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No clinically useful prognostic factors have been identified for idiopathic sudden sensorineural hearing loss (ISSNHL). The current study therefore sought to identify useful prognostic factors for idiopathic sudden sensorineural hearing loss from blood biomarkers while attempting to classify the pathogenic mechanism and formulate treatment strategies based on these results.Prospective cohort study.Tertiary referral center.A total of 47 patients with acute phase ISSNHL were treated with steroid at an initial dose of 1 mg/kg/day and hyperbaric oxygen therapy and followed up for 6 months. Serum fibrinogen levels, peripheral blood mononu- clear cells (PBMCs), and interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α production levels from PBMCs were measured, after which patient's pre- and post- treatment hearing was compared.In the overall cohort, the mean improvement level, mean recovery rate, and mean fibrinogen level was 20.3 dB, 46.2%, 292.0 mg/mL, respectively. The mean levels of IL-1β, IL-6, and TNF-α produced by peripheral blood mononu- clear cells cultured under lipopolysaccharide stimulation were 318.4, 498.1, and 857.6 pg/mL, respectively. High fibrinogen levels were associated with poor hearing progno- sis. Lipopolysaccharide-stimulated cytokine production by PBMCs did not correlate with hearing changes; however, the prognosis was significantly better in patients with low fibrinogen levels and high IL-1β levels produced by PBMCs than in other patients.Our results suggest that patients with simple inflammatory-type ISSNHL responded well to standard therapy. Therefore, serum fibrinogen levels and PBMCs cytokine production may help determine the management of ISSNHL based on its pathogenic mechanism.

Pierre-Robin sequence (PRS) is a rare, congenital defect presenting with micrognathia, glossoptosis, and airway obstruction with variable inclusion of a cleft palate. Overlapping PRS with neurofibromatosis type 2 (NF2) is a syndrome caused by a chromosome 22q12 microdeletion including NF2. We describe a patient with severe early-onset NF2 overlapping with PRS that showed micrognathia, glossoptosis, and a mild form of cleft palate. We detected a de novo chromosome 22q12 microdeletion including MN1 and NF2 in the patient. Previous cases of overlapping PRS and NF2 caused by the chromosome 22q12 microdeletions showed severe NF2 phenotypes with variable severity of cleft palate and microdeletions of varying sizes. Genotype-phenotype correlations and comparison of the size and breakpoint of microdeletions suggest that some modifier genes distal to MN1 and NF2 might be linked to the cleft palate severity.

Objective Cancer cells secrete large amounts of lactic acid via aerobic glycolysis. We have shown that lactic acid plays an important role as a proinflammatory and immunosuppressive mediator and promotes tumor progression. Fluorine-18 fluorodeoxyglucose (FDG) uptake detected by positron emission tomography/computed tomography (PET/CT) is considered as a good indicator of aerobic glycolysis in cancer. In this study, we examined the relationships between systemic inflammatory parameters and FDG-PET/CT parameters in advanced head and neck squamous cell carcinoma (HNSCC). Furthermore, we investigated the relationships between FDG-PET/CT parameters and M2-macrophage polarization in HNSCC by assessing the ratio of CD163, a M2-macrophage marker, to CD68, a pan-macrophage marker. Methods This study included 73 advanced HNSCC patients. We assessed the C-reactive protein (CRP) level, white blood cell (WBC) count, neutrophil count, lymphocyte count, and monocyte count as systemic inflammatory markers. Additionally, we assessed the maximum standardized uptake value (SUVmax), mean SUV (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) as FDG-PET/CT parameters. Results The CRP level, WBC count, and neutrophil count were correlated with whole-body FDG-PET/CT parameters. The CD163/CD68 ratio was correlated with SUVmax and SUVmean. Our results suggest that systemic inflammation, which is associated with neutrophils, develops in patients with HNSCC having tumors with a larger volume and increased glucose uptake and that M2-macrophage polarization is promoted in HNSCC with increased glucose uptake, SUVmax, and SUVmean. FDG-PET/CT has the potential to reflect cancer-related chronic inflammation and immunosuppressive conditions in cancer patients. Conclusions FDG-PET/CT parameters appear to be useful in assessing the immune status in HNSCC.

