Clinical performance, safety, and patient-reported outcomes of an active osseointegrated bone-conduction hearing implant system at 24-month follow-up.

PURPOSE: To investigate 2-year post-operative hearing performance, safety, and patient-reported outcomes of hearing-impaired adults treated with the Osia® 2 System, an active osseointegrated bone-conduction hearing implant that uses piezoelectric technology. METHODS: A prospective, multicenter, open-label, single-arm, within-subject clinical study conducted at three tertiary referral clinical centers located in Melbourne, Sydney and Hong Kong. Twenty adult recipients of the Osia 2 System were enrolled and followed up between 12 and 24 months post-implantation: 17 with mixed or conductive hearing loss and 3 with single-sided sensorineural deafness. Safety data, audiological thresholds, speech recognition thresholds in noise, and patient-reported outcomes were collected and evaluated. In addition, pre-and 6-month post-implantation data were collected retrospectively for this recipient cohort enrolled into the earlier study (ClinicalTrials.gov NCT04041700). RESULTS: Between 6- and 24-month follow-up, there was no statistically significant change in free-field hearing thresholds or speech reception thresholds in noise (p = > 0.05), indicating that aided improvements were maintained up to 24 months of follow-up. Furthermore, improvements in health-related quality of life and daily hearing ability, as well as clinical and subjective measures of hearing benefit remained stable over the 24-month period. No serious adverse events were reported during extended follow-up. CONCLUSIONS: These study results provide further evidence to support the longer term clinical safety, hearing performance, and patient-related benefits of the Osia 2 System in patients with either a conductive hearing loss, mixed hearing loss, or single-sided sensorineural deafness. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04754477. First posted: February 15, 2021.

Applying computer-based language test to young children.

INTRODUCTION: This study aims at exploring the feasibility of applying a computer-based language test to young children aged 2-4 years. METHODS: Thirty-two Cantonese-speaking children, aged 2-4 years, were recruited from local kindergartens. All participants underwent assessment using both the computer-based and paper-pencil versions of the Macau Cantonese Language Screening Scale for Preschool Children, following a crossover study design. A short break of 15-30 minutes was provided between the two assessments. The data were analysed at three levels: the overall test, subcategory, and individual item levels. At the overall test and subcategory levels, data were analysed using the paired samples t-test and ICC. At the item level, the percentage of agreement and Cohen's kappa value were selected to assess the agreement of the two test formats. RESULTS: Excellent agreement was found for the overall test level, and good agreement was observed for four of the five subcategories. At the individual item level, 28 of the 35 items showed more than 80% agreement, and 16 items showed substantial to almost perfect agreement. CONCLUSION: These results suggest that the two test formats give similar total scores and subcategory scores for children aged 2-4. For children older than 2 years, 6 months, the agreement for matching items is as high as 83.68% (1318/1575). The computer-based test is thus highly recommended for this group of children. For children younger than 2 years, 6 months, a modified computer-based test is suggested to accommodate their needs.

The R292K mutation that confers resistance to neuraminidase inhibitors leads to competitive fitness loss of A/Shanghai/1/2013 (H7N9) influenza virus in ferrets.

BACKGROUND: Neuraminidase (NA) inhibitors are the only licensed therapeutic option for human zoonotic H7N9 infections. An NA-R292K mutation that confers broad-spectrum resistance to NA inhibitors has been documented in H7N9 patients after treatment. METHODS: We evaluated the transmission potential of a human influenza A H7N9 isolate with a NA-R292K mutation in the ferret model followed by genotyping assay to monitor its competitive fitness in vivo. RESULTS: Plaque-purified A/Shanghai/1/2013 wild-type and NA-R292K viruses transmitted at comparable efficiency to direct or respiratory droplet contact ferrets. In ferrets inoculated with the plaque-purified A/Shanghai/1/2013 NA-R292K virus with dominant K292 (94%), the resistant K292 genotype was outgrown by the wild-type R292 genotype during the course of infection. Transmission of the resistant K292 genotype was detected in 3/4 direct contact and 3/4 respiratory droplet contact ferrets at early time points but was gradually replaced by the wild-type genotype. In the respiratory tissues of inoculated or infected ferrets, the wild-type R292 genotype dominated in the nasal turbinate, whereas the resistant K292 genotype was more frequently detected in the lungs. CONCLUSIONS: The NA inhibitor-resistant H7N9 virus with the NA-R292K mutation may transmit among ferrets but showed compromised fitness in vivo while in competition with the wild-type virus.

