Investigation of the Position and Angle of the Vocal Fold Projected onto the Thyroid Cartilage.

OBJECTIVE: To perform laryngeal framework surgery for unilateral vocal fold paralysis and obtain favorable voice improvement, it is necessary to accurately determine the vocal fold and arytenoid cartilage positions. Thus, the position and angle of the paralyzed vocal folds and arytenoid cartilage projected onto the affected thyroid plate were measured using computed tomography (CT) before and after surgery. METHODS: Forty-six male patients with thyroid cartilage ossification observed on preoperative CT and vocal fold paralysis were included. Using Adobe Illustrator®, the thyroid plate on the affected side was reconstructed from the continuous images of the sagittal section of the CT examination during participant's quiet breathing (reconstructed affected thyroid plate [RATP]). RESULTS: The anterior commissure mean position was slightly cranial to the midpoint of the thyroid cartilage midline. The paralyzed vocal fold angle was not parallel to the baseline. The average unaffected vocal fold angle during vocalization projected onto the affected thyroid plate was 13.83°, which differed significantly from the average paralyzed vocal fold angle before surgery (19.05°). However, no significant difference was observed in comparison with the average angle of the paralyzed vocal fold after arytenoid adduction. The average distance from the inferior notch of the affected side thyroid cartilage to the affected arytenoid cartilage was 16.7 mm. CONCLUSION: By understanding the positional relationship between the thyroid cartilage plate and internal structure from preoperative CT images, more effective surgery can be performed according to individual differences. LEVEL OF EVIDENCE: IV Laryngoscope, 2024.

Blocking DCIR mitigates colitis and prevents colorectal tumors by enhancing the GM-CSF-STAT5 pathway.

Dendritic cell immunoreceptor (DCIR; Clec4a2), a member of the C-type lectin receptor family, plays important roles in homeostasis of the immune and bone systems. However, the intestinal role of this molecule is unclear. Here, we show that dextran sodium sulfate (DSS)-induced colitis and azoxymethane-DSS-induced intestinal tumors are reduced in Clec4a2-/- mice independently of intestinal microbiota. STAT5 phosphorylation and expression of Csf2 and tight junction genes are enhanced, while Il17a and Cxcl2 are suppressed in the Clec4a2-/- mouse colon, which exhibits reduced infiltration of neutrophils and myeloid-derived suppressor cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) administration ameliorates DSS colitis associated with reduced Il17a and enhanced tight junction gene expression, whereas anti-GM-CSF exacerbates symptoms. Furthermore, anti-NA2, a ligand for DCIR, ameliorates colitis and prevents colorectal tumors. These observations indicate that blocking DCIR signaling ameliorates colitis and suppresses colonic tumors, suggesting DCIR as a possible target for the treatment of these diseases.

Immunogenic tumor cell death promotes dendritic cell migration and inhibits tumor growth via enhanced T cell immunity.

Immunogenic tumor cell death enhances anti-tumor immunity. However, the mechanisms underlying this effect are incompletely understood. We established a system to induce tumor cell death in situ and investigated its effect on dendritic cell (DC) migration and T cell responses using intravital photolabeling in mice expressing KikGR photoconvertible protein. We demonstrate that tumor cell death induces phagocytosis of tumor cells by tumor-infiltrating (Ti)-DCs, and HMGB1-TLR4 and ATP-P2X7 receptor signaling-dependent Ti-DC emigration to draining lymph nodes (dLNs). This led to an increase in anti-tumor CD8+ T cells of memory precursor effector phenotype and secondary tumor growth inhibition in a CD103+ DC-dependent manner. However, combining tumor cell death induction with lipopolysaccharide treatment stimulated Ti-DC maturation and emigration to dLNs but did not improve tumor immunity. Thus, immunogenic tumor cell death enhances tumor immunity by increasing Ti-DC migration to dLNs where they promote anti-tumor T cell responses and tumor growth inhibition.

Long-term treatment outcome of type 1 thyroplasty using novel titanium medialization laryngoplasty implant combined with arytenoid adduction for unilateral vocal cord paralysis: single-arm interventional study at a single institution.