Objectives The efficacy of intratympanic steroid (ITS) injection for intractable Meniere's disease has been reported; however, its differences in responsiveness are not fully understood. This study investigated the clinical characteristics of patients who responded to ITS injection treatment. Methods This retrospective study included 32 patients with Meniere's disease who were unable to control frequent vertigo attacks despite conservative treatment for at least 3 months. They received an intratympanic injection of dexamethasone (3.3 mg/mL) in the affected side at least three times. We measured hearing threshold, subjective symptom scores, cervical and ocular vestibular evoked myogenic potential (cVEMP and oVEMP), and performed glycerol and bithermal caloric tests. Results Satisfactory control of vertigo for 1 year after the first round of injection was found in 18 patients (56.3%; the response group). However, the injections failed to control vertigo in the other 14 patients (43.8%; the non-response group), and they were then treated with middle ear micropressure therapy. The response group showed improvement in low-frequency hearing, whereas hearing acuity did not change in the non-response group. Significantly reduced amplitude of cVEMP on the affected side was found in 62.5% of patients in the response group; however, no patients in the non-response group showed reduced amplitude of cVEMP. Conclusions ITS injection significantly improved the subjective symptoms for intractable Meniere's disease; however, the long-term effects were heterogeneous. Our results suggest that reduced amplitude in cVEMP is associated with the effectiveness of ITS injection treatment.

An open penetrating external laryngotracheal injury (PE-LTI) is a rare life-threatening injury requiring immediate intervention. Penetrating injuries may cause tissue loss, which makes wound closure difficult sometimes. Here, we report the case of an open PE-LTI and abdominal trauma by suicide attempt. A 38-year-old Asian man with depression was found in his home after having cut his own neck and abdomen. He was transported to a regional trauma center and immediately intubated. On arrival, his blood pressure was 120/90 mmHg and heart rate was 120 beats/min. Physical examination revealed three cuts each on the neck and abdomen and no dysphonia. The patient's condition was diagnosed as an open PE-LTI, classified as group 5 on the Schaefer classification system and zone II on the Roon and Christensen classification system. He was also evaluated for possible mesenteric injury. We performed an emergency primary laryngotracheal repair and exploratory laparotomy. There was no obvious blood vessel injury, but soft and cartilage tissues were crushed and disconnected completely. On day 8, he underwent wound closure and tracheostomy on the caudal side of the wound. He was successfully weaned from mechanical ventilation on day 9, transferred to the general ward on day 13, decannulated on day 63, and discharged from the hospital thereafter for subacute care. In this case of severe neck injury with complete laryngotracheal separation, tissue losses were relatively minimal. Wound closure presumably occurred early in the absence of blood vessel injury., Highlights • We could close wounds of external laryngotracheal injury early because despite complete laryngotracheal separation, the sharp and horizontal lacerations by suicide attempt with a kitchen knife were not accompanied by significant tissue losses. • Although jugular vein or vertebral artery injuries are common with neck trauma, the findings from our case indicate that early wound closure may occur in case of an open penetrating external LTI without blood vessel injuries. • We think there is a need for a new classification system that considers the sharpness of the wound, the degree of tissue loss and disruption, and the nature of the object that causes the injury.