Early detection of phlebitis among hematology-oncology patients: a best practice implementation project.

INTRODUCTION: Peripherally-inserted venous catheters (PIVC) are essential for cancer patients to receive treatment. Phlebitis is a major complication of PIVC. Currently, nurses' assessment of phlebitis mainly involves visual inspection. However, the latest literature suggests palpation for tenderness to promote the early detection of phlebitis. OBJECTIVES: This project evaluated the effectiveness of a bundle approach to increase nurses' compliance with PIVC site assessment to promote early detection of phlebitis (grade 2 and above). METHODS: The JBI Evidence Implementation Framework was used to conduct this project in a 28-bed hematology-oncology ward in a Singapore hospital. The bundle approach used in this project consisted of a training presentation, medical mannequin, and phlebitis scale card. The rate of nurses' compliance with best practice for PIVC site assessment was measured at 1 month and 6 months post-implementation. The incidence of phlebitis was monitored up until 12 months post-implementation. RESULTS: Baseline data indicated that only 18.75% (3 out of 16) nurses palpated for tenderness when assessing for phlebitis. Data at 1 month and 6 months post-implementation reported sustained high compliance rates of 85.71% (24 out of 28) and 89.29% (25 out of 28), respectively. Late detection of phlebitis was reduced by 66% (from three cases to one case) at 6 months post-implementation, and no patients required invasive interventions. CONCLUSIONS: The bundle approach used in this project facilitated early detection of phlebitis following the inclusion of palpation into nurses' assessment for phlebitis. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A204.

Phenotypic and functional characterization of human γδ T-cell subsets in response to influenza A viruses.

Like αß T cells, human γδ T cells also have different subsets with distinct characteristics. Whether human Vγ9Vδ2 T cells have functionally different subsets in response to influenza A (fluA) viruses remains unknown. In this study, we show for the first time that both central (CD45RA(-)CD27(+)) and effector (CD45RA(-)CD27(-)) memory Vγ9Vδ2 T cells have similar levels of immediate interferon (IFN) γ and cytotoxic responses to human and avian fluA virus-infected cells. In contrast, CD56(+) Vγ9Vδ2 T cells have significantly higher cytotoxicity against fluA virus-infected cells compared with their CD56(-) counterparts, whereas both subsets have similar IFN-γ responses. We further demonstrate that the CD16-dependent degranulation pathway, but not antibody-dependent cell-mediated cytotoxicity, contribute to the superior cytotoxicity of CD56(+) Vγ9Vδ2 T cells. Our study provides further evidence for the phenotypic and functional characterization of human Vγ9Vδ2 T-cell subsets during fluA virus infection and may help improve the γδ T-cell-based immunotherapy for viral infection.

The Extent of Hearing Input Affects the Plasticity of the Auditory Cortex in Children With Hearing Loss: A Preliminary Study.

PURPOSE: This study investigated to what extent residual hearing and rehabilitation options (e.g., hearing aids [HAs]) affect the auditory cortex in children with hearing loss. METHOD: Twenty-one children with bilateral congenital sensorineural hearing loss who were candidates for cochlear implantation were recruited. Voxel-based morphometry analysis was conducted to assess the gray matter (GM) volume in the auditory cortex. Children's residual hearing was measured by pure-tone audiometry at different frequencies. Multiple linear regression models were conducted to examine the effects of residual hearing and the use of HAs on GM volume in the auditory cortex with the control of age and gender. RESULTS: Children with more residual hearing at high frequencies had larger GM volume ratio (corrected by total intracranial volume) in the left Heschl's gyrus (r = -.545, p = .013). An interaction effect between residual hearing and the use of HAs suggested that the effect of residual hearing on GM ratio was moderated by the use of HAs (ß = -.791, p = .020). Compared with children with less residual hearing, children who had more residual hearing benefited more from longer use of HAs in terms of a larger GM ratio. CONCLUSIONS: Our preliminary findings highlight the impact of residual hearing on the neuroanatomy of the auditory cortex in children with hearing loss. Moreover, our results call for more auditory input via HAs for children with more residual hearing to preserve the auditory cortex before cochlear implantation. For children with less residual hearing who might receive limited benefit from HAs, an early cochlear implant would be necessary.

Corrigendum: A Chinese medicine formula (Bushen Huoxue Tongluo) for the treatment of chronic subjective tinnitus: a study protocol for a pilot, assessor-blinded, randomized clinical trial.

[This corrects the article DOI: 10.3389/fphar.2022.844730.].

