Heterozygous mutation of Ush1g/Sans in mice causes early-onset progressive hearing loss, which is recovered by reconstituting the strain-specific mutation in Cdh23.

Most clinical reports have suggested that patients with congenital profound hearing loss have recessive mutations in deafness genes, whereas dominant alleles are associated with progressive hearing loss (PHL). Jackson shaker (Ush1gjs) is a mouse model of recessive deafness that exhibits congenital profound deafness caused by the homozygous mutation of Ush1g/Sans on chromosome 11. We found that C57BL/6J-Ush1gjs/+ heterozygous mice exhibited early-onset PHL (ePHL) accompanied by progressive degeneration of stereocilia in the cochlear outer hair cells. Interestingly, ePHL did not develop in mutant mice with the C3H/HeN background, thus suggesting that other genetic factors are required for ePHL development. Therefore, we performed classical genetic analyses and found that the occurrence of ePHL in Ush1gjs/+ mice was associated with an interval in chromosome 10 that contains the cadherin 23 gene (Cdh23), which is also responsible for human deafness. To confirm this mutation effect, we generated C57BL/6J-Ush1gjs/+, Cdh23c.753A/G double-heterozygous mice by using the CRISPR/Cas9-mediated Cdh23c.753A>G knock-in method. The Cdh23c.753A/G mice harbored a one-base substitution (A for G), and the homozygous A allele caused moderate hearing loss with aging. Analyses revealed the complete recovery of ePHL and stereocilia degeneration in C57BL/6J-Ush1gjs/+ mice. These results clearly show that the development of ePHL requires at least two mutant alleles of the Ush1g and Cdh23 genes. Our results also suggest that because the SANS and CDH23 proteins form a complex in the stereocilia, the interaction between these proteins may play key roles in the maintenance of stereocilia and the prevention of ePHL.

Relationship between cardiac calcification and left ventricular hypertrophy in patients with chronic kidney disease at hemodialysis initiation.

Coronary artery calcification (CAC), cardiac valve calcification (CVC) and left ventricular hypertrophy (LVH) are frequently observed in chronic kidney disease (CKD) patients. These abnormalities significantly affect morbidity and mortality. The aim of this study was to investigate the relationship between CAC, CVC and LVH in CKD patients. This study included 96 patients who were hospitalized and initiated hemodialysis between December 2011 and July 2014 at our five institutions. Multi-detector computed tomography for the quantification of CAC using the Agatston score and transthoracic echocardiography for assessing CVC and LVH were performed for all patients included in the study. We semi-quantitatively evaluated the severity of CVC as a valvular calcification score. We also assessed the presence of LVH in patients with CAC and/or CVC. Among the 96 patients, the prevalence of CAC was 81.3% and CVC was 65.0%. The severity of CAC was closely and significantly associated with that of CVC. The percentage of patients with LVH was the greatest in those with both severe CAC and CVC. CAC was significantly more severe in patients with concentric hypertrophy compared to those with normal geometry. At the initiation of hemodialysis, most CKD patients had CAC, CVC and LVH. In addition, cardiac calcification was significantly associated with LVH in these patients.

Otological complications associated with hyperbaric oxygen therapy.

The objective of the present study was to clarify the features of otological complications for hyperbaric oxygen therapy (HBOT) and the risk factors for these complications. We enrolled 1115 patients (776 males and 339 females; age 5-89 years) who underwent HBOT. All otological symptoms experienced during HBOT sessions were evaluated, and risk factors were analysed using multivariate logistic regression analysis. Otoscopic findings and interventions for otological complications were assessed in 58 symptomatic patients who visited the Otolaryngology Department. Otological symptoms were experienced by 165 (14.8 %) of the 1115 patients. The multivariate logistic regression analysis identified ages of >60 years and female sex as independent risk factors, whereas patients with sports injuries were at lower risk than those with other primary diseases, except for severe infectious disease. Eighty-two patients (49.7 %) suffered from symptoms at the first HBOT session. The most prevalent symptoms were otalgia (157/165), followed by ear fullness (13/165), hearing loss (12/165) and tinnitus (3/165). One patient experienced vertigo and deterioration of the bone-conduction pure-tone thresholds, suggesting inner ear barotrauma. In 116 ears of the 58 symptomatic patients, abnormal otoscopic findings were recognized in 58 ears (50.0 %). Twenty-seven of the 58 ears required myringotomy or tube insertion, and HBOT was stopped in eight ears in four patients. Of the remaining 58 ears with normal otoscopic findings, 51 received no treatment. Physicians should be aware of both middle and inner ear barotrauma as potential complications of HBOT.

