Effectiveness of a programable body-worn digital hearing aid for older adults in a developing country: a randomized controlled trial with a cross-over design.

BACKGROUND: Hearing aids are important assistive devices for hearing rehabilitation. However, the cost of commonly available commercial hearing aids is often higher than the average monthly income of individuals in some developing countries. Therefore, there is a great need to locally produce cheaper, but still effective, hearing aids. The Thai-produced P02 hearing aid was designed to meet this requirement. OBJECTIVE: To compare the effectiveness of the P02 hearing aid with two common commercially available digital hearing aids (Clip-II™ and Concerto Basic®). METHODS: A prospective, randomized controlled trial with a cross-over design was conducted from October 2012 to September 2014 in a rural Thai community. There were 73 participants (mean age of 73.7 ± 7.3 years) included in this study with moderate to severe hearing loss who were assessed for hearing aid performance, including probe microphone real-ear measurement, functional gain, speech discrimination, and participant satisfaction with the overall quality of perceived sound and the design of the device. RESULTS: There were no statistically significant differences in functional gain or speech discrimination among the three hearing aids evaluated (p-value > 0.05). Real-ear measurements of the three hearing aids met the target curve in 93% of the participants. The best real-ear measurement of the hearing aid following the target curve was significantly lower than that of Clip-II™ and Concerto Basic® (p-value < 0.05) at high frequency. However, participants rated the overall quality of sound higher for the P02 hearing aid than that of Clip-II™ but lower than that of Concerto Basic® (p-value > 0.05). Participants revealed that the P02 hearing aid provided the highest satisfaction ratings for design and user-friendliness with statistical significance (p-value < 0.05). CONCLUSION: The P02 hearing aid was an effective device for older Thai adults with hearing disabilities. Additionally, its modern design, simplicity of use, and ease of maintenance were attractive to this group of individuals. These benefits support the rehabilitation potential of this hearing aid model and its positive impact on the quality of life of older adults in developing countries. TRIAL REGISTRATION: This study was registered under Clinicaltrial.gov NCT01902914 . Date of registration: July 18, 2013.

Sinus and anterior skull base surgery during the COVID-19 pandemic: systematic review, synthesis and YO-IFOS position.

PURPOSE: The COVID-19 pandemic has caused significant confusion about healthcare providers' and patients' pandemic-specific risks related to surgery. The aim of this systematic review is to summarize recommendations for sinus and anterior skull base surgery during the COVID-19 pandemic. METHODS: PubMed/MEDLINE, Google Scholar, Scopus and Embase were searched by two independent otolaryngologists from the Young Otolaryngologists of IFOS (YO-IFOS) for studies dealing with sinus and skull base surgery during COVID-19 pandemic. The review also included unpublished guidelines edited by Otolaryngology-Head and Neck Surgery or Neurosurgery societies. Perioperative factors were investigated including surgical indications, preoperative testing of patients, practical management in operating rooms, technical aspects of surgery and postoperative management. The literature review was performed according to PRISMA guidelines. The criteria for considering studies or guidelines for the review were based on the population, intervention, comparison, outcome, timing and setting (PICOTS) framework. RESULTS: 15 International publications met inclusion criteria. Five references were guidelines from national societies. All guidelines recommended postponing elective surgeries. An algorithm is proposed that classifies endonasal surgical procedures into three groups based on the risk of postponing surgery. Patients' COVID-19 status should be preoperatively assessed. Highest level of personal protective equipment (PPE) is recommended, and the use of high-speed powered devices should be avoided. Face-to-face postoperative visits must be limited. CONCLUSIONS: Sinus and skull base surgeries are high-risk procedures due to potential aerosolization of SARS-CoV-2 virus. Protection of health care workers by decreasing exposure and optimizing the use of PPE is essential with sinus and anterior skull base surgery.

Is Adjunctive Hyperbaric Oxygen Treatment Alone or with Surgery the Proper Management for Active and Persistent Osteoradionecrosis?