Type 1 responses of human Vγ9Vδ2 T cells to influenza A viruses.

γδ T cells are essential constituents of antimicrobial and antitumor defenses. We have recently reported that phosphoantigen isopentenyl pyrophosphate (IPP)-expanded human Vγ9Vδ2 T cells participated in anti-influenza virus immunity by efficiently killing both human and avian influenza virus-infected monocyte-derived macrophages (MDMs) in vitro. However, little is known about the noncytolytic responses and trafficking program of γδ T cells to influenza virus. In this study, we found that Vγ9Vδ2 T cells expressed both type 1 cytokines and chemokine receptors during influenza virus infection, and IPP-expanded cells had a higher capacity to produce gamma interferon (IFN-γ). Besides their potent cytolytic activity against pandemic H1N1 virus-infected cells, IPP-activated γδ T cells also had noncytolytic inhibitory effects on seasonal and pandemic H1N1 viruses via IFN-γ but had no such effects on avian H5N1 or H9N2 virus. Avian H5N1 and H9N2 viruses induced significantly higher CCL3, CCL4, and CCL5 production in Vγ9Vδ2 T cells than human seasonal H1N1 virus. CCR5 mediated the migration of Vγ9Vδ2 T cells toward influenza virus-infected cells. Our findings suggest a novel therapeutic strategy of using phosphoantigens to boost the antiviral activities of human Vγ9Vδ2 T cells against influenza virus infection.

A Chinese Medicine Formula (Bushen Huoxue Tongluo) for the Treatment of Chronic Subjective Tinnitus: A Study Protocol for a Pilot, Assessor-Blinded, Randomized Clinical Trial.

Background: Tinnitus is a common problem worldwide. There is still no effective method to cure it. Traditional Chinese medicine (TCM) may be a potentially effective treatment approach for tinnitus. However, there is still no clinical trial with scientifically rigorous methodology to evaluate the treatment effect of TCM for tinnitus. Therefore, we propose a pilot study to inform the feasibility of a future full-scale RCT to establish the efficacy of TCM formula for tinnitus. Objectives: The aim of this study is to determine the feasibility of a full-scale RCT and explore whether a TCM formula (BHT) has an additional effect on improving tinnitus when compared to informative counseling alone. Design: An assessor-blinded, randomized, controlled clinical trial is used. Participants: Twenty-four patients with chronic subjective tinnitus will be enrolled. Interventions: The patients will be allocated randomly to receive a TCM formula (BHT, Bushen Huoxue Tongluo) and informative counseling or informative counseling alone. The oral BHT herbal granules will be taken twice per day continuously for 8 weeks. Main outcome measures: The primary outcomes include recruitment rate, intervention completion rate, and data completion rate to evaluate the feasibility. The secondary outcomes include Tinnitus Handicap Inventory, tinnitus functional index, tinnitus sensation level, self-rated visual analogue scale on tinnitus loudness and annoyance, Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, and adverse event. The outcome measures will be collected at baseline, end of treatment, and 4-week follow-up. Discussion: This trial is currently ongoing and is recruiting patients. The expected study results will find some preliminary evidence about the clinical effectiveness of BHT on chronic tinnitus and will also determine if it is feasible to conduct a full-scale RCT of BHT and identify the necessary changes to the protocol if possible.

Clinical Performance, Safety, and Patient-Reported Outcomes of an Active Osseointegrated Steady-State Implant System.

OBJECTIVE: To investigate the clinical performance, safety, and patient-reported outcomes of an active osseointegrated steady-state implant system that uses piezoelectric technology. STUDY DESIGN: A prospective, multicenter, open-label, single-arm, within-subject clinical investigation. SETTING: Three tertiary referral clinical centers located in Melbourne, Sydney, and Hong Kong. PATIENTS: Twenty-nine adult subjects, 24 with mixed hearing loss or conductive hearing loss and 5 with single-sided sensorineural deafness. INTERVENTION: Implantation with the Cochlear Osia 2 System. MAIN OUTCOME MEASURES: Audiological threshold evaluation and speech recognition in quiet and in noise. Patient satisfaction and safety. RESULTS: At 6-month follow-up after surgery, a mean improvement in pure-tone average of 26.0 dB hearing level and a mean improvement of 8.8 dB signal-to-noise ratio in speech reception threshold in noise was achieved with the investigational device as compared with the unaided situation. Usability of the investigational device was rated 71.4/100 mm for sound processor retention and 81.4/100 mm for overall comfort using a visual analog scale. CONCLUSION: These outcomes confirm the clinical safety, performance, and benefit of an innovative active transcutaneous bone conduction implant using a piezoelectric transducer design in subjects with conductive hearing loss, mixed hearing loss, or single-sided sensorineural deafness.