[Otologic Manifestations in Patients with ANCA Associated Vasculitis-Comparative Analysis among Microscopic Polyangiitis, Granulomatosis with Polyangiitis and Eosinophilic Granulomatosis with Polyangiitis].

Anti-neutrophil cytoplasmic antibody (ANCA) -associated vasculitides (AAVs) include microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA), the incidences of which are reported to be increasing in Japan. We reviewed the clinical records of 20 cases with systemic AAVs (five cases with MPA, nine cases with GPA, and six cases with EGPA), who visited our otolaryngology department with otological symptoms from 2004 to 2014, and compared the otological characteristics among the diseases. Otologic symptoms appeared as an initial symptom(s) in 40% of MPA cases, 56% of GPA cases, and 83% of EGPA cases. GPA and EGPA cases showed a variety of symptoms such as otalgia, otorrhea, hearing loss, ear fullness, tinnitus and dizziness, while MPA cases showed only hearing loss and ear fullness, but otalgia or otorrhea. AAVs and otitis media associated with ANCA vasculitis (OMAAV) are usually diagnosed shortly after the appearance of otological symptoms in GPA cases, while the final diagnosis is delayed in EGPA cases. Furthermore, the diagnosis of OMAAV was made after the diagnosis of AAV in most cases of EGPA. More than half of MPA cases did not meet the diagnostic. criteria for OMAAV. It is noteworthy that in a significant number of AAV patients with ear disease, otological symptoms are supposed to appear as an initial symptom(s). Therefore, otolaryngologists have a major role to achieve early diagnosis of AAV. The patients with adult-onset inflammation of the middle ear, inner ear or both should undergo careful examinations, and they should be closely followed even if the diagnosis is uncertain.

Clinical Characteristics of Pediatric Deep Neck Abscesses.

Pediatric deep neck abscesses are a relatively rare and can lead to critical or life-threatening situations. However, the clinical characteristics of pediatric deep neck abscesses are not fully understood in Japan. We conducted a retrospective study of the clinical characteristics of children presenting with pediatric deep neck abscesses at our hospital. All pediatric patients were diagnosed with deep neck abscesses on the basis of the clinical findings and computed tomography (CT) scanning of the neck between April 2009 and March 2014. The incidence, initial examining department, sex, age, presenting signs and symptoms, physical findings, duration between onset and admission, timing of CT scanning, abscess location, causative organism, and method of treatment were determined from the medical records. 　We identified a total of 20 pediatric patients with deep neck abscesses, with a mean incidence of 4.0±1.9 cases per year. Pediatric deep neck abscesses were more common during winter and spring. Most patients initially presented to the pediatric department before consulting an otolaryngologist. Fourteen (70%) patients were male and six (30%) were female, with no obvious peak age of onset. The mean duration between onset and admission was 7.2±3.9 days. The mean timing of CT scanning was 8.1±3.6 days after onset. The most commonly involved area was the retropharyngeal space in nine (45%) and the retro-cervical space in eight (40%) patients. The most frequent causative organism was Staphylococcus aureus (20%), with no cases of antibiotic-resistant bacteria infection observed. Majority of the children were initially managed with conservative treatment. Five patients who failed to improve within 48 h of treatment subsequently underwent surgical drainage. No significant complications such as descending mediastinitis and septic shock were observed in any of the patients.

A suspected case of plasma cell-rich acute renal transplant rejection associated with de novo donor-specific antibody.