ABSTRACT: This study enrolled patients with stage 3 osteoradionecrosis. There were three treatment modalities: antibiotics, hyperbaric oxygen therapy (HBOT), and surgery. Complete healing was the primary outcome. Multiple logistic regression analysis demonstrated that surgery with HBOT improved wound healing better than HBOT alone.

Increasing incidence of Epstein-Barr virus-related nasopharyngeal carcinoma in the United States.

BACKGROUND: The incidence of nasopharyngeal carcinoma (NPC) has been historically low in the United States. Although etiological factors differ by histological subtype, Epstein-Barr virus is accepted as the primary risk factor for nonkeratinizing NPC. In light of the changing epidemiology of viral-associated cancers, it is important to evaluate the temporal incidence of NPC in the United States. METHODS: Incidence and survival data from 1973 through 2015 were obtained from the Surveillance, Epidemiology, and End Results program. Stratified analyses were conducted to assess temporal trends in NPC by histological subtype, sex, and race. The data were analyzed using SAS and Joinpoint Regression Software to determine age-adjusted incidence rates, determine trends in the annual percent change, and calculate 5-year relative survival estimates and Kaplan-Meier curves. RESULTS: Although overall NPC incidence is decreasing in the United States, the nonkeratinizing differentiated subtype is starkly increasing, with an annual percent change of approximately 4% among white males (95% CI, 2.5%-5.2%), white females (95% CI, 1.9%-6.2%), and black males (95% CI, 2.0%, 5.7%); 2.7% among black females (95% CI, 0.8%, 4.6%); and 1.8% among women in the "other" race category (95% CI, 0.4%-3.3%). Racial disparities were noted, with 32% of nonkeratinizing NPC cases among blacks occurring before the age of 40 years. In addition, black males displayed consistently worse survival across all histological subtypes, whereas individuals in the "other" race category, particularly females, experienced the highest 5-year relative survival estimates. CONCLUSIONS: The current results indicate that the Epstein-Barr virus-related, differentiated NPC subtype is increasing across all sexes and races in the United States, with distinct incidence and survival disparities among blacks.

Human papillomavirus (HPV) infection in a case-control study of oral squamous cell carcinoma and its increasing trend in northeastern Thailand.

Human papillomavirus (HPV) is an independent risk factor for development of oral squamous cell carcinoma (OSCC). This study aimed to investigate the role of HPV infection and the trend in percentage of HPV-associated OSCC over a 5-year period in northeastern Thailand. In this case-control study, 91 exfoliated oral cell samples and 80 lesion cell samples from OSCC cases and exfoliated oral cells from 100 age/gender-matched controls were collected. HPV infection was investigated by PCR using GP5+/GP6+ primers followed by HPV genotyping using reverse line blot hybridization. Quantitative RT-PCR was used to evaluate HPV oncogene transcription. Temporal trends of HPV infection were evaluated in archived formalin-fixed paraffin-embedded (FFPE) OSCC tissues using in situ hybridization. HPV DNA was found in 17.5% (14/80) of lesion samples from OSCC cases and 29.7% (27/91) of exfoliated oral cell samples from the same cases. These values were significantly higher than in exfoliated oral cell samples from controls (13%, 13/100). HPV-16 was the genotype most frequently found in OSCC cases (92.8%, 13/14 infected cases). Interestingly, HPV oncogene mRNA expression was detected and correlated with OSCC cases (P < 0.005). Of 146 archived FFPE OSCC samples, 82 (56.2%) were positive for high-risk HPV DNA and 64 (43.8%) cases were positive for HPV E6/E7 mRNA expression. There was a trend of increasing percentage of HPV-associated OSCC from 2005 to 2010. This was especially so for females with well-differentiated tumors in specific tongue sub-sites. We suggest that HPV infection plays an important role in oral carcinogenesis in northeastern Thailand.

Ear, Nose, Throat and Craniofacial Diseases Community Services Initiative of Khon Kaen University.

The Department of Otorhinolaryngology, Faculty of Medicine, Khon Kaen University has cooperated with the local community to establish the welfare and health education service in the local community. The first initiative was carried out in the local primary school. This paper described the missions, method and results of our first attempt to screen the students in the community.

