aspiration prevention surgeries according to patient condition.

CDK12 alterations and ARID1A mutations are predictors of poor prognosis and therapeutic targets in high-grade salivary gland carcinoma: analysis of the National Genomic Profiling Database.

BACKGROUND: Due to the diversity of histopathologic types in salivary gland carcinoma, genomic analysis of large cohorts with next-generation sequencing by histologic type has not been adequately performed. METHODS: We analysed data from 93 patients with salivary duct carcinoma and 243 patients with adenoid cystic carcinoma who underwent comprehensive genomic profiling testing in the Center for Cancer Genomics and Advanced Therapeutics database, a Japanese national genome profiling database. We visualised gene mutation profiles using the OncoPrinter platform. Fisher's exact test, Kaplan-Meier analysis, log-rank test and Cox regression models were used for statistical analysis. RESULTS: In salivary duct carcinoma, a population with CDK12 and ERBB2 co-amplification was detected in 20 of 37 (54.1%) patients with ERBB2 amplification. We identified five loss-of-function variants in genes related to homologous recombination deficiency, such as BRCA2 and CDK12. Cox survival analysis showed that CDK12 and ERBB2 co-amplification is associated with overall survival (hazard ratio, 3.597; P = 0.045). In salivary duct carcinoma, NOTCH1 mutations were the most common, followed by mutations in chromatin modification genes such as KMT2D, BCOR, KDM6A, ARID1A, EP300 and CREBBP. In the multivariate Cox analysis, activating NOTCH1 mutations (hazard ratio, 3.569; P = 0.009) and ARID1A mutations (hazard ratio, 4.029; P = 0.034) were significantly associated with overall survival. CONCLUSION: CDK12 and ERBB2 co-amplification is associated with a poor prognosis in salivary duct carcinoma. Chromatin remodelling genes are deeply involved in tumour progression in adenoid cystic carcinoma. One such gene, ARID1A, was an independent prognostic factor. In salivary duct carcinoma and adenoid cystic carcinoma, there might be minor populations with mutations that could be targeted for treatment with the synthetic lethality approach.

Risk factors for incomplete resection with pharyngeal endoscopic submucosal dissection and long-term prognosis after resection.

BACKGROUND: Advances in endoscopic imaging technology have led to an increase in detection of superficial pharyngeal squamous carcinoma. Endoscopic submucosal dissection (ESD) has been reported to be effective for the treatment of these lesions, however there is still insufficient evidence on the long-term results of pharyngeal ESD. METHODS: This is a single-center retrospective study of all cases of superficial pharyngeal cancer that underwent ESD as primary treatment between January 2010 and May 2022. A total of 83 lesions in 63 patients were analyzed. RESULTS: The en bloc resection rate was 100%, and R0 resection rate was 59.0%, with an adverse event rate of 6.0%. During a mean observation period of 1134 days, there were 0 cases of disease-specific metastasis or death. However, the 5-year cumulative incidence of metachronous head and neck cancer after resection was 27.1% and the 5-year overall survival and 10-year overall survival after pharyngeal ESD were 87.0% and 69.6%, respectively. Of the 34 cases with non-R0 resection, local recurrence occurred in 8.8%. Location of lesion (p = 0.011), disparity between demarcation of the lesion with NBI and iodine staining (p = 0.026), and non-effective laryngeal elevation (p = 0.080) were risk factors for non-R0 resection. CONCLUSION: Pharyngeal ESD is effective and safe. Further studies are needed to improve and standardize indications and strategies for pharyngeal ESD.

Elective neck dissection for T3-T4N0 laryngeal carcinoma: evidence from Japan's National Head and Neck Cancer Registry.

BACKGROUND: Although total laryngectomy is the standard treatment for advanced laryngeal cancer, the significance of elective neck dissection (END) for N0 laryngeal cancer remains unclear in Japan, which is an aging society. METHODS: We conducted a retrospective nationwide observational study on patients with T3-T4N0 laryngeal squamous cell carcinoma treated with curative total laryngectomy from 2011 to 2018 in Japan. RESULTS: A total of 1,218 patients were analyzed. The median patient age was 72 years, with 735 cases of T3N0 and 483 cases of T4N0. END was performed on the affected side in 850 patients (70%) and on the contralateral side in 502 patients (41.2%). END on the affected side was omitted in patients aged > 80 years (40.4%) and in patients with an advanced performance status. The occult lymph-node metastasis rate did not differ by age (18.8%-19.6%); it tended to increase chronologically from 2011 (11.1%) and was higher in cT4a (22.5%) and pT4a (24.3%) cases. In this study, coherent clinical information and follow-up data were available for 252 patients. Both univariate and multivariate analyses showed no significant prognostic factors for overall survival or recurrence-free survival for either affected or contralateral END. Older age and subglottic location were poor prognostic factors, but death due to factors other than laryngeal cancer could not be ignored in older patients. CONCLUSION: Omission of END during laryngectomy for T3-T4N0 laryngeal cancer is acceptable for older patients who want their operation to be completed in a short time.