Comparing Early Pragmatics in Typically Developing Children and Children with Neurodevelopmental Disorders.

This study examined the early pragmatic language skills in typically developing (TD) preschool-age children, children with language impairment (LI) and children with autism spectrum disorder (ASD). Two hundred and sixty-two TD children, 73 children with LI, and 16 children with ASD were compared on early pragmatics through direct assessment (DA). Post hoc analysis revealed that children in two clinical groups displayed significant pragmatic language deficits. Children in the ASD group who were older exhibited comparable degree of impairments as their LI peers, suggesting a relatively stagnant development of pragmatic language skills in children with ASD. Findings also supported the use of DA in identifying pragmatic language deficits, which have implications for the adoption of this assessment approach in clinical settings.

Induction of proinflammatory cytokines in primary human macrophages by influenza A virus (H5N1) is selectively regulated by IFN regulatory factor 3 and p38 MAPK.

The hyperinduction of proinflammatory cytokines and chemokines such as TNF-alpha, IFN-beta, and CCL2/MCP-1 in primary human macrophages and respiratory epithelial cells by the highly pathogenic avian influenza H5N1 is believed to contribute to the unusual severity of human H5N1 disease. Here we show that TNF-alpha, IFN-beta, and IFN-lambda1 are the key mediators directly induced by the H5N1 virus in primary human macrophages. In comparison with human influenza (H1N1), the H5N1 virus more strongly activated IFN regulatory factor 3 (IRF3). IRF3 knockdown and p38 kinase inhibition separately and in combination led to a substantial reduction of IFN-beta, IFN-lambda1, and MCP-1 but only to a partial reduction of TNF-alpha. IRF3 translocation was independent of p38 kinase activity, indicating that IRF3 and p38 kinase are distinct pathways leading to cytokine production by H5N1 virus. We conclude that IRF3 and p38 kinase separately and predominantly contribute to H5N1-mediated induction of IFN-beta, IFN-lambda1, and MCP-1 but only partly control TNF-alpha induction. A more precise identification of the differences in the regulation of TNF-alpha and IFN-beta could provide novel targets for the design of therapeutic strategies for severe human H5N1 influenza and also for treating other causes of acute respiratory distress syndrome.

Efficacy of Phase 1 of Life Goals Programme on symptom reduction and mood stability for bipolar disorder.

BACKGROUND: Life Goals Programme (LGP) was developed as a psychological intervention for bipolar disorder, with its structured 6-session psychoeducation phase (Phase 1) targeting understanding of the disorder, medication adherence, early warning signs, and coping with symptoms and triggers. The present study tested the efficacy of Phase 1 of the LGP on symptom recovery and moment-by-moment mood stability, as well as medication adherence and quality of life. METHODS: Adults with bipolar disorder were randomly allocated to the LGP condition (six weekly group sessions) or the waitlist condition (six weeks of standard care, followed by the same LGP intervention). Participants were assessed before and after treatment, and at 6-month follow up. Waitlist participants were additionally assessed at baseline. Assessment included a clinical interview (SCID, MADRS, YMRS, and HAM-A), self-reported questionnaires, and 6-day experience sampling assessment on a mobile device. RESULTS: 64 out-patients with bipolar disorder (44 Bipolar I and 20 Bipolar II subtypes) participated in this study. LGP was well received and attended. Following LGP, there were significant improvements in knowledge about illness and level of anxiety, which were of large effect sizes and sustained at 6-month follow-up. Experience sampling assessment revealed small but significant improvements in moment-by-moment mood stability. Improvement in medication adherence was significant at 6 months and was of a moderate-to-large effect size. Changes in anxiety and mood stability were significantly greater following LGP than standard care. LIMITATIONS: Our results warrant further testing against active control. CONCLUSIONS: There was a robust improvement in emotional regulation following the 6-week LGP.

Moment-to-moment interaction between affectivity and coping behaviours in bipolar disorder and the role of cognitive appraisals.