Background: An open penetrating external laryngotracheal injury (LTI) is a rare life-threatening injury requiring immediate intervention. Penetrating injuries may cause tissue loss, which makes wound closure difficult sometimes. Here, we report the case of a patient who developed an open penetrating external LTI and abdominal trauma by suicide attempt, which required surgical intervention.Case presentation: A 38-year-old Asian man with depression was found lying on the floor after cutting his neck and abdomen by himself. The emergency services found multiple deep lacerations on his anterior neck and abdomen. He was brought by a helicopter with a physician onboard to a regional trauma center and immediately intubated at the emergency department to secure his airway and prevent airway obstruction. On arrival, his blood pressure was 120/90 mmHg, and his heart rate was 120 beats/min. A pre-shock status was presumed, but other vital signs were normal. Physical examination revealed cut wounds (three lines on the neck and two lines on the abdomen) and no dysphonia. The patient was diagnosed with an open penetrating external LTI, classified as group 5 on the Schaefer classification system and zone Ⅱ on Roon and Christensen’s modification. He was also suspected with a mesenteric injury. We performed an emergency primary laryngotracheal repair and exploratory laparotomy. There was no obvious blood vessel injury, but soft and cartilage tissues were crushed and disconnected completely. On day 8, he underwent wound closure and tracheostomy on the caudal side of the wound. He was successfully weaned from mechanical ventilation on day 9, transferred to the general ward on day 13, decannulated on day 63, and discharged from the hospital thereafter for subacute care.Conclusions: This case was a severe neck injury with complete laryngotracheal separation, but tissue losses due to knife-stabbing were relatively minimal. Wound closure was presumed to occur early during primary repair, even though the purpose of primary repair was originally to secure the airway or manage blood vessel injury. Thus, in the absence of blood vessel injury, wound closure may occur early in patients who developed an open penetrating external LTI by suicide attempt.

Background Biphenotypic sinonasal sarcoma (BSNS) is a rare sarcoma with neural and myogenic pathological features. Histopathologically, BSNS has been regarded as a low-malignant tumor with favorable prognosis. Herein, we report a case of BSNS with a seemingly high-grade malignancy and an extremely acute exacerbation. Case description A 64-year-old woman was diagnosed with BSNS and underwent surgical extraction of a tumor twice. Two months later after the second operation, recurrence occurred, with intracranial tumor extension as well as infiltrations around the carotid artery. Two cycles of chemotherapy with doxorubicin and ifosfamide were administered, which significantly reduced the tumor volume. Subsequently, a treatment with oral pazopanib was administered. No tumor progression was observed in the next 2 and a half months, followed by local progression. Discussion Our case seems to be entirely different from those described in previous reports on BSNS and should be regarded clinically as an extremely high malignant tumor. This high malignancy involved the high proliferative activity and invasiveness of critical organs such as in the intracranial area. AI therapy consisted of a regimen with doxorubicin and ifosfamide showed anti-tumor effects, as well as a temporary inhibition of tumor progression was achieved with pazopanib. Conclusion AI therapy and pazopanib might be considered as a potential postoperative adjuvant therapy and second-line therapy for severe BSNS.

The present study aimed to assess CT and MR imaging findings of infection-free and benign second branchial cleft cysts (SBCCs). Eleven patients with histopathologically confirmed infection-free and benign SBCCs underwent preoperative contrast-enhanced CT (CECT) and/or MR imaging. We assessed qualitative (presence and extent of wall thickening, degree of contrast enhancement of the thickened wall on CECT images, and signal intensity of the thickened wall on T2-weighted images) and quantitative (maximum thickness of the thickened wall) imaging findings. Eccentric and smooth wall thickening was observed in 11/11 (100%) patients. The wall thickening extent (percentage of the thickened wall to the circumference of the wall) was small (1%–25%) in 4/11 (36%), moderate (26%–50%) in 6/11 (54%), extensive (51%–75%) in 1/11 (9%), and diffuse (76%–100%) in 0/11 (0%) patients. Mild homogeneous enhancement of the thickened wall on CECT images was observed in 7/7 (100%) patients. The signal intensity of the thickened wall on T2-weighted images was isointense relative to that of normal lymph nodes in 7/8 (88%) and mildly hyperintense in 1/8 (12%) patient. The maximum thickness of the thickened walls ranged from 2 to 4 (mean 3.4) mm. Infection-free and benign SBCCs are identifiable as cysts with eccentric and smooth wall thickening on CECT and MR images. The wall thickness was almost always less than half of the wall circumference, isointense relative to normal lymph nodes, and showed mild homogeneous enhancement.