Hearing and Hearing Loss Progression in Patients with GJB2 Gene Mutations: A Long-Term Follow-Up.

We aimed to investigate whether the degree of hearing loss with GJB2 mutations could be predicted by distinguishing between truncating and non-truncating mutations and whether the genotype could predict the hearing loss level. Additionally, we examined the progression of hearing loss in individuals monitored for over 2 years for an average of 6.9 years. The proportion of truncating mutations was higher in patients with profound and severe hearing loss, but it was not accurate enough to predict the degree of hearing loss. Via genotype analysis, mutations of the p.Arg143Trp variants were associated with profound hearing loss, while mutations of the p.Leu79Cysfs*3 allele exhibited a wide range of hearing loss, suggesting that specific genotypes can predict the hearing loss level. Notably, there were only three cases of progression in four ears, all of which involved the p.Leu79Cysfs*3 mutation. Over the long-term follow-up, 4000 Hz was significant, and there was a trend of progression at 250 Hz, suggesting that close monitoring at these frequencies during follow-up may be crucial to confirm progression. The progression of hearing loss was observed in moderate or severe hearing loss cases at the time of the initial diagnosis, emphasizing that children with this level of hearing loss need regular follow-ups.

Tumor-stroma ratio can predict lymph-node metastasis in cT1/2N0 oral tongue squamous cell carcinoma independent of tumor budding grade.

BACKGROUND: cT1/2 oral tongue squamous cell carcinoma (OTSCC) often metastasizes to cervical lymph nodes. However, predicting neck lymph-node metastasis (NLM) remains challenging. Pathomorphological evaluation of tumor budding grade (TBG) and tumor-stroma ratio (TSR) reportedly can predict lymph-node metastases. Hence, this study aimed to evaluate TBG and TSR in OTSCC and investigate their relationship to occult NLM and cancer relapse. METHODS: Clinicopathological data of patients with cT1/2N0 OTSCC treated at the University of Tokyo Hospital between 2007 and 2017 were collected. TBG and TSR were evaluated using hematoxylin-eosin staining and cytokeratin AE1/AE3 immunostaining. RESULTS: Out of 70 patients, 16 underwent elective neck dissection in addition to primary-tumor resection, whereas 54 did not. During follow-up, NLM was found in 35 patients. NLM correlated with the pathological depth of invasion (pDOI) (p < 0.001), TBG (p = 0.008), and TSR (p < 0.001) in univariate analysis and pDOI (p = 0.01) and TSR (p = 0.02) in multivariate analysis. The 5-year recurrence-free survival rate (RFS) was 78% for patients with a pDOI ≤ 5 mm and stroma-poor tumors and 33% for patients with a pDOI > 5 mm and stroma-rich tumors. CONCLUSION: Patients with a pDOI > 5 mm and stroma-rich tumors have a high risk for cancer relapse. TSR and pDOI may be promising NLM predictors in cT1/2N0 OTSCC.

Safety of surgical tracheostomy under continued antithrombotic therapy: A retrospective cohort study.

OBJECTIVE: Although various guidelines have been established for the management of antithrombotic therapy during surgical treatments, surgical tracheostomy (ST) under continued antithrombotic therapy (CAT) remains challenging. Here, we investigated the risk factors for complications after ST by focusing on the application of CAT during ST. DESIGN: A retrospective cohort study with medical records from 2009 to 2020. SETTING: A single-center study. PARTICIPANTS: This study included patients who had undergone ST at the Department of Otolaryngology of our hospital MAIN OUTCOME MEASURES: The primary outcomes were the incidence of complications and blood test results. Secondary outcomes were risk factors for postoperative complications. RESULTS: We identified 288 patients (median age: 64 years; 184 men [64%]), among whom 40 (median age: 67 years; 29 men [73%]) underwent CAT. Although the patients undergoing CAT had significantly longer activated partial thromboplastin time (p=0.002) and a higher prothrombin time-international normalized ratio (p=0.006) compared to antithrombotic naïve patients, no statistically significant intergroup differences were observed for the risk of bleeding, infection, or subcutaneous emphysema. Instead, ST under local anesthesia (p=0.01) and ST for airway emergency (p=0.02) significantly increased the risk of early postoperative complications. CONCLUSION: These results suggest that ST under CAT can be safely performed without any increased risk of postoperative complications. Nevertheless, surgeons should be extra cautious about early complications after ST under local anesthesia without intubation or ST for airway emergencies.