A kidney transplant case with de novo donor-specific antibody showed monoclonal plasma cell infiltration into the graft with ABO incompatibility. Three years after transplantation, the patient's graft function suddenly deteriorated. Interstitial edema and the predominant infiltration of inflammatory plasma cells with kappa chain monoclonality were observed in biopsy specimens. The in situ hybridization of Epstein-Barr virus was negative and post-transplant lymphoproliferative disorder was not evident from radiological examinations. On laboratory examination, the patient had de novo donor-specific antibody for HLA-DQ. We suspected plasma cell-rich acute rejection for which methylprednisolone pulse therapy, plasma exchange, rituximab, and 15-deoxyspergualin were given. In the ensuing biopsy, the degree of plasma cell infiltration was similar to the first biopsy; however, kappa chain monoclonality relatively weakened. Owing to resistance to these treatments, intravenous immunoglobulin (IVIG) (0.5 g/kg/day) was added. The serum creatinine level gradually declined to 3.1 mg/dL; however, it increased up to 3.6 mg/dL again. In the final biopsy, the infiltrated plasma cells disappeared but severe interstitial fibrosis developed. This case showed difficulty in the diagnosis and treatment of plasma cell-rich acute rejection. A detailed consideration of this case may be helpful in understanding the clinical features and pathogenesis of this condition.

A DFNA5 mutation identified in Japanese families with autosomal dominant hereditary hearing loss.

Mutations in DFNA5 lead to autosomal dominant nonsyndromic hereditary hearing loss (NSHHL). To date, four different mutations in DFNA5 have been reported to cause hearing loss. A 3 bp deletion mutation (c.991-15_991-13del) was identified in Chinese and Korean families with autosomal dominant NSHHL, which suggested that the 3 bp deletion mutation was derived from a single origin. In the present study, we performed genetic screening of mutations in the interval between intron 6 and exon 9 of DFNA5 in 65 Japanese patients with autosomal dominant NSHHL and identified the c.991-15_991-13del mutation in two patients. Furthermore, we compared the DFNA5-linked haplotypes consisting of intragenic SNPs between the reported Chinese and Korean families and found that the Japanese patients showed a shared region spanning 41,874 bp. This is the first report of DFNA5 mutations in Japanese patients with autosomal dominant NSHHL, supporting the suggestion that the 3 bp deletion mutation occurred in their ancestors.

The role of SLC26A4 in bony labyrinth development and otoconial mineralization in mouse models.

Inner ear malformations are predominantly attributed to developmental arrest during the embryonic stage of membranous labyrinth development. Due to the inherent difficulty in clinically assessing the status of the membranous labyrinth, these malformations are diagnosed with radiographic imaging, based on the morphological characteristics of the bony labyrinth. While extensive research has elucidated the intricacies of membranous labyrinth development in mouse models, comprehensive investigations into the developmental trajectory of the bony labyrinth, especially about its calcification process, have been notably lacking. One of the most prominent types of inner ear malformations is known as incomplete partition (IP), characterized by nearly normal external cochlear appearance but pronounced irregularities in the morphology of the modiolus and inter-scalar septa. IP type II (IP-II), also known as Mondini dysplasia, is generally accompanied by an enlargement of the vestibular aqueduct and is primarily attributed to mutations in the SLC26A4 gene. In the case of IP-II, the modiolus and inter-scalar septa of the cochlear apex are underdeveloped or missing, resulting in the manifestation of a cystic structure on radiographic imaging. In this overview, we not only explore the normal development of the bony labyrinth in mice but also present our observations on otolith mineralization. Furthermore, we investigated the specifics of bony labyrinth and otolith mineralization in Slc26a4-deficient mice, which served as an animal model for IP-II. We ensured that these findings promise to provide valuable insights for the establishment of therapeutic interventions, optimal timing, targeted sites, and preventive measures when considering the management of this condition.

High fluence in laser stapedotomy aggravates transient subjective dizziness.

BACKGROUND: Laser fenestration in stapedotomy has thermal effect to the vestibule. AIMS/OBJECTIVES: To evaluate the role of energy density (fluence) in the severity of postoperative vestibular symptoms. MATERIALS AND METHODS: The retrospective chart-review study included 84 patients with otosclerosis that underwent primary laser stapedotomy. Surgical outcomes, including nystagmus, and subjective vestibular symptoms during one-month follow-up, were compared between potassium titanyl phosphate (KTP) and CO2 laser. According to this study and literature, we assessed the relationship between laser parameters and the incidence of persistent vestibular symptoms lasting more than one week after surgery. RESULTS: The KTP and CO2 laser group included 48 and 36 patients, respectively. Fluence was different between the KTP (637 J/cm2) and CO2 (141 J/cm2) laser (p < .001). The KTP group showed gradual decrease in dizziness during one-month observation period, while the CO2 group exhibited a steep recovery curve in the first postoperative week (9 and 4 d of duration, respectively). The incidence of persistent vestibular symptoms was correlated with both fluence (r = 0.80, p = .01) and spot size (r = -0.74, p = .01). CONCLUSIONS AND SIGNIFICANCE: Appropriate setting of parameters with lower fluence is desirable for the efficiency and safety of laser stapedotomy.Abbreviations: ABG: air-bone gap; SD: standard deviation.