OBJECTIVE: To evaluate the long-term treatment outcome of type 1 thyroplasty with novel rearrangeable titanium medialization laryngoplasty implant (TMLI) combined with arytenoid adduction (AA) for unilateral vocal cord paralysis (UVFP) in the authors' institution. METHODS: A total of 16 Japanese patients with UVFP who received type 1 thyroplasty using TMLI with arytenoid adduction was enrolled in this single-arm, non-randomized interventional study. The results of the auditory perceptual assessment, aerodynamic examination, acoustic measurement, and patient-based survey on these patients were evaluated preoperatively and at 3, 6, and 12 months postoperatively. RESULTS: Type 1 thyroplasty using TMLI with arytenoid adduction for our patient series presented significant improvements in maximum phonation time, mean flow rates, GRBAS scale, the Voice Handicap Index and the Voice-Related Quality of Life score over the 12-month postoperative period. CONCLUSION: Type 1 thyroplasty using TMLI with arytenoid adduction was quite effective for obtaining satisfactory postoperative voice improvement without any surgical complication over the long-term period.

Bilateral vocal fold immobility: Clinical findings of ten cases and suggested treatment options.

OBJECTIVE: To present the clinical findings of 10 cases of bilateral vocal fold immobility (adducted type) and suggest potential treatment options. METHODS: This retrospective study included 10 patients who underwent tracheostomy for restricted airway due to bilateral vocal fold immobility of the adducted type during the period from 2007 to 2017. All 10 patients underwent unilateral laterofixation surgery with or without additional arytenoidectomy using a CO2 laser. The effect of laterofixation surgery for decannulation was evaluated. Statistical analysis was performed to assess the effects of laterofixation based on the results of preoperative and intraoperative examinations including endoscopic examinations, electromyography, and the intraoperative traction-mobility test. RESULTS: Initial laterofixation surgery for decannulation was effective in 6 cases. In the 4 cases that exhibited laterofixation failure, additional endoscopic subtotal arytenoidectomy was performed. Statistical analysis of the effects of laterofixation revealed that, in cases with bilateral preserved muscle tone, unilateral simple laterofixation surgery was unable to achieve a significantly effective glottal airway. Additional subtotal arytenoidectomy was also ineffective in a case with bilateral ankylosis. CONCLUSION: Based on the clinical findings in these 10 cases of bilateral vocal fold immobility of the adducted type, treatment options are suggested and a severity classification system of bilateral vocal fold immobility is proposed that focuses mainly on electromyography results for assessment of dynamic restenosis and traction-mobility test results for assessment of static restenosis. Validation of the classification system is needed in a larger cohort of cases of bilateral vocal fold immobility.

Therapeutic Efficacy of Basic Fibroblast Growth Factor in Patients With Vocal Fold Atrophy.

OBJECTIVES/HYPOTHESIS: In recent years, basic fibroblast growth factor (bFGF) injection has been used in the treatment of aging-related vocal fold atrophy. This injection not only improves closure by increasing the mass of the vocal fold but also improves its viscoelasticity. However, it has been reported that fibroblasts targeted by bFGF treatment decrease in number with age. The purpose of this study was to examine the effects of local injection of bFGF on age-related vocal atrophy as well as the influence of age on phonological outcomes. STUDY DESIGN: Retrospective chart review. METHODS: Fifty-three patients with age-related vocal fold atrophy underwent single injections of bFGF in their vocal folds. Phonological outcomes were evaluated 3 and 6 months after injection by acoustic and aerodynamic measurements. RESULTS: Voice Handicap Index (VHI), maximum phonation time (MPT), jitter, shimmer, and pitch range improved after injection, and the effects continued for 6 months. In those over 70 years of age, VHI and MPT showed improvement at 3 and 6 months after injection. In addition, the degree of improvement in VHI and MPT did not differ significantly between those older than 70 years and those younger than 70 years. CONCLUSIONS: Regenerative treatments dependent on bFGF single injection was safe and effective for both early and late elderly patients suffering of vocal fold atrophy. LEVEL OF EVIDENCE: 2c Laryngoscope, 2020.

IgG4-related disease with pseudotumor formation in the larynx.

Mikulicz's disease, an immunoglobulin G4-related disease (IgG4-RD) occurs frequently in the head and neck region but rarely in the larynx. We report a case of IgG4-RD with pseudotumor formation in the larynx. A 50-year-old man presented at our facility for a complete physical examination and diagnostic testing of a left arytenoid tumor. On examination, a large supraglottic mass was noted with signs of dyspnea. Movement disorder of the vocal fold was absent. The patient underwent surgery with general anesthesia to improve respiratory symptoms and a resected specimen was submitted for diagnosis. The pathology findings revealed lymph follicle formation, interstitial follicular fibrosis, angiogenesis, and inflammatory cell infiltration with plasmacytosis. Immunohistologic staining at high magnification revealed one hundred or more IgG4-positive plasma cells and fifty percent IgG4/IgG. In addition, obliterative phlebitis was observed. Medical history was positive for retroperitoneal fibrosis with serum IgG4 levels below the diagnostic criteria of IgG4-RD, but histological characteristics of IgG4-RD were met. The diagnosis of IgG4-RD was established, oral treatment with prednisolone (0.6 mg/kg/day) was initiated, and the tumor reduced in size. IgG4-RD may cause irreversible functional impairment. Early diagnosis and treatment are important in reducing the risk of permanent impairment of vocal fold mobility.