Reprogramming of glucose metabolism in tumor cells is referred to as the Warburg effect and results in increased lactic acid secretion into the tumor microenvironment. We have previously shown that lactic acid has important roles as a pro‐inflammatory and immunosuppressive mediator and promotes tumor progression. In this study, we examined the relationship between the lactic acid concentration and expression of LDHA and GLUT1, which are related to the Warburg effect, in human head and neck squamous cell carcinoma (HNSCC). Tumors expressing lower levels of LDHA and GLUT1 had a higher concentration of lactic acid than those with higher LDHA and GLUT1 expression. Lactic acid also suppressed the expression of LDHA and GLUT1 in vitro. We previously reported that lactic acid enhances expression of an M2 macrophage marker, ARG1, in murine macrophages. Therefore, we investigated the relationship between the lactic acid concentration and polarization of M2 macrophages in HNSCC by measuring the expression of M2 macrophage markers, CSF1R and CD163, normalized using a pan‐macrophage marker, CD68. Tumors with lower levels of CD68 showed a higher concentration of lactic acid, whereas those with higher levels of CSF1R showed a significantly higher concentration of lactic acid. A similar tendency was observed for CD163. These results suggest that tumor‐secreted lactic acid is linked to the reduction of macrophages in tumors and promotes induction of M2‐like macrophage polarization in human HNSCC.

Purpose: To evaluate the significance of additional coronal reconstruction images in the diagnostic ability of contrastenhanced computed tomography (CECT) for metastatic cervical nodes in patients with head and neck squamous cell carcinomas (HNSCC). Material and methods: We retrospectively assessed 97 metastatic and 141 reactive histologically proven cervical nodes of 38 patients with HNSCC, who underwent CECT before neck dissection. Observer #1, an expert radiologist in head and neck imaging, and observer #2, a general radiologist, reviewed all CECT images. The observers first assessed the presence of nodal metastasis using axial CECT alone (A-CECT). Three days later, they reassessed its presence using combined axial and coronal CECT (A&C-CECT). Results: The sensitivity of A-CECT vs. A&C-CECT was 73.2% vs. 75.3% for observer #1 (p = 0.73) and 69.1% vs. 69.1% for observer #2 (p = 1.00), respectively. The specificity of A-CECT versus A&C-CECT was 92.2% vs. 97.2% for observer #1 (p < 0.05) and 92.9% vs. 95.7% for observer #2 (p = 0.22), respectively. The accuracy of A-CECT versus A&C-CECT was 84.5% vs. 88.2% for observer #1 (p < 0.05) and 83.2% vs. 85.3% for observer #2 (p = 0.30), respectively. The area under the curve (AUC) of A-CECT vs. A&C-CECT was 0.86 vs. 0.91 for observer #1 (p < 0.05) and 0.85 vs. 0.85 for observer #2 (p = 0.80), respectively. Conclusions: The specificity, accuracy, and AUC increased with the use of coronal images during the assessment by the expert radiologist. The appropriate use of coronal images allowed proper configuration recognition and improved diagnostic ability.

Hearing loss (HL) has been recognised as a prodromal symptom of cognitive disorder with aging. It is still uncertain if HL leads to cognitive impairment directly or through an indirect mechanism. Participants of this study underwent an auditory test, blood tests, and brain MRI. The atrophy rate of the hippocampus (HP) was calculated using voxel-based specific areas. A partial correlation analysis whilst controlling for the effect of age was performed to analyse the factors affecting hearing levels and HP atrophy rate (HP%). Thirty-six older adults with hearing impairment The group of participants with moderate or severe HL (n = 22) had higher cortisol/dehydroepiandrosterone sulphate (C/D) ratio, geriatric depression score (GDS) and HP% than the mild HL or normal hearing group (n = 14, p p p Our results suggest that the HL is associated with the atrophy of HP and high C/D ratios in older adults; however, HL may not be causally related to hippocampal atrophy.