Association of Epstein-Barr virus infection with oral squamous cell carcinoma in a case-control study.

BACKGROUND: Besides the well-known risk factors, Epstein-Barr virus (EBV) might play a significant role in oral squamous cell carcinoma (OSCC). To explore the role of EBV in OSCC, the prevalence of EBV infection in oral exfoliated cells of OSCC cases and controls in northeastern Thailand was investigated, and the association of EBV in tumor lesion cells was further confirmed. METHODS: Oral exfoliated cells were collected from OSCC cases and non-cancer controls. Cells from tumor lesions were taken from OSCC patients for further strong confirmation of the association of EBV with OSCC. EBV DNA was detected by polymerase chain reaction (PCR) using primers specific for EBV DNA polymerase. The EBV DNA positive samples were confirmed further by nested PCR. RESULTS: Epstein-Barr virus was detected in the oral exfoliated cells of 45.05% of OSCC patients and 18.08% of the non-cancer control (P < 0.001). Similarly, EBV was detected in 32.5% of the tumor lesions. Betel quid chewing was statistically significantly associated with EBV prevalence (OR = 2.08), whereas no association with tobacco smoking and alcohol consumption. Alcohol consumption and betel quid chewing were significantly associated with OSCC (OR = 3.05 and OR = 5.05, respectively), but tobacco smoking was not associated. Interestingly, EBV was significantly associated with OSCC (OR = 3.76). CONCLUSIONS: Epstein-Barr virus prevalence is associated with OSCC and seems to be enhanced by betel quid chewing, suggesting that EBV may, together with betel quid chewing, act as an important etiological risk factor of OSCC.

Once or twice daily versus three times daily amoxicillin with or without clavulanate for the treatment of acute otitis media.

BACKGROUND: Acute otitis media (AOM) is a common problem in children, for which amoxicillin, with or without clavulanate, is frequently prescribed as a treatment of choice. The conventional recommendation is either three or four daily doses. However, nowadays it is frequently prescribed as once or twice daily doses. If once or twice daily amoxicillin, with or without clavulanate, is as effective for acute otitis media as three or four times a day, it may be more convenient to give the medication once or twice a day to children and hence improve compliance. OBJECTIVES: To compare the effectiveness of one or two daily doses with three or four daily doses of amoxicillin, with or without clavulanate, for the treatment of AOM in children; and to compare complication rates and adverse reactions. SEARCH METHODS: We searched CENTRAL 2013, Issue 2, MEDLINE (January 1950 to March week 1, 2013), EMBASE (1974 to March 2013) and the Science Citation Index (2001 to March 2013). SELECTION CRITERIA: We included randomised controlled trials (RCTs) of children aged 12 years or younger with AOM, diagnosed by acute ear pain (otalgia) and inflamed ear drum (confirmed by positive tympanocentesis or tympanogram of type B or C). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data on treatment outcomes from individual trials and assessed trial quality based on selection bias, performance bias and detection bias, attrition bias, reporting bias and other biases. We defined the quality grading as low risk of bias, high risk of bias or unclear risk of bias. We summarised the results as risk ratio (RR) with 95% confidence intervals (CI). MAIN RESULTS: We included five studies with 1601 children in the review. Pooled analysis demonstrated that the following outcomes were comparable between the two groups: clinical cure at the end of therapy (RR 1.03, 95% CI 0.99 to 1.07); during therapy (RR 1.06, 95% CI 0.85 to 1.33) and at follow-up (RR 1.02, 95% CI 0.95 to 1.09); recurrent AOM (RR 1.21, 95% CI 0.52 to 2.81); compliance rate (RR 1.04, 95% CI 0.98 to 1.10) and overall adverse events (RR 0.92, 95% CI 0.52 to 1.63). When we performed subgroup analysis separately for trials with amoxicillin only and amoxicillin/clavulanate only, it showed that all important outcomes were comparable between once or twice daily groups and the three times daily group. The risk of bias amongst the five included studies was as follows: for random sequence generation we graded two studies as low and three unclear risk of bias; for allocation concealment all studies were at unclear risk of bias; for blinding (performance and detection bias) we graded four as high and one as unclear risk of bias; for incomplete outcome data (attrition bias) we graded two low, two high and one as unclear risk of bias; for reporting bias four were at low and one at high risk; and for 'other' bias four were at low and one at unclear risk of bias. AUTHORS' CONCLUSIONS: This review showed that the results of using once or twice daily doses of amoxicillin, with or without clavulanate, were comparable with three doses for the treatment of AOM.