Fluorescence Probes for Imaging Basic Carboxypeptidase Activity in Living Cells with High Intracellular Retention.

Basic carboxypeptidases (basic CPs) cleave the C-terminal basic amino acid of peptides, and their activity is upregulated in some types of cancers. Therefore, detecting the activity of basic CPs in living cells would be important not only for studying the physiological functions of these enzymes but also for visualization of cancerous tissues. Here, we report two fluorescein diacetate (FDA)-based activatable fluorescence probes, named 5ArgAF-FDA and 5LysAF-FDA, in which the substrate amino acid arginine or lysine is conjugated to the benzene moiety via an azoformyl linker. In live-cell fluorescence imaging of CPM, one of the seven basic CPs, 5ArgAF-FDA showed a larger intracellular fluorescence increase than did 5LysAF-FDA within a few minutes. This increase was inhibited by coincubation with 2-mercaptomethyl-3-guanidinoethylthiopropanoic acid (MGTA), an inhibitor of basic CPs. When 5ArgAF-FDA was applied to a coculture of two breast cancer cell lines with different CPM activities, the fluorescence increase in individual cells was correlated with the expression level of CPM, suggesting that 5ArgAF-FDA has the ability to distinguish cell lines having different levels of CPM activity, owing to its high intracellular retention. We believe these probes will be useful for imaging cancers with upregulated basic CP activity.

Vascular Bursts Act as a Versatile Tumor Vessel Permeation Route for Blood-Borne Particles and Cells.

Dynamic bursting in tumor vasculature has recently sparked interest as a novel particle transportation route for drug delivery. These bursts facilitate the transport of sub-100 nm nanoparticles into tumors, though their contribution on the access of other blood-borne particles remains unknown. To evaluate the versatility of this phenomenon, the in vivo kinetics of a variety of intravenously injected particles and their penetration in tumor xenografts and allografts are compared. Dextran, polymeric micelles, liposomes, and polymeric vesicles with diameters ranging from 32 to 302 nm are found to colocalize in virtually all vascular bursts. By mathematical modeling, the burst vent size is estimated to be 625 nm or larger, indicating the dynamic and stochastic formation of large permeation routes in tumor vasculature. Furthermore, some burst vents are found to be µm-sized, allowing the transport of 1 µm microspheres. Moreover, antibody drugs and platelets are capable of utilizing vascular burst transportation, demonstrating the application of this phenomenon to other types of therapeutics and cellular components. These findings indicate the vast potential of vascular bursts, extending the biological and therapeutic significance of this phenomenon to a wide range of blood-borne particles and cells.

A murine model of eosinophilic chronic rhinosinusitis using the topical application of a vitamin D3 analog.

BACKGROUND: Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory disease, characterized by eosinophilic infiltration, T-helper type 2 (Th2-type) response, and olfactory dysfunction. A master regulator of Th2-type inflammation, thymic stromal lymphopoietin (TSLP), is important for basophil activation. TSLP-elicited basophils are a key factor in the pathogenesis of ECRS. METHODS: In order to elucidate the mechanisms of ECRS in humans, we aimed to establish a murine model of ECRS based on TSLP production in response to the topical application of MC903 (a vitamin D3 analog) and the subsequent TSLP-induced basophil activation. Histological analyses were performed to assess immune cell infiltration into the nasal mucosa and to explore the impact of eosinophilic inflammation on the olfactory epithelium. The status of Th2-type inflammation was evaluated by quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA). RESULTS: Eosinophils, basophils, and M2 macrophages increased significantly in the nasal mucosa of the mice treated with MC903 and ovalbumin (OVA), compared to those treated with OVA alone or the controls. Quantitative real-time PCR and ELISA revealed elevated expression of interleukin (IL)-4, IL-5, IL-13, TSLP, the chemokine CCL11, and CCL24 in the nasal mucosa of the ECRS mice. In parallel, thinned olfactory epithelium and decreased mature olfactory sensory neurons were observed in the ECRS mice. CONCLUSIONS: Our model of ECRS displayed Th2-type inflammation in the sinonasal region, including both eosinophil infiltration and basophil infiltration. Additionally, olfactory epithelium turned out to be affected by eosinophilic inflammation. These features are consistent with the characteristics of the human ECRS.