BACKGROUND: Individuals with bipolar disorder respond to affective symptoms with a range of coping behaviours, which may further maintain the symptoms. AIMS: To examine moment-to-moment dynamics between affective states and coping behaviours, and to evaluate the role of cognitive appraisals of internal states as moderators. METHOD: Forty-six individuals with bipolar disorder completed a clinical interview and an experience sampling assessment over 6 days. Time-lagged analyses were conducted by multilevel regression modelling. RESULTS: A total of 1807 momentary entries were analysed. Negative affect predicted an increase in rumination at the subsequent time point (ß = 0.21, s.e. = 0.08, P = 0.009, 95% CI 0.05-0.36), and vice versa (ß = 0.03, s.e. = 0.01, P = 0.009, 95% CI 0.01-0.05). Positive affect predicted an increase in adaptive coping (ß = 0.26, s.e. = 0.11, P = 0.018, 95% CI 0.04-0.47), and vice versa (ß = 0.02, s.e. = 0.01, P = 0.019, 95% CI 0.00-0.03). Positive affect also predicted a decrease in rumination (ß = -0.15, s.e. = 0.06, P = 0.014, 95% CI -0.26 to -0.03), and vice versa (ß = -0.03, s.e. = 0.01, P = 0.016, 95% CI -0.06 to -0.01). Extreme cognitive appraisals predicted stronger associations between affective states and coping behaviours. CONCLUSIONS: Feedback loops between affective states and coping behaviours were revealed in the daily life of individuals with bipolar disorder, which were moderated by extreme cognitive appraisals. DECLARATION OF INTEREST: None.

The development of Cantonese Lexical Neighborhood Test: a pilot study.

OBJECTIVE: This study aimed at developing a theoretically driven open-set speech recognition test for pediatric clinical population of cochlear implant and/or hearing aid users, with Cantonese Chinese as their first language, to track progress in speech recognition performance as an outcome measurement of their rehabilitation. METHODS: Six monosyllabic and six disyllabic word lists were generated from the Cantonese CHILDES language database, constructed according to the Neighborhood Activation Model. There were three lexically "easy" and three lexically "hard" word lists in each sub-test, with 25 items in each list. Four pediatric cochlear implant users and 10 hearing aid users, with bilateral congenital severe to profound sensorineural hearing impairment and below the age of 10, participated in the study. Their performances on word recognition and phoneme recognition with the new test lists, as well as the inter-list equivalency, inter-rater reliability, and face validity of the new materials, were investigated. RESULTS: Word recognition was higher among disyllables than monosyllables. Lexically "easy" disyllabic words were better recognized than their "hard" counterparts and the monosyllables. No significant difference was noted among the three lists in each combination of syllable structure and lexical property. High inter-rater reliability, as well as high correlation between Cantonese LNT score and a receptive vocabulary test score, were revealed. CONCLUSIONS: These newly developed test lists provided reliable information on spoken word recognition of pediatric hearing prosthesis users with severe to profound hearing impairment. Inter-list equivalency and inter-rater reliability allowed monitoring of rehabilitation progress on such specific pediatric clinical population with this new test. (255).

Hearing loss in Chinese school children with Down syndrome.

OBJECTIVE: There is well-documented evidence in the literature concerning a high prevalence of deafness in children with Down syndrome (DS). The aim of this study was to examine the extent of hearing impairment and address the rehabilitation needs of a Chinese population with DS who were either in special schools or integrated into mainstream schools. METHODS: This study screened 92 children with DS at their own schools and 11 were reassessed in the University of Hong Kong Hearing Centre. Hearing status of the children with DS was analyzed on the basis of their screening and reassessment results for tympanometric, transient evoked otoacoustic emission (TEOAE) and pure tone audiometric examinations. RESULTS: A high point prevalence of hearing impairment (78% by ears or 90% by participants) in a Chinese school-aged sample of children with DS was noted. The most common degree of loss was mild to moderate. No significant gender difference, age effect or ear asymmetry was found for tympanometric failure or absence of TEOAE. An unfavorable mean speech intelligibility index score (0.2) was found for this group of children. CONCLUSIONS: Sound field amplification and suitable acoustic modifications to classrooms were recommended for Chinese children with DS in Hong Kong to improve their listening and learning environment. The point prevalence of hearing impairment in older children with DS in this study was in contrast to a previous local study on a younger age group. Further effort is needed to determine the role of possible aging effects on the type and prevalence of hearing impairment in populations with DS.

An Application of Item Response Theory and the Rasch Model in Speech Recognition Test Materials.