Operative Procedure of Anterior Commissure for Type II Thyroplasty.

OBJECTIVE: We reviewed the clinical anatomy of the anterior commissure and examined the effectiveness of a specialized spreader developed for optimal, efficient spreading of the thyroid cartilage in type II thyroplasty. STUDY DESIGN AND METHODS: The present study was a multicenter retrospective study of patients with spasmodic dysphonia who underwent a primary operation either before or after the introduction of a specialized spreader (in 2008 or 2014, respectively). In these patients, we examined the size of the titanium bridge used, the presence of perforation of the mucosa directly superior to the anterior commissure, and postoperative glottic findings. RESULTS: The sample comprised 39 and 40 patients who underwent surgery in 2008 and 2014, respectively. The mean size of the titanium bridge used during surgery was significantly smaller in 2014 (2.9 mm) than in 2008 (3.81 mm). Perforation of the laryngeal mucosa occurred in 13 patients in 2008 but occurred in only one patient in 2014. Based on glottic findings, spreading the thyroid cartilage using the specialized spreader was deemed to yield an effective glottic gap. CONCLUSIONS: In type II thyroplasty, the handling of the anterior commissure is the most important point. It is necessary to split the tendon and to spread the glottis while the tendon is joined with the cartilage. For this purpose, a specialized spreader was made. The use of a specialized spreader renders separation around the anterior commissure unnecessary, enabling minimally invasive spreading of the thyroid cartilage and thereby improving phonation.

Injection of basic fibroblast growth factor for unilateral vocal cord paralysis.

OBJECTIVE: Unilateral vocal cord paralysis (UVCP) not only induces severe dysphonia, but aspiration as well. Although laryngeal framework surgery is usually performed to treat this condition, the procedure is not tolerated by some patients. In the previous study, basic fibroblast growth factor (bFGF) injections for vocal cord scarring and sulcus have been reported to provide favorable outcomes while being minimally invasive. In this study, the authors retrospectively investigated phonological outcomes after bFGF injection in patients with UVCP. METHODS: This study was registered in University hospital Medical Information Network - Clinical Trials Registry (UMIN000019347). Nineteen patients with unilateral cord paralysis were treated with bFGF injection. The treatment regimen involved a single injection of 50 µg of bFGF into the muscle layer. More than six months after the injection, aerodynamic and acoustic outcomes were examined. RESULTS: The voice handicap index, maximum phonation time, mean airflow rate, and pitch range improved significantly after injection of bFGF. No sex-related differences were observed in any phonological parameter. CONCLUSION: bFGF injection, an easy method and suitable as an office procedure, significantly improved the hoarseness caused by UVCP. It is expected to be widely adopted and effective adjunctive drugs, and procedures are anticipated to be developed.

Transcricothyroid Endoscopic Subglottic Surgery for Posterior Glottic Stenosis: A Case Report.

Posterior glottic stenosis (PGS) is a rare but life-threatening condition mostly caused by damage to the interarytenoid mucosa by an endotracheal tube. In surgical treatment of PGS, airway patency is prioritized, and the laryngeal functions involved in swallowing and phonation are considerably sacrificed. In the majority of cases, lateralization of a vocal fold or partial excision of a vocal fold and arytenoid cartilage results in glottal closure insufficiency and deterioration of phonatory function. We present the first report of transcricothyroid endoscopic subglottic surgery to treat a 46-year-old man with PGS who was intubated for 10 days. Postoperative hypofunction was not observed in the aerodynamic examination and acoustic analysis, and phonatory function has been maintained within normal limits.

[Investigation of Type I Thyroplasty Using Titanium Implant].