An in vitro model and the underlying pathways of sinonasal inverted papilloma development.

Recently, the specific association between Sinonasal inverted papilloma (SIP) and EGFR exon 20 mutations has been reported. To investigate the link between specific EGFR mutations and SIP development, we established organotypic raft culture system using nasal polyp-derived immortalized NP2 (iNP2) cells expressing EGFR exon 20 mutants or an exon 19 mutant, and SIP-derived iIP4 cells harboring P772_H773insPYNP mutation. In the raft culture, iIP4 cells showed the inverted growth pattern characteristic to SIP. Interestingly, iNP2 cells expressing EGFR exon 20 duplication mutants, S768_D770dup and N771_H773dup, but not of EGFR exon 19 mutant, E746_A750del, showed the inverted growth pattern. Enhanced activation of the PI3K/AKT signaling pathway was observed in iNP2_S768_D770dup and iIP4 cells, while increased MAPK signaling was found in iNP2_N771_H773dup. Increased cell migration and invasion were found in all cells carrying EGFR mutations when compared to iNP2 cells, and this effect was inhibited by either PI3K or MEK inhibitor. Notably, iNP2 cells expressing the N771_H773dup mutant showed the highest migration and invasion abilities. These results suggest that specific mutations in EGFR exon 20 play a crucial role in SIP development, partially though hyper-activation of the PI3K/AKT and MAPK signaling pathways. This study presents the first in vitro model for SIP development, which could facilitate further investigations into SIP pathogenesis and preclinical studies for new therapeutic agents.

Frontal sinus drainage in Thai adult skulls.

OBJECTIVE: To study the pattern of the nasofrontal drainage in relation to the neighboring anatomical structures in adult Thai cadavers. MATERIAL AND METHOD: The anterior aspect of the frontal bone of the embalmed half-head was drilled to identify the presence of the frontal sinus i.e. 40 from only one side of each cadaver were chosen. A silicone base and catalyst were combined then injected into the frontal sinus, which flowed into the nasal cavity through its natural ostium, thereby creating a cast of the nasofrontal connection(s). After allowing five minutes for the silicone to set, the total vertical lamella of the middle turbinate was removed, so the cast could be measured, the connections meticulously dissected and the surrounding structures observed RESULTS: The investigation revealed five patterns of nasofrontal drainage. The most (60%) common pathway was directly through the frontal recess, while the other pathways 12.5, 10, 10 and 7.5 percent were drained directly into the ethmoid infundibulum, through the agger nasi cell and then into the ethmoid infundibulum, into both the agger nasi cell, the ethmoid infundibulum and the suprabullar recess, respectively. The average sizes of the anteroposterior and mediolateral diameters of the frontal sinus ostium were 6.5 and 5.5 mm, respectively. The agger nasi cell was present in every cadaver with a frontal sinus and was always superior to the ventral attachment of the middle turbinate. CONCLUSION: The agger nasi cell is the key structure vis-a-vis planning and performing frontal sinus surgery. In preparation for endoscopic intranasal frontal sinus surgery, it is practical to extend the infundibulotomy superiorly into the agger nasi cell, then remove its medial, posterior and superior wall.

Landmark of ethmoid arteries in adult Thai cadavers: application for sinus surgery.