Muckle-Wells syndrome (MWS), a subclass of cryopyrin-associated periodic syndrome (CAPS), sometimes includes complications of bilateral progressive sensorineural hearing loss. A 48-year-old woman had been diagnosed with pediatric rheumatic arthritis at aged 6 years; however, systematic therapy with prednisolone and methotrexate showed limited efficacy for her general fatigue and arthritic pain, and it never improved the hearing level. She underwent a cochlear implant surgery for progressive profound bilateral hearing loss. After 7 years of cochlear implant surgery, she was diagnosed with MWS by genetic tests. Interleukin (IL)-1β monoclonal antibody therapy (canakinumab) improved general fatigue and arthritic pain but showed no effect on cochlear symptoms. Owing to successful cochlear implant surgery, she reacquired the hearing and communication function while being able to understand over 90% of monosyllables and words in the sound field of her daily life at 65 dB SPL for the next 13 years of her life. This suggests that peripheral cochlear damage induced by chronic inflammation contributes to the sensorineural hearing loss in cases with MWS, and that cochlear implantation can provide long-term hearing efficacy for patients with MWS with irreversible profound hearing loss.

A variety of neoplastic and non-neoplastic lesions of the parotid gland can present with a predominantly cystic architecture, and although radiologists frequently encounter cystic parotid tumors, other non-neoplastic lesions should also be included in the differential diagnoses of cystic parotid lesions. Non-neoplastic cystic lesions are usually classified as either congenital/acquired cystic lesions or inflammatory/infectious lesions. Adequate knowledge about these rare conditions is essential for appropriate diagnosis and optimal treatment strategy. This review article describes CT and MR imaging features of non-neoplastic cystic lesions of the parotid gland and provides helpful suggestions on the differential diagnoses for cystic parotid lesions.

Objective:This study aimed to assess the imaging features and natural course of clavicle fracture following neck dissection (ND).Methods and materials:Eight patients with clavicle fracture following ND were included. Because bilateral clavicle fractures occurred in one patient, a total of nine clavicle fractures following ND were assessed using CT images. Pathological fracture due to bone metastasis or local recurrence was carefully ruled out.Results:The time interval from ND to clavicle fracture ranged from 2 to 8 months (median, 4 months). On CT images, all the nine fractures occurred in the proximal clavicles and displayed increased bone marrow density with extraosseous soft-tissue mass formation. Osteolysis of the clavicle was not observed. Intra articular fractures were observed in three (33%), displaced fractures in two (22%), and free bone fragments in three (33%) cases. Further follow-up using CT showed that six (67%) fractures resulted in pseudoarthrosis. For the remaining three (33%) fractures with bone union during follow-up, the time interval between clavicle fracture and bone union ranged from 4 to 16 months (median, 6 months).Conclusion:Proximal clavicle fractures, which are rarely observed following ND, always display extraosseous soft-tissue mass formation without osteolysis. They frequently result in pseudoarthrosis; however, occasionally, they also result in bone union within 24 weeks.Advances in knowledge:The location of proximal clavicle, the lack of osteolysis, and the presence of free bone fragments may be the key to diagnosis of clavicle fracture following ND.