OBJECTIVE: The aim of this study was to describe a new titanium thyroplasty medializing implant and evaluate its usefulness. MATERIAL AND METHOD: Retrospective study of 9 male patients with severe unilateral vocal fold paralysis after aortic-aneurysm surgery who underwent type I thyoplasty with arytenoid adduction under general anesthesia. Preoperative and postoperative glottal closure and voice function were evaluated by acoustic analysis (Jitter %, Shimmer %, NHR), stroboscopic findings, maximum phonation time, mean airflow rate, voice handicap index and computed tomography findings. These tests were evaluated before and 3 months after surgery. RESULT: All acoustic parameters improved after surgery. In stroboscopic findings, symmetrical mucosal waves were identified in 3 cases. Maximum phonation time prolonged, mean flow rate decreased and voice handicap index improved. In computed-tomography findings, breakage, deformation, dropped and migration of titanium plate were not identified. CONCLUSION: In surgery of vocal fold paralyzed patient, it is necessary to reconstruct vocal fold in physiological state at the time of phonation. Using the titanium plate developed for this purpose, all patients obtained good vocal improvement.

Single injection of basic fibroblast growth factor to treat severe vocal fold lesions and vocal fold paralysis.

OBJECTIVES/HYPOTHESIS: Severe vocal fold lesions such as vocal fold sulcus, scars, and atrophy induce a communication disorder due to severe hoarseness, but a treatment has not been established. Basic fibroblast growth factor (bFGF) therapies by either four-time repeated local injections or regenerative surgery for vocal fold scar and sulcus have previously been reported, and favorable outcomes have been observed. In this study, we modified bFGF therapy using a single of bFGF injection, which may potentially be used in office procedures. STUDY DESIGN: Retrospective chart review. METHODS: Five cases of vocal fold sulcus, six cases of scars, seven cases of paralysis, and 17 cases of atrophy were treated by a local injection of bFGF. The injection regimen involved injecting 50 µg of bFGF dissolved in 0.5 mL saline only once into the superficial lamina propria using a 23-gauge injection needle. Two months to 3 months after the injection, phonological outcomes were evaluated. RESULTS: The maximum phonation time (MPT), mean airflow rate, pitch range, speech fundamental frequency, jitter, and voice handicap index improved significantly after the bFGF injection. Furthermore, improvement in the MPT was significantly greater in patients with (in increasing order) vocal fold atrophy, scar, and paralysis. The improvement in the MPT among all patients was significantly correlated with age; the MPT improved more greatly in younger patients. CONCLUSIONS: Regenerative treatments by bFGF injection­even a single injection­effectively improve vocal function in vocal fold lesions. LEVEL OF EVIDENCE: 4

[The Correlation between the Size of Vocal Polyps, Vocal Nodules and Vocal Dysfunction, before and after Laryngeal Microsurgery].

When we operate on a vocal polyp or a vocal nodule with laryngeal microscopy, we always carefully measure their length and width then multiply the length by the width to get the area. We examined whether there is a correlation between the area of these lesions and the acoustic analysis of voice. Before the surgery and one month post-operation, we checked five acoustic parameters, maximum phonation time (MPT), range of voice, mean air flow rate (MFR) and acoustic analyses (jitter% and shimmer%). By doing this, we could arrive at the improvement rate of each of the five acoustic parameters. We examined whether there was a correlation between the lesion area and acoustic parameters before surgery and the improvement rates of these acoustic parameters. Examinations of polyps showed a correlation between the size and range of voice and Jitter% pre-operation, and showed a correlation between the size and improvement rate of range of voice, MFR, Jitter% and Shimmer% post-operation. On the other hand, examination of nodules showed a correlation only between the size and range of voice pre-operation. Next we examined the correlation between the size and these acoustic parameters in the Elite vocal performer (EVP) group and extra EVP group. In the examinations of polyps, the EVP group showed a lower correlation between the size and acoustic parameters than in the extra EVP group. On the other hand, in the examinations of nodules, correlation between the size and acoustic parameters was low in both the EVP and extra EVP group.

Efficient cross-presentation of soluble exogenous antigens introduced into dendritic cells using a weak-based amphiphilic peptide.

To develop a novel dendritic cell (DC)-based vaccine for inducing antigen-specific CD8+ T cell responses by cross-presentation, we tested a novel antigen delivery system that introduces soluble antigens into the cytosol of cells by an endocytosis-mediated mechanism which avoids damaging the plasma membrane ("Endo-Porter"). Proteins released from endosomes into the cytoplasm are degraded by the proteasome, and fragmented antigenic peptides are presented to the classical cytosolic MHC class I pathway. DCs pulsed with OVA protein in the presence of Endo-Porter efficiently stimulate OVA peptide-specific CD8+ T (OT-I) cells. Although this agent diverts some of the endocytosed antigens away from the classical MHC class II-restricted presentation pathway to the class I pathway, the activation of CD4+ T cells was found not to be hampered by Endo-Porter-mediated antigen delivery. On the contrary, it was rather augmented, probably due to the increased uptake of antigen. Because specific CD4+ T cell help is required to license DCs for cross-priming, Endo-Porter-mediated antigen delivery is a promising approach for developing more efficient cancer vaccines targeting both CD4+ and CD8+ T cells.