BACKGROUND: Ethmoid arteries, branches of the ophthalmic artery, are crucial structures supplying ethmoid mucosa. Its locations are important during ethmoid sinus surgery. There has been no study in Thais before. OBJECTIVE: To determine the number and locations of ethmoid arteries in relation to important surrounding structures. MATERIAL AND METHOD: A prospective, descriptive study in 42 Thai cadaveric adult half-heads was conducted at departments of Otorhinolaryngology and Anatomy, Faculty of Medicine, Khon Kaen University, Thailand. Meticulous dissections were performed to identify number of ethmoid arteries branching from ophthalmic artery and site of entrance of the arteries into ethmoid sinus. Relationships of these arteries with anterior ethmoid crest, optic foramen, bulla lamella and middle third of basal lamella of middle turbinate were studied. OUTCOMES: Types of ethmoid arteries, distances between ethmoid arteries and their relations to important surrounding structures: anterior lacrimal crest, optic foramen, superior aspects of bulla lamella, middle third of basal lamella of middle turbinate and the superior aspect of anterior wall of sphenoid sinus. RESULTS: All specimens had anterior and posterior ethmoid arteries. The prevalence of tertiary ethmoid artery was 36% (95% CI22-52%). The mean distance between the anterior ethmoid artery and anterior lacrimal crest, anterior ethmoid artery and posterior ethmoid artery and the distance between posterior ethmoid artery and optic foramen were 24.3, 13.5 and 6.4 millimeters respectively. Most of the entry of anterior ethmoid artery into the ethmoid sinus was in the posterior half of the distance between the bulla lamella and middle third of basal lamella of middle turbinate, 85.7%. CONCLUSION: This is the first study of location of ethmoid arteries in Thai adult cadavers. The information of the present study may be useful for sinus surgeon.

The burden of head and neck cancers in Thailand.

OBJECTIVE: To determine the overall burden of disease vis-a-vis head and neck cancers in Thailand, as indicated by visits to healthcare units, admissions for treatment and expenditures at all levels of the healthcare delivery system. MATERIAL AND METHOD: A descriptive study was conducted by retrieving and analysing data for the fiscal year 2010 from the National Health Security Office (NHSO) and the Social Security Office, Thailand and from in-patient data of the Civil Servants Benefit System from the Comptroller General's Department. RESULTS: In 2010, there were 167,199 visits to outpatient departments (OPDs) and 26,012 admissions to hospital (IPD) for diagnosis and treatment of head and neck cancers. The most common diagnosis for visits to OPD and admission to IPD was oral cancer (28.2% and 25%, respectively). The mean length of hospital stay was 9 days. About half of admissions took place in the central region. The hospital charges totalled 691 million Baht (US$ 21.8 million), or an average of 26,556 Baht (USS 838) per admission. CONCLUSION: Since a relatively high volume of hospital visits was found, there is an urgent need to train sufficient numbers of specialists in the field of head and neck cancer treatments to provide efficient healthcare.

Association of Human Papillomavirus and Epstein-Barr Virus Infection with Tonsil Cancer in Northeastern Thailand.

BACKGROUND: Human papillomavirus (HPV) and Epstein-Barr virus (EBV) are associated with head and neck cancer, including tonsil cancer (TC) in the oropharyngeal area. Increasing incidence of HPV and EBV infection in different cancer tissues of oropharynx in both epithelial and lymphoid tissues, have been reported. However, little is known about association of these tumor viruses with TC in the Thai population. Here, we investigated the prevalence of HPV and EBV infection in different histology of TC and their association with TC from Thai patients. METHODS: Eighty-three exfoliated tonsil cells from non-cancer controls (NCC) and 65 formalin-fixed paraffin-embedded TC tissues (TC) that were histologically classified as tonsillar squamous-cell carcinoma (TSCC) or diffuse large B-cell lymphoma (DLBCL) were studied. Prevalence of HPV and EBV infection was determined by real-time PCR. HPV genotyping was performed by reverse line blot hybridization and HPV genome status was investigated by multiplex qPCR. Localization of EBV infection was determined by EBER in situ hybridization. RESULTS: Infection of HPV and EBV in TC cases was 16.9% and 30.8%, whereas in exfoliated tonsil cells was 1.2% and 66.3% respectively. HPV infection was significantly higher in TSCC (30.6%) than DLBCL samples (13.8%). HPV58 was commonly detected and presented as an integrated form in TSCC, whereas only episomal form was found in DLBCL. EBV infection was significantly higher in DLBCL (44.8%) than TSCC samples (19.4%), and detected in both lower than among exfoliated tonsil cell samples (66.3%). By EBER in situ hybridization in TSCC, EBV infection localized both in epithelial cells and infiltrating lymphocytes. The co-occurrence of HPV and EBV infection was 11.11% and 13.79% of TSCC and DLBCL, respectively, was associated with well-differentiated TSCC. CONCLUSION: HPV and EBV infection was significantly involved in a specific TC tissue, and associated with a good clinical outcome in TSCC.