Small cell neuroendocrine carcinoma of the head and neck is a rarely occurring poorly differentiated and high-grade malignant neoplasm characterized by highly active proliferation of neuroendocrine tumor cells. There are no established therapies for this disease. To clarify the clinical course and develop effective treatment(s) for the carcinoma, we reviewed the data of 8 patients of small cell neuroendocrine carcinoma of the head and neck treated by us between 2006 and 2014 at the Department of Otolaryngology, Gifu University School of Medicine and our affiliated hospitals. The patients consisted of 3 men and 5 women, ranging in age from 38 to 84 years old (mean : 60.9 years). The tumor arose from the nasal cavity or the paranasal sinuses in 3 cases, from the parotid grand in 2 cases, from the oropharynx in 2 cases, and from the hypopharynx in 1 case. The tumor that arose from the hypopharynx was a combined small-cell carcinoma with squamous cell carcinomas, and the one that arose from the oropharynx had already metastasized to the brain. Most of the patients were treated by chemotherapy and radiotherapy based on the treatment employed for small cell carcinoma of the lung. Only the patient in whom the tumor arose from a paranasal sinus was treated by surgery despite the definitive diagnosis of small cell carcinoma. We selected CPT-11 and a platinum agent for 4 patients, and VP-16 and a platinum agent for 3 patients as the first-line chemotherapy. Although two patients showed carcinoma-free survival, one died of recurrence of the regional lymph node metastases and five died of distant metastases despite the absence of locoregional recurrence. The 5-year survival rate was a dismal 25%, suggesting that we need to establish effective treatment(s) for the control of distant metastases in cases of the small cell neuroendocrine carcinoma of the head and neck.

Background The purpose of the present study was to determine whether polaprezinc suspension in sodium alginate (P-AG) reduces the irradiation period and time to discharge after completion of radiotherapy in patients with head and neck cancer. Methods The incidence and severity of oral mucositis, the irradiation period, and the time to discharge in patients who received radiotherapy with head and neck cancer were investigated retrospectively from the medical records. Results The incidence of grade 3 oral mucositis was significantly lower in the P-AG group than in the control group (16.5% vs 52.0%; p = .0003). P-AG also significantly reduced median duration of radiotherapy (hazard ratio [HR] = 0.557; 95% confidence interval [CI] = 0.357–0.871; p = .0149) and median time to discharge after completion of radiotherapy (HR = 0.604; 95% CI = 0.386–0.946; p = .028). Conclusion P-AG reduced the irradiation period and the time to discharge after completion of radiotherapy by preventing oral mucositis in patients with head and neck cancer. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

The faithful shutdown of the somatic program occurs in the early stage of reprogramming. Here, we examined the effect of in vivo reprogramming on Kras-induced cancer development. We show that the transient expression of reprogramming factors (1–3 days) in pancreatic acinar cells results in the transient repression of acinar cell enhancers, which are similarly observed in pancreatitis. We next demonstrate that Kras and p53 mutations are insufficient to induce ERK signaling in the pancreas. Notably, the transient expression of reprogramming factors in Kras mutant mice is sufficient to induce the robust and persistent activation of ERK signaling in acinar cells and rapid formation of pancreatic ductal adenocarcinoma. In contrast, the forced expression of acinar cell-related transcription factors inhibits the pancreatitis-induced activation of ERK signaling and development of precancerous lesions in Kras-mutated acinar cells. These results underscore a crucial role of dedifferentiation-associated epigenetic regulations in the initiation of pancreatic cancers., Cellular reprogramming and cancer development share properties. Here, the authors examine the impact of in vivo reprogramming on Kras-induced cancer and show reprogramming-mediated repression of somatic cell enhancers in conjunction with Kras mutation results in rapid PDAC development.

Gorham-Stout disease (GSD) is a rare disorder of unknown etiology. We present a 6-year-old male with GSD involving the skull base who presented with recurrent cerebrospinal fluid (CSF) rhinorrhea, severe hearing loss, and facial palsy secondary to cerebellar herniation into the internal auditory canal. After 2 months of treatment with pegylated interferon (IFN) α-2b (50 μg/week), his hearing recovered dramatically. Two years later, new bone formation appeared radiologically and IFN was switched to sirolimus. One year after the switch, CSF rhinorrhea disappeared. Antiangiogenic therapy might inhibit proliferation of vascular endothelial cells in osteolytic lesions and lead to new bone formation.