Combined insulin B:9-23 self-peptide and polyinosinic-polycytidylic acid accelerate insulitis but inhibit development of diabetes by increasing the proportion of CD4+Foxp3+ regulatory T cells in the islets in non-obese diabetic mice.

Insulin peptide B:9-23 is a major autoantigen in type 1 diabetes. Combined treatment with B:9-23 peptide and polyinosinic-polycytidylic acid (poly I:C), but neither alone, induce insulitis in normal BALB/c mice. In contrast, the combined treatment accelerated insulitis, but prevented diabetes in NOD mice. Our immunofluorescence study with anti-CD4/anti-Foxp3 revealed that the proportion of Foxp3 positive CD4(+)CD25(+) regulatory T cells (Tregs) was elevated in the islets of NOD mice treated with B:9-23 peptide and poly I:C, as compared to non-treated mice. Depletion of Tregs by anti-CD25 antibody hastened spontaneous development of diabetes in non-treated NOD mice, and abolished the protective effect of the combined treatment and conversely accelerated the onset of diabetes in the treated mice. These results indicate that poly I:C combined with B:9-23 peptide promotes infiltration of both pathogenic T cells and predominantly Tregs into the islets, thereby inhibiting progression from insulitis to overt diabetes in NOD mice.

CCL17 transgenic mice show an enhanced Th2-type response to both allergic and non-allergic stimuli.

CC chemokine ligand (CCL)17 is implicated in the pathogenesis of atopic dermatitis (AD). To study the effect of CCL17 produced by keratinocytes (KC) during inflammation, we created transgenic (Tg) mice in which CCL17 is overexpressed in KC. Th2-type contact hypersensitivity (CHS) was enhanced and Th1-type CHS was suppressed in these mice. Increased numbers of CC chemokine receptor (CCR)4(+) cells and mast cells infiltrated in Tg mice. Levels of IL-4 mRNA were higher and those of IFN-gamma mRNA were lower in both acute and chronic CHS. Higher levels of serum IgE were observed after CHS. Numbers of CCR4(+) cells among PBMC were increased in Tg mice challenged acutely on the trunk. Chronic irritation with croton oil induced dermatitis and an elevation of serum IgE levels. Tg mice showed enhanced ear swelling after tape stripping. CCL17 was thought to modify the inflammation caused by sensitizing reagents as well as irritant reagents by attracting CCR4(+) cells into the lesional skin and creating a Th2-dominant condition. AD-like conditions such as increased number of mast cells and elevated levels of serum IgE were observed. Thus, CCL17 may participate in the pathogenesis of skin diseases such as AD by regulating both allergic and irritant inflammation.

High-performance optical code generation and recognition by use of a 511-chip, 640-Gchip/s phase-shifted superstructured fiber Bragg grating.

The generation and recognition of a record-length 511-chip optical code is experimentally demonstrated by use of a superstructured fiber Bragg grating (SSFBG) with a chip rate of 640 Gchips/s. Very high reflectivity (92%) is achieved with high-quality correlation properties. The temperature deviation tolerance is approximately +/- 0.3 degrees C, which is within the package's temperature stability range (+/- 0.1 degrees C). Experimental results show good agreement with the theory. They indicate the SSFBG's potential for processing a long optical code with an ultrahigh chip rate, which could significantly improve the system's performance.

High reflectivity superstructured FBG for coherent optical code generation and recognition.

The performance of the phase-shifted superstructured fiber Bragg grating (SSFBG) for optical code (OC) recognition was investigated with different reflectivity as well as input pulse width. The auto-correlation peak (PA) and the ratios of PA to the maximum wing level (P/W) and cross-correlation level (P/C) were used to quantitatively evaluate the OC recognition performance. There is a conflict between obtaining high PA and high P/W and P/C ratios in high reflectivity regime. The approach of applying apodization technique to improve the performance in high reflectivity regime is proposed. The comparative experimental investigations with 127-chip 160-Gchip/s SSFBG are carried out to confirm the effectiveness of the proposed approach. Error-free transmission with multiplexing of two active users has been successfully achieved by the apodized SSFBG at a data rate of 1.25 Gbit/s.