Cervical Vestibular Evoked Myogenic Potentials That Are Absent at 500 Hz But Present at 1000 Hz Are Characteristic of Endolymphatic Hydrops-Related Disease.

OBJECTIVES: It remains unclear whether the dominance of 1000 Hz responses over responses at 500 Hz in cervical vestibular evoked myogenic potentials (cVEMPs) are characteristic of endolymphatic hydrops (EH), due to the presence of patients with absent responses at both frequencies. The purpose of the present study is to examine whether the dominant cVEMP responses at 1000 Hz over 500 Hz are characteristic findings of EH-related diseases among patients who show various cVEMP findings. DESIGN: We retrospectively reviewed the medical records of 470 consecutive patients who underwent cVEMP testing with short-tone bursts at both 500 Hz and 1000 Hz. We categorized the cVEMP responses of these 470 patients into the following five groups: (group 1) present responses at both frequencies bilaterally, (group 2) present responses at 500 Hz but absent at 1000 Hz on at least one side, (group 3) absent responses at 500 Hz but present at 1000 Hz on at least one side, (group 4) absent responses at both frequencies on one side and present at both frequencies on the other side, and (group 5) absent responses at both frequencies bilaterally. We compared the proportion of EH-related diseases between each group and the other four groups and then investigated any increased or decreased disease incidence in each group. RESULTS: In group 3, the proportion of EH-related disease was significantly higher (p < 0.01), and the incidence of an EH-related disease was greatly increased (standard residual value > 3). CONCLUSIONS: cVEMPs that are absent at 500 Hz and present at 1000 Hz may be characteristic of EH-related disease.

Aspiration Prevention Surgery under Local Anesthesia for Palliative Care in Patients with Head and Neck Cancer: A Report of Two Cases.

Aspiration prevention (AP) surgery may improve the quality of life (QOL) of patients with severe dysphagia. However, not all patients can endure this type of surgery under general anesthesia because of their poor status. Herein, we describe the cases of 2 patients with head and neck cancer (HNC) who underwent AP surgery for palliative care. Although both patients had tracheostomy due to severe dysphagia and respiratory impairment and frequently needed suction, they were successfully managed with AP surgery under local anesthesia. A tracheostoma was reshaped to be sufficiently large for an airway to be secured without a cannula. Their respiratory failure gradually improved, and suction frequency markedly decreased after surgery; thus, they could receive medical treatment at home. When patients with HNC under palliative care have a tracheal cannula and cannot vocalize, AP surgery under local anesthesia is an option to improve their QOL.

The effects of barium concentration levels on the pulmonary inflammatory response in a rat model of aspiration.

PURPOSE: Barium sulfate (Ba) suspension is the most widely used contrast agent for upper gastrointestinal and videofluoroscopic swallow studies (VFSS). The effect of Ba concentration on lung injury is uncertain. The aims of this study were to explore the effects of different barium concentrations on the respiratory organs and elucidate the underlying mechanisms of these effects in an established animal model of aspiration. METHODS: Animal model study. Eight-week-old male Sprague-Dawley rats were allocated into three groups (n = 12, each group). Two groups underwent tracheal instillation of low (30% w/v) and high (60% w/v) concentration Ba (low-Ba, high-Ba). A control group was instilled with saline. Half of the animals were euthanized on day 2 and the remaining half were euthanized on day 30. Histological and gene analyses were performed. RESULTS: Both low-Ba and high-Ba aspiration caused inflammatory cell infiltration in the lung at 2 days post aspiration with an increase in the expression of inflammatory cytokines. At 30 days post aspiration, small quantities of barium particles remained in the lung of the low-Ba group without any inflammatory reaction. Chronic inflammation was recognized in the high-Ba group up to 30 days post aspiration. CONCLUSION: A small amount of high concentration Ba (60% w/v) caused sustained inflammation in the rat lung at least 30 days after aspiration. Even with a small amount of low concentration Ba aspiration (30% w/v), Ba particles can remain in the lung over a month, causing sustained late effects.