The statistical properties of the center of pressure (COP) change over time, and -invariant methods of the COP analysis is not sufficient to monitor the changes. Therefore, dynamic temporal information of the COP signals has been important in assessing the postural stability. The purpose of this study was to evaluate the characteristic pattern of time-frequency dynamics during the upright stance in patients with unilateral vestibular dysfunction (UVD). This study included 20 dizzy patients with UVD and age-matched 20 control subjects without any vestibular disorder. The COP signals were collected using a single standard force platform and a spectral analysis including the time-frequency dynamics was carried out on the basis of the maximum entropy method (MEM) by using a segment time series analysis. The power spectral density (PSD) analysis exhibited an exponential decreasing shape (1/f (-)(β)) when plotted on a double logarithmic scale. The average value of β in the low frequency range of less than 1 Hz in the UVD group was significantly lower than that in the control group (p < 0.05) in the medial-lateral (ML) direction under eyes closed condition. In the segment time series analysis, the peak frequency of the COP signals in the patients with UVD gradually converged to the frequency range of 0.1-0.2 Hz in the ML direction under EC condition. Our results suggest that the segment time series analysis of the COP signals can derive a characteristic pattern related to the UVD. It may indicate an increased reflexivity of the COP fluctuation by the UVD, resulting in inducing the instability.

Bleeding from parathyroid cysts is rare. The retropharyngeal space has a very soft structure and if bleeding spreads to this space, airway obstruction can easily occur. We report on a 50-year-old female case with idiopathic neck bleeding from a left parathyroid cyst without any episode of injury. The patient complained of neck swelling after exercise and went to a nearby hospital. At the hospital, the doctor thought this swelling was caused by retropharyngeal bleeding from a tumor behind the left thyroid gland. Embolization of the left thyroid artery was performed. However, the next day, airway obstruction.was occurred and she was brought to our hospital. An emergency operation was performed to open the left neck swelling region. The operation findings and pathological examination showed that the bleeding was caused by a parathyroid cyst and airway obstruction had occurred because of retropharyngeal edema. In this case, the bleeding may have been caused by torsion of the neck when the patient exercised. The retropharyngeal edema probably resulted from the delay of delivery of the lymphatic and venous return and the arterial embolization. 1 year after the operation, the patient is very well and there has been no recurrence.

The inner ear is constituted by complicated cochlear and vestibular compartments, which are derived from the otic vesicle, an embryonic structure of ectodermal origin. Although the inner ear development has been analyzed using various techniques, the developmental events have not been fully elucidated because of the intricate structure. We previously developed a Sox10-IRES-Venus mouse designed to express green fluorescent protein under the control of the Sox10 promoter. In the present study, we showed that the Sox10-IRES-Venus mouse enabled the non-destructive visualization and understanding of the morphogenesis during the development of the inner ear. The expression of the transcription factor Sox10 was first observed in the invaginating otic placodal epithelium, and continued to be expressed in the mature inner ear epithelium except for the hair cells and mesenchymal cells. We found that Sox10 was expressed in immature hair cells in the developing inner ear, suggesting that hair cells were generated from the Sox10-expressing prosensory cells. Furthermore, we demonstrated that scattered Sox10-expressing cells existed around the developing inner ear, some of which differentiated into pigmented melanocytes in the stria vascularis, suggesting that they were neural crest cells. Further analyzing the Sox10-IRES-Venus mice would provide important information to better understand the development of the inner ear.