Association between AST-120 and abdominal aortic calcification in predialysis patients with chronic kidney disease.

BACKGROUND: Vascular calcification is associated with mortality and cardiovascular events in patients with chronic kidney disease. AST-120, which adsorbs uremic toxins, is reported to reduce the risk of cardiovascular disease and death in chronic kidney disease patients. The aim of the current study was to investigate the association between abdominal aortic calcification and the use of AST-120 in predialysis chronic kidney disease patients. METHODS: A retrospective analysis was conducted including 199 predialysis chronic kidney disease patients (stages 4 and 5) who underwent abdominal plain computed tomography in our institution between 2005 and 2010. Abdominal aortic calcification was assessed by aortic calcification index (ACI). Patients were divided into two groups based on whether or not AST-120 was administered for at least six months, and ACI was compared between the two groups. RESULTS: The aortic calcification index was significantly lower in patients taking AST-120 [12.2 (2.5-30.3) vs. 25.7 (13.4-45.3) %, P < 0.001]. According to multivariate linear regression analysis, the use of AST-120 was independently and significantly correlated with ACI after adjusting for confounding factors. CONCLUSIONS: The use of AST-120 was independently associated with less aortic calcification in predialysis chronic kidney disease patients.

Extended screening for major mitochondrial DNA point mutations in patients with hereditary hearing loss.

Hearing loss (HL) is the most common sensory disorder in humans. Many patients with mitochondrial diseases have sensorineural HL (SNHL). The HL of these patients manifests as a consequence of either syndromic or nonsyndromic mitochondrial diseases. Furthermore, the phenotypes vary among patients even if they are carrying the same mutation. Therefore, these features make it necessary to analyze every presumed mutation in patients with hereditary HL, but the extensive analysis of various mutations is laborious. We analyzed 373 patients with suspected hereditary HL by using an extended suspension-array screening system for major mitochondrial DNA (mtDNA) mutations, which can detect 32 other mtDNA mutations in addition to the previously analyzed 29 mutations. In the present study, we detected 2 different mtDNA mutations among these 373 patients; m.7444G>A in the MT-CO1 gene and m.7472insC in the MT-TS1 gene in 1 patient (0.3%) for each. As these two patients had no clinical features other than HL, they had not been suspected of having mtDNA mutations. This extended screening system together with the previous one is useful for the genetic diagnosis and epidemiological study of both syndromic and nonsyndromic HL.

[Intralabyrinthine schwannoma extending into the round window niche and internal auditory canal].

Intralabyrinthine schwannomas (ILSs) are rare benign neoplasms arising from distal branches of the cochlear, superior vestibular, or inferior vestibular nerves. We report on a case of ILS with extensions to the round window niche and internal auditory canal (IAC) in a 47-year-old male. The patient noticed sudden hearing loss and tinnitus in his left ear at the age of 36, received steroid therapies, but was left with complete deafness. He had suffered from repetitive vertigo attacks for 6 months at 41. At 46 when he presented with deterioration of his left tinnitus, he was finally diagnosed as having ILS on enhanced MRI and constructive interference in steady-state analysis. The tumor was located in all turns of cochlea, vestibule, and the fundus of the IAC. Because follow-up MRI suggested growth of the IAC tumor, we performed total removal of the tumor via the translabyrinthine and transcanal approaches. The tumor had invaded only the cochlear nerve in the IAC and appeared in the round window niche in the middle ear. Pathological examination showed an Antoni A type schwannoma with fibrous changes of the semicircular canals. We should remember this inner

[Case of acute pharyngitis caused by Corynebacterium ulcerans in Ibaraki Prefecture].