Caloric restriction reduces basal cell proliferation and results in the deterioration of neuroepithelial regeneration following olfactotoxic mucosal damage in mouse olfactory mucosa.

The effects of caloric restriction (CR) on cell dynamics and gene expression in the mouse olfactory neuroepithelium are evaluated. Eight-week-old male C57BL/6 mice were fed either control pellets (104 kcal/week) or CR pellets (67 kcal/week). The cytoarchitecture of the olfactory neuroepithelium in the uninjured condition and its regeneration after injury by an olfactotoxic chemical, methimazole, were compared between mice fed with the control and CR diets. In the uninjured condition, there were significantly fewer olfactory marker protein (OMP)-positive olfactory receptor neurons and Ki67-positive proliferating basal cells at 3 months in the CR group than in the control group. The number of Ki67-positive basal cells increased after methimazole-induced mucosal injury in both the control and the CR groups, but the increase was less robust in the CR group. The recovery of the neuroepithelium at 2 months after methimazole administration was less complete in the CR group than in the control group. These histological changes were region-specific. The decrease in the OMP-positive neurons was prominent in the anterior region of the olfactory mucosa. Gene expression analysis using a DNA microarray and quantitative real-time polymerase chain reaction demonstrated that the expression levels of two inflammatory cytokines, interleukin-6 and chemokine ligand 1, were elevated in the olfactory mucosa of the CR group compared with the control group. These findings suggest that CR may be disadvantageous to the maintenance of the olfactory neuroepithelium, especially when it is injured.

Use of intensity-modulated radiation therapy for nasopharyngeal cancer in Japan: analysis using a national database.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) yields better outcomes and fewer toxicities for radiation therapy (RT) of head and neck cancers (HNCs), including nasopharyngeal cancer (NPC). IMRT is the standard RT treatment and has been widely adopted in Western countries to treat HNCs. However, its uptake in clinical practice among NPC patients has never been studied. METHODS: We investigated the use of IMRT for NPC using data from a nationwide cancer registry to describe the use of IMRT among NPC patients in Japan. We analyzed the data of patients with HNC, including NPC, who underwent IMRT between 2012 and 2014, as recorded in the hospital-based cancer registries linked with insurance claims. We calculated the proportion of patients with NPC who underwent IMRT at each hospital. To evaluate the use of IMRT for NPC, the IMRT use for NPC was compared with the proportion of patients with prostate cancer who underwent IMRT. RESULTS: Among 508 patients with NPC who underwent RT at one of 87 hospitals, 348 (69%) underwent IMRT. This proportion gradually increased between 2012 and 2014 (62%, 64% and 77%). Meanwhile, 4790 patients with prostate cancer (90%) underwent IMRT. Although some hospitals where IMRT was performed treated many patients with NPC, the proportion of patients with NPC who were treated with IMRT was low. CONCLUSIONS: IMRT has not been widely adopted in Japan for treating NPC. Barriers for adopting its use should be identified to close the gap between the standard and actual medical practice in Japan.

Outcomes of endoscopic sinus surgery for sinusitis-induced intracranial abscess in patients undergoing neurosurgery.

OBJECTIVE: Although sinusitis-induced intracranial complications rarely occur in the current era of antibiotics, they can induce neurological symptoms or death. The authors of this study investigated the association between endoscopic sinus surgery (ESS) and outcomes in patients who had undergone neurosurgical procedures for sinusitis-induced intracranial abscess. METHODS: The authors obtained data on patients with sinusitis-induced intracranial abscess from the Japanese Diagnosis Procedure Combination inpatient data for the period from 2010 to 2017. They excluded patients with fungal sinusitis, orbital complications, immunodeficiency, and malignant disease. They also excluded patients who had received antifungal agents, chemotherapy, immunosuppressants, and antidiabetic drugs. Eligible patients were divided into those with and those without neurosurgical procedures. Propensity score-adjusted regression analyses were performed to examine the association between ESS within the same hospitalization and outcomes (mortality, blood transfusion, readmission, revision neurosurgery, and length of stay). RESULTS: Of the 552 potentially eligible patients, 255 were treated with neurosurgical procedures, including 104 who underwent ESS within the same hospitalization and 151 who did not. ESS was not significantly associated with mortality (OR 0.54, 95% CI 0.05-5.81, p = 0.61), blood transfusion (OR 1.95, 95% CI 0.84-4.51, p = 0.12), readmission (OR 0.86, 95% CI 0.34-2.16, p = 0.75), revision neurosurgery (OR 0.65, 95% CI 0.24-1.74, p = 0.39), or length of stay (percent difference -10.8%, 95% CI -24.4% to 5.1%, p = 0.18). CONCLUSIONS: The present study suggests that ESS may not have significant benefits with respect to reducing mortality, blood transfusion, readmission, revision neurosurgery, or length of stay.