PURPOSE: The purpose of this study was to describe an attempt to apply item-response theory (IRT) and the Rasch model to construction of speech-recognition tests. A set of word-recognition test items applicable to children as young as 3 years old-with any level of hearing sensitivity, with or without using hearing devices-was developed. METHOD: Test items were constructed through expert consultation and by reference to some established language corpora, validated with 121 participants with various degrees of hearing loss and 255 with typical hearing. IRT and the Rasch model were applied to evaluate item quality. RESULTS: Eighty disyllabic word items were selected in accordance with IRT. The speech-recognition abilities of the 376 young participants are reported. The IRT analyses on this set of data are also discussed. CONCLUSIONS: A new set of speech-recognition test materials in Cantonese Chinese has been developed. Construction of short equivalent lists may be performed in accordance with IRT item qualities. Clinical applications of this test tool in the particular language population are discussed.

Evaluation of the ClearVoice Strategy in Adults Using HiResolution Fidelity 120 Sound Processing.

OBJECTIVES: This study aimed to evaluate the benefits of ClearVoice strategy on speech perception in noise and in everyday listening situations in Cantonese-speaking cochlear implant users. METHODS: Twelve experienced adult users of the Harmony implant and HiRes 120 sound processing participated in the study. The study employed a prospective within-subjects design wherein speech recognition in adults using HiRes 120 without ClearVoice turned on (control option) was compared to their performance with HiRes 120 with ClearVoice turned on. Each subject was evaluated with two different ClearVoice gain settings: -12 dB (ClearVoice medium) and -18 dB (ClearVoice high) after one-week of use. The Cantonese hearing in noise test and a questionnaire were used as the outcome measures. RESULTS: Subjects performed significantly better with ClearVoice medium than with control option in noise. No significant difference in performance was noted among the 3 settings in quiet. Most subjects reported high level of satisfaction with ClearVoice in daily listening situations and preferred to keep ClearVoice on. CONCLUSION: ClearVoice can help cochlear implant recipients to hear better in noise.

Characterization of a novel gyrovirus in human stool and chicken meat.

BACKGROUND: Sequence-independent amplification of clinical specimens can lead to the identification of novel pathogens. OBJECTIVES: To identify novel viruses in human stool specimens from patients with diarrhea and to investigate the ecology and clinical significance of such viruses. STUDY DESIGN: Nucleic acid extracted from stool specimens from patients with diarrhea with no known etiology were subjected to random PCR amplification and Roche/454 pyrosequencing. Novel viruses identified were genetically and epidemiologically characterized. RESULTS: Four gyroviruses, chicken anemia virus (CAV), human gyrovirus (HGV)/avian gyrovirus 2 (AGV2), gyrovirus 3 (GyV3) and a novel gyrovirus (tentatively designated as gyrovirus 4 (GyV4)) were identified in human stool specimens. GyV4, as well as CAV and AGV2/HGV were also detected in chicken skin and meat used for human consumption. CONCLUSIONS: A novel gyrovirus (GyV4) was identified in human stool and in chicken meat sold for human consumption. This virus was phylogenetically distinct from previously reported gyroviruses in chicken and humans (chicken anemia virus, human gyrovirus, avian gyrovirus 2 and recently reported gyrovirus 3). The epidemiology and pathogenesis of this virus in humans and in chicken needs to be further investigated.

The aminobisphosphonate pamidronate controls influenza pathogenesis by expanding a gammadelta T cell population in humanized mice.

There are few antiviral drugs for treating influenza, and the emergence of antiviral resistance has further limited the available therapeutic options. Furthermore, antivirals are not invariably effective in severe influenza, such as that caused by H5N1 viruses. Thus, there is an urgent need to develop alternative therapeutic strategies. Here, we show that human Vγ9Vδ2 T cells expanded by the aminobisphosphonate pamidronate (PAM) kill influenza virus-infected cells and inhibit viral replication in vitro. In Rag2(-/-)γc(-/-) immunodeficient mice reconstituted with human peripheral mononuclear cells (huPBMCs), PAM reduces disease severity and mortality caused by human seasonal H1N1 and avian H5N1 influenza virus, and controls the lung inflammation and viral replication. PAM has no such effects in influenza virus-infected Rag2(-/-)γc(-/-) mice reconstituted with Vγ9Vδ2 T cell-depleted huPBMCs. Our study provides proof-of-concept of a novel therapeutic strategy for treating influenza by targeting the host rather than the virus, thereby reducing the opportunity for the emergence of drug-resistant viruses. As PAM has been commonly used to treat osteoporosis and Paget's disease, this new application of an old drug potentially offers a safe and readily available option for treating influenza.