We report on the case of a 51-year-old woman who presented with refractory pharyngitis caused by toxigenic Corynebacteriumn ulcerans (C. ulcerans). Thick pseudomembrane formations and yellowish pus were observed in her nasopharynx. Based on her clinical course and history of breeding cats, we considered C. ulcerans infection as the possible diagnosis. She was treated with macrolide administration and her symptoms immediately improved. C. ulcerans was identified in pus from the patient's pharynx as well as in discharge material from her cat's eyes, and C. ulcerans was thought to have caused her pharyngitis. C. ulcerans is one of the infecting bacteria which can cause a zoonotic infection. In Japan, some cases with C. ulcerans infection from cats have been reported. It is important that we should consider C. ulcerans infection as a differential diagnosis of refractory pharyngitis.

[Thiel's method of embalming and its usefulness in surgical assessments].

When we assess anatomical problems and the safety and effectiveness for performing a difficult surgical procedure or planning novel surgical approaches, preoperative human dissections are very helpful. However, embalming with the conventional formaldehyde method makes the soft tissue of the cadaver harder than that of a living body. Therefore, the cadaver embalmed with conventional formaldehyde is not appropriate for dissections when assess surgical approaches. Thiel's method is a novel embalming technique, first reported by W. Theil in 1992. This method can preserve color and softness of the cadaver without risk of infections. We have used cadavers embalmed with Thiel's method for preoperative assessments and have confirmed the usefulness of this method especially for the prevention of complications or in assessing surgical approaches. The cadaver embalmed with this method has several advantages over other embalming methods and it might be also useful for the developments of new surgical devices or evaluation of a surgeon's skill.

[Audiological analysis and peri-and postoperative complications in bone-anchored hearing aid surgery].

The bone-anchored hearing aid (BAHA) has advantages over conventional hearing aids in sound quality and speech reception in silence, but requires surgery and may have peri-and postoperative complications. We evaluated audiological findings and complications in 12 subjects (13 ears)-8 men and 4 women aged 20-71--undergoing BAHA surgery from September 2001 to October 2005. Surgery was for single-sided deafness in one subject. Mean warble tone thresholds with BAHA were 29.9dB and 65.2dB without. Functional gains ranged from 16 to 52dB (mean: 35.3dB). Dural exposure or venous hemorrhage was seen in 4 ears, and mastoid cells opened and a skin flap was damaged in 1 ear each. No severe complications occurred perioperatively. Skin reactions categorized into grade 1 or more were recognized in nearly 70% of ears during the first postoperative year but most were a grade 1 reaction and skin reactions decreased with time. Skin overgrowth occurred in 1 ear immediately after an abutment separated accidentally from the fixture. All complications were treated in outpatient clinics. No fixture extrusion occurred. The decision to proceed with BAHA surgery thus required fully informed consent based on knowledge of peri-and postoperative complications.

[Multicenter clinical study of bone-anchored hearing aids in Japan--application for congenital auricular atresia].

The effectiveness of bone anchored hearing aid (BAHA) for the patients with congenital aural atresia was evaluated by multicenter clinical study in Japan. Twenty patients (17 bilateral and 3 hemilateral) of congenital auricular atresia were registered for this study and finally, 18 of them (15 bilateral and 3 unilateral) were subjected to further evaluation. Primary endpoint of this study was free sound-field pure-tone audiometory and speech threshold hearing test in quiet and noisy circumstances. Secondary endpoint of this study was patient's satisfaction based upon APHAB (Abbreviated Profile of Hearing Aid Benefit) questionnaire survey. These results were compared between before and 12 weeks after BAHA surgery. Both hearing level of pure tone and speech threshold significantly improved after BAHA surgery. APHAB scores also suggested the improvement of the QOL after BAHA usage, except for the scores that concerned with unpleasantness of noisy sound. BAHA is one of the useful options for the treatment of congenital auricular atresia.

Extensive and rapid screening for major mitochondrial DNA point mutations in patients with hereditary hearing loss.