Tranexamic acid and post-tonsillectomy hemorrhage: propensity score and instrumental variable analyses.

PURPOSE: Although post-tonsillectomy hemorrhage occurs rarely, it can be life-threatening. Previous studies showed that tranexamic acid (TXA) had insignificant association with the rate of post-tonsillectomy hemorrhage, but those findings were limited by small sample sizes. The purpose of this study was to examine the effectiveness of TXA in preventing post-tonsillectomy hemorrhage using nationwide database. METHODS: Data of a retrospective cohort of 117,598 patients from 750 hospitals, who had undergone tonsillectomy between 2010 and 2016, were drawn from the Diagnosis Procedure Combination database in Japan and studied. RESULTS: Propensity score-matched analysis showed no significant differences in proportions of reoperation or blood transfusion after tonsillectomy between the treatment (TXA from the day of tonsillectomy) and control groups (1.50% vs. 1.47%, p = 0.64). Instrumental variable analysis also showed no significant differences (odds ratio, 0.98; 95% confidence interval, 0.86-1.13; p = 0.82). Higher proportions of reoperation or blood transfusion were significantly associated with male sex, older age, emergency hospitalization, prolonged anesthesia, and medium hospital volume (annual number of tonsillectomies). CONCLUSIONS: Administration of TXA from the day of tonsillectomy is not associated with reduction in reoperation or blood transfusion rates.

Investigation of the Safety of Injection Laryngoplasty under Antithrombotic Therapy.

BACKGROUND: Glottic insufficiency negatively affects phonation and swallowing function. Injection laryngoplasty is a convenient and minimally invasive treatment for glottic insufficiency. This study assessed whether injection laryngoplasty is safe under continued administration of antithrombotic drugs, and aimed to establish measurable laboratory values under which such a procedure can be safely performed. METHOD: This retrospective medical record review covered the period from November 2012 to June 2018. We examined 17 patients who underwent injection laryngoplasty (47 injections) under continued administration of antithrombotic drugs at the University of Tokyo Hospital. We analyzed clinical and demographic profiles, complications, and blood test values. Statistical analyses were performed regarding the risks of complications due to injection side, route of administration, and number of antithrombotic drugs. RESULTS: No patients exhibited airway narrowing or dyspnea; however, bleeding after injection laryngoplasty was observed in 3 patients. All patients exhibited values within the optimal treatment range. There were no significant differences regarding the risks of complications due to injection side, route of administration, or number of antithrombotic drugs. CONCLUSIONS: When the platelet count, prothrombin time-international normalized ratio, and activated partial thromboplastin time were within the optimal range prior to treatment, injection laryngoplasty could safely be performed, regardless of the administration of antithrombotic drugs.

The adhesion molecule cadherin 11 is essential for acquisition of normal hearing ability through middle ear development in the mouse.

Cadherin 11 (Cdh11), a member of the cadherin adhesion molecule family, is expressed in various regions of the brain as well as the head and ear. To gain further insights into the roles of Cdh11 in the development of the ear, we performed behavioral tests using Cdh11 knockout (KO) mice. KO mice showed reduced acoustic startle responses and increased thresholds for auditory brainstem responses, indicating moderate hearing loss. The auditory bulla volume and ratio of air-filled to non-air-filled space in the middle ear cavity were reduced in KO mice, potentially causing conductive hearing loss. Furthermore, residual mesenchymal and inflammatory cells were observed in the middle ear cavity of KO mice. Cdh11 was expressed in developing mesenchymal cells just before the start of cavitation, indicating that Cdh11 may be directly involved in middle ear cavitation. Since the auditory bulla is derived from the neural crest, the regulation of neural crest-derived cells by Cdh11 may be responsible for structural development. This mutant mouse may be a promising animal model for elucidating the causes of conductive hearing loss and otitis media.