The activation of oncogenic signaling pathways induces the reprogramming of glucose metabolism in tumor cells and increases lactic acid secretion into the tumor microenvironment. This is a well-known characteristic of tumor cells, termed the Warburg effect, and is a candidate target for antitumor therapy. Previous reports show that lactic acid secreted by tumor cells is a proinflammatory mediator that activates the IL-23/IL-17 pathway, thereby inducing inflammation, angiogenesis and tissue remodeling. Here, we show that lactic acid, or more specifically the acidification it causes, increases arginase I (ARG1) expression in macrophages to inhibit T-cell proliferation and activation. Accordingly, we hypothesized that counteraction of the immune effects by lactic acid might suppress tumor development. We show that dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinases, targets macrophages to suppress activation of the IL-23/IL-17 pathway and the expression of ARG1 by lactic acid. Furthermore, lactic acid-pretreated macrophages inhibited CD8+ T-cell proliferation, but CD8+ T-cell proliferation was restored when macrophages were pretreated with lactic acid and DCA. DCA treatment decreased ARG1 expression in tumor-infiltrating immune cells and increased the number of IFN-γ-producing CD8+ T cells and NK cells in tumor-bearing mouse spleen. Although DCA treatment alone did not suppress tumor growth, it increased antitumor immunotherapeutic activity of Poly(IC) in both CD8+ T cell- and NK cell-sensitive tumor models. Therefore, DCA acts not only on tumor cells to suppress glycolysis but also on immune cells to improve the immune status modulated by lactic acid and to increase the effectiveness of antitumor immunotherapy.

Maternally inherited diabetes and deafness (MIDD) is a rare subtype form of diabetes caused by a mitochondrial DNA defect associated with m.3243A>G mutation. More than 90% of MIDD cases suffer from bilateral progressive sensorineural hearing loss. Here, we report two cases of MIDD with bilateral profound hearing loss that were successfully treated with cochlear implantation. Case 1 was a 61-year-old man who complained of bilateral progressive hearing loss since the age of 40 years old and who visited our department seeking treatment. He was diagnosed as having MIDD based on a genetic analysis of mitochondrial DNA that revealed a 3243 A to G substitution. Cochlear implantation (CI) was performed for the right ear, which exhibited profound hearing loss. At 5 years after the CI, the patient had acquired hearing function enabling more than 90% of spoken words to be discriminated. Case 2 was a 44-year-old woman who had suffered from diabetes and deafness since the age of 24 years and who had a 3243 A to G substitution in her mitochondrial DNA. She visited our department for cochlear implantation because hearing aids had never improved her hearing. At 6 years after the CI, she had acquired good speech discrimination. We suggest that CI might be a useful treatment for profound hearing loss in patients with MIDD.

Objectives Tinnitus interferes with sleep and concentration which is associated with depression; however, no drug has been effective in treating tinnitus. Our purpose is to evaluate our hypothesis that the treatment with lyophilized powder of enzymolyzed honeybee larvae as a complementary medicine may provide a therapeutic effect on tinnitus-related symptoms. Design Sixty tinnitus sufferers participated in a randomized double-blind placebo-controlled trial using the lyophilized powder of enzymolyzed honeybee larvae or a placebo. The Tinnitus Handicap Inventory, a visual analog scale to rate the severity of tinnitus, hearing levels, and hypothalamus-pituitary-adrenal axis-related hormones drawn early in the morning were measured upon entry into the study and after 12 wk of follow-up. Results The lyophilized powder of enzymolyzed honeybee larvae was not superior to placebo with regard to the total score on the Tinnitus Handicap Inventory and the visual analog scale. However, subjects in the honeybee larvae group showed significant improvements in some items about depression associated with tinnitus, whereas subjects in the placebo group showed no improvement in any items. The honeybee larvae group showed significant improvements in the hearing levels at 2 and 4 kHz in the audiogram of the better ear. The intervention of the lyophilized powder of enzymolyzed honeybee larvae was associated with lower serum cortisol levels, serum prolactin levels, and cortisol/dehydroepiandrosterone sulfate ratios. The ratios in the placebo group significantly were increased. Conclusions Our results suggest that the lyophilized powder of enzymolyzed honeybee larvae represents an effective complementary medicine to alleviate depression associated with tinnitus by regulating the activity of the hypothalamus-pituitary-adrenal axis.