Sensorineural hearing loss (HL) is one of the most frequent clinical features in patients with mitochondrial diseases caused by mitochondrial DNA (mtDNA) mutations, and hearing is impaired in over half of all cases with mitochondrial disorders. This study analyzed 373 patients with suspected hereditary HL using an extensive and rapid suspension-array screening system for 29 major mtDNA mutations, including the m.1555A>G homoplasmic mutation in the MT-RNR1 gene, which causes non-syndromic sensorineural HL and aminoglycoside-induced HL, and the m.3243A>G heteroplasmic mutation in the MT-TL1 gene. This method is rapid and suitable for large-scale screening because universal 96-well plates are available for use, and because an analysis of each plate can be completed within 1 h. This system detected five different mtDNA mutations in 24 of the 373 (6.4%) patients. The m.1555A>G and m.3243A>G mutations were detected in 11 (2.9%) and 9 (2.7%) patients, respectively. In addition, three mutations, that is, m.8348A>G in the MT-TK gene, m.11778G>A in the MT-ND4 gene and 15498G>A in the MT-CYB gene were detected in one patient for each. This screening system is useful for the genetic diagnosis and epidemiological study of both syndromic and non-syndromic HL.

Clinical prognostic factors for tinnitus retraining therapy with a sound generator in tinnitus patients.

OBJECTIVES: The purpose of the present study is to find out the clinical characteristics which determine candidates for tinnitus retraining therapy (TRT) with a sound generator (SG) as well as the prognosis of this treatment. METHOD: This study enrolled 270 serious tinnitus patients who visited this institute between January 2004 and December 2008 in the TRT program. The relationships among compliance, efficacy, clinical characteristics, and affinity for SG were evaluated retrospectively. RESULTS: The persistence rate at one month was 61.5%. The shorter duration and higher pitch of tinnitus were significant independent predictors of compliance. Six months after the initiation of TRT, 65.2% subjects demonstrated significant relief from tinnitus. The Kaplan-Meier method demonstrated that the overall efficacy rate at 18 months was 86.5%. The lower loudness of tinnitus, recognition of tinnitus attenuation by a sound generator, and patient's positive attitude toward TRT were significant variables for predicting favorable results. CONCLUSION: The patients with lower loudness of tinnitus were suitable for TRT with a SG.

Secondary hyperbaric oxygen therapy for idiopathic sudden sensorineural hearing loss in the subacute and chronic phases.

This study investigated the efficacy of hyperbaric oxygen therapy (HBOT) as a secondary treatment for patients with idiopathic sudden sensorineural hearing loss (ISSNHL) in the subacute and chronic phases. Forty-eight ISSNHL patients (HBOT group) who had received primary conventional treatment within 4 weeks after onset and underwent HBOT between 4 and 20 weeks post-onset were retrospectively compared with 44 ISSNHL patients (control group) with primary conventional treatment alone. Mean hearing gain was slight, with gains of 5.2 +/- 8.9 dB in the HBOT group and 2.0 +/- 7.6 dB in the control group. However, no significant difference was recognized between the two groups. In the HBOT group, no significant difference was observed in hearing gain among patients with HBOT initial time at 4-7, 8-11, 12-15 or 16-20 weeks after onset. Meanwhile, hearing gain was significantly higher in patients with profound hearing loss than in the other patients. We conclude that the effectiveness of secondary HBOT for ISSNHL patients in either subacute or chronic phase remains unproven, and thus, the decision administer HBOT should be made with caution.

A 24-month-follow-up study of argon plasma coagulation of the inferior turbinate in patients with perennial nasal allergy.

We report a 24-month-follow-up study of argon plasma coagulation of the inferior turbinate (APC) in patients with perennial nasal allergy. This was a retrospective study, in which 41 patients with perennial allergic rhinitis were treated by inferior turbinate reduction using APC. The grades of nasal stuffiness, rhinorrhea, sneezing and the daily activity impairment caused by these nasal symptoms were evaluated before and then 6, 9, 12, 15, 18, 21, and 24 months after APC, using a questionnaire graded on a four-point scale according to the Severity Criteria of Symptoms of Nasal Allergy issued by the Japanese Society of Allergology. Both nasal stuffiness and any daily activity impairment significantly improved 6 months after APC. Twenty four months after APC, 8/10 (80%) of the patients reported mild or no stuffiness and 9/10 (90%) of the patients reported mild or no daily activity impairement. Neither rhinorrhea nor sneezing were significantly improved during this study. Of the 41 patients 18 (43.9%) received no additional treatment. A second APC treatment was administered to 10/41 (24.4%) patients during follow-up period. Additional conservative medications were needed in 15/41 (36.6%) patients. Among the patients uncontrolled by conservative medical treatment, inferior turbinate reduction using APC provides significant relief in a 24-month-follow-up from nasal stuffiness and daily activity impairment.