Human Papillomavirus 16 E6 Suppresses Transporter Associated with Antigen-Processing Complex in Human Tongue Keratinocyte Cells by Activating Lymphotoxin Pathway.

Infection by high-risk human papillomaviruses (hrHPVs), including HPV type 16 (HPV16), is a major risk factor for oral squamous cell carcinomas (OSCCs). However, the pathogenic mechanism by which hrHPVs promote oral carcinogenesis remains to be elucidated. Here, we demonstrated that the suppression of a transporter associated with the antigen-processing complex (TAPs; TAP1 and TAP2), which is a key molecule in the transportation of viral antigenic peptides into MHC class-I cells, is affected by the E6 protein of HPV16. Mechanistically, HPV-mediated immune evasion is principally mediated via the signal-transduction network of a lymphotoxin (LT) pathway, in particular LTα1ß2 and LTßR. Our analysis of transcriptomic data from an HNSCC cohort from the Cancer Genome Atlas (TCGA) indicated that expression of TAP genes, particularly TAP2, was downregulated in HPV-infected cases. We further demonstrated that LTα1ß2 and LTßR were upregulated, which was negatively correlated with TAP1 and TAP2 expression in HPV-positive clinical OSCC samples. Taken together, our findings imply that HPV16 E6 regulates the machinery of the antigenic peptide-loading system and helps to clarify the role of oncogenic viruses in the context of oral carcinoma.

Barriers to early detection and management of oral cancer in the Asia Pacific region.

OBJECTIVE: Oral cancer is amenable to early detection but remains a prominent cause of mortality in the Asia Pacific region. This study aimed to identify barriers to early detection and management of oral cancer in the Asia Pacific region. METHODS: A mixed-methods approach was employed triangulating findings from a survey and focus groups. The survey was conducted among seven representative members of the Asia Pacific Oral Cancer Network (APOCNET) across six countries. Focus groups were conducted to gain deeper insights into the findings of the survey. RESULTS: The identified barriers were a lack of national cancer control strategies and cancer registries and the limited availability of trained health care professionals. Overcoming these challenges in the Asia Pacific region where resources are scarce will require collaborative partnerships in data collection and novel approaches for continuous professional training including eLearning. Further, to overcome the lack of trained health care professionals, innovative approaches to the management of oral potentially malignant lesions and oral cancer including telemedicine were suggested. CONCLUSION: The findings of this study should be taken into account when charting national cancer control plans for oral cancer and will form the basis for future collaborative studies in evaluating effective measures to improve oral cancer detection and management in low- and middle-income countries.

Survival of Cancer Patients with Co-Morbid Tuberculosis in Thailand.

BACKGROUND AND OBJECTIVE: We aimed to investigate the survival time and its related factors among cancer patients with co-morbid tuberculosis (TB) in Thailand. METHODS: We conducted this retro-prospective cohort study on cancer patients without co-morbid TB using the data from population-based cancer registry of Khon Kaen, TB databases from the Khon Kaen Central Hospital, and the Region 7 Office of Disease Prevention and Control from 2001 to 2015 to determine the onset of TB after cancer. The cancer patients were then followed up until 2017 to assess their survival status. The Kaplan-Meier method, log-rank test, and Cox proportional hazard regression were used to estimate cumulative survival curves, compare various survival distributions, and adjusted hazard ratios. RESULTS: Lung, head and neck, and liver cancers led to a  significantly different survival time between patients with and without co-morbid TB. After adjustment, it was found that patients suffering from lung, head and neck, or liver cancer and co-morbid TB had significantly lower risk of death than those without co-morbid TB. Based on the stratified analysis, lung cancer patients with distant metastasis and co-morbid TB had 3.01-fold and 2.99-fold significantly increased risk of death compared to those without co-morbid TB. CONCLUSION: We found that cancer patients with co-morbid TB were at lower risk of death compared with those without co-morbid TB. In addition to cancer stage, it seems that cancer comorbidity with TB could modify the risk of death for lung cancer patients.There is a need for further studies to support our findings including other related risk factors. 
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Epstein-Barr Virus-Associated Langerhans Cell Histiocytosis of the Thyroid Gland.

Thyroid gland involvement of Langerhans cell histiocytosis (LCH) is extremely rare in both systemic and isolated disease. The role of viral infection in LCH development is not yet fully understood. Although several viruses are proposed as etiologic factors, such as Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6), they seem to play a bystander role in LCH. A 29-year old female patient with a prior history of multisystemic LCH (pituitary gland and skull bone), presented with a thyroid nodule. The patient underwent a total thyroidectomy and the histological examination revealed nodular lesions composed of sheets and clusters of histiocytes in the inflammatory background. The histiocytes stained positive for S-100 and CD1a and were negative for HHV-8, cytomegalovirus, and VE1 (anti-BRAFV600E) on immunohistochemistry. The EBER in situ hybridization for EBV showed frequent positive-stained cells. The conventional PCR analysis for EBV was positive and qPCR analysis confirmed a significant DNA copy number difference (p = 0.02) between the tumor and adjacent non-neoplastic thyroid tissue. PCR analysis for HHV-6, HPV, HSV was negative in both tumor and benign samples. In conclusion, the presented case showed a rare thyroid involvement by LCH associated with EBV infection, which has not been reported before. Further studies are required to investigate a possible etiologic link between EBV infection and LCH.

Exosomes-carrying Epstein-Barr virus-encoded small RNA-1 induces indoleamine 2, 3-dioxygenase expression in tumor-infiltrating macrophages of oral squamous-cell carcinomas and suppresses T-cell activity by activating RIG-I/IL-6/TNF-α pathway.

OBJECTIVES: Although exosomes carrying Epstein-Barr virus-encoded small RNA-1 (EBER-1) are involved in the immunosuppressive tumor microenvironments of EBV-associated head and neck carcinomas, the effects of EBER-1-associated exosomes on tumor-infiltrating macrophages are poorly understood. MATERIALS AND METHODS: The association between EBV infection and expression of indoleamine 2,3-dioxygenase (IDO) was assessed in 165 paraffin-embedded oral squamous cell carcinoma (OSCC) tissue samples. Using in vitro techniques, we investigated whether stimulation of the RIG-I/IL-6/TNF-α pathway by exosomes carrying EBER-1 is critical for IDO induction in macrophages. We performed a thymidine incorporation and a cell cytolytic assay to test for up-regulated IDO in macrophages that can block the proliferation and function of effector T cells. RESULTS: Some infiltrated macrophages expressed levels of IDO higher than OSCC cells which was significantly associated with presence of EBV. The production of IDO, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in human monocyte-derived macrophages (MDMs) was induced by EBV-associated exosomes in vitro. Mechanistically, the retinoic acid-inducible gene I (RIG-I) pathway in MDMs was stimulated by EBV-encoded small RNA-1 (EBER-1) whereas the inhibition of these pathways by BX-795 almost abolished the production of these two cytokines and IDO induction. Also, the EBER-1-activated IDO in MDMs suppressed the proliferation of T lymphocytes and diminished the cytolytic activity of CD8+ T cells. CONCLUSION: Exosomes carrying EBER-1 could induce IDO expression in MDMs, considerably aided by an IL-6 and TNF-α-dependent mechanism via the RIG-I signaling pathway, which might create an immunosuppressive microenvironment affecting T-cell immune responses.