Socioeconomic and ethnic disparities associated with access to cochlear implantation for severe-to-profound hearing loss: A multicentre observational study of UK adults.

BACKGROUND: Patients with severe-to-profound hearing loss may benefit from management with cochlear implants. These patients need a referral to a cochlear implant team for further assessment and possible surgery. The referral pathway may result in varied access to hearing healthcare. This study aimed to explore referral patterns and whether there were any socioeconomic or ethnic associations with the likelihood of referral. The primary outcome was to determine factors influencing referral for implant assessment. The secondary outcome was to identify factors impacting whether healthcare professionals had discussed the option of referral. METHODS AND FINDINGS: A multicentre multidisciplinary observational study was conducted in secondary care Otolaryngology and Audiology units in Great Britain. Adults fulfilling NICE (2019) audiometric criteria for implant assessment were identified over a 6-month period between 1 July and 31 December 2021. Patient- and site-specific characteristics were extracted. Multivariable binary logistic regression was employed to compare a range of factors influencing the likelihood of implant discussion and referral including patient-specific (demographics, past medical history, and degree of hearing loss) and site-specific factors (cochlear implant champion and whether the hospital performed implants). Hospitals across all 4 devolved nations of the UK were invited to participate, with data submitted from 36 urban hospitals across England, Scotland, and Wales. Nine hospitals (25%) conducted cochlear implant assessments. The majority of patients lived in England (n = 5,587, 86.2%); the rest lived in Wales (n = 419, 6.5%) and Scotland (n = 233, 3.6%). The mean patient age was 72 ± 19 years (mean ± standard deviation); 54% were male, and 75·3% of participants were white, 6·3% were Asian, 1·5% were black, 0·05% were mixed, and 4·6% were self-defined as a different ethnicity. Of 6,482 submitted patients meeting pure tone audiometric thresholds for cochlear implantation, 311 already had a cochlear implant. Of the remaining 6,171, 35.7% were informed they were eligible for an implant, but only 9.7% were referred for assessment. When adjusted for site- and patient-specific factors, stand-out findings included that adults were less likely to be referred if they lived in more deprived area decile within Indices of Multiple Deprivation (4th (odds ratio (OR): 2·19; 95% confidence interval (CI): [1·31, 3·66]; p = 0·002), 5th (2·02; [1·21, 3·38]; p = 0·05), 6th (2·32; [1·41, 3·83]; p = 0.05), and 8th (2·07; [1·25, 3·42]; p = 0·004)), lived in London (0·40; [0·29, 0·57]; p < 0·001), were male (females 1·52; [1·27, 1·81]; p < 0·001), or were older (0·97; [0·96, 0·97]; p < 0·001). They were less likely to be informed of their potential eligibility if they lived in more deprived areas (4th (1·99; [1·49, 2·66]; p < 0·001), 5th (1·75; [1·31, 2·33], p < 0·001), 6th (1·85; [1·39, 2·45]; p < 0·001), 7th (1·66; [1·25, 2·21]; p < 0·001), and 8th (1·74; [1·31, 2·31]; p < 0·001) deciles), the North of England or London (North 0·74; [0·62, 0·89]; p = 0·001; London 0·44; [0·35, 0·56]; p < 0·001), were of Asian or black ethnic backgrounds compared to white patients (Asian 0·58; [0·43, 0·79]; p < 0·001; black 0·56; [0·34, 0·92]; p = 0·021), were male (females 1·46; [1·31, 1·62]; p < 0·001), or were older (0·98; [0·98, 0·98]; p < 0·001). The study methodology was limited by its observational nature, reliance on accurate documentation of the referring service, and potential underrepresentation of certain demographic groups. CONCLUSIONS: The majority of adults meeting pure tone audiometric threshold criteria for cochlear implantation are currently not appropriately referred for assessment. There is scope to target underrepresented patient groups to improve referral rates. Future research should engage stakeholders to explore the reasons behind the disparities. Implementing straightforward measures, such as educational initiatives and automated pop-up tools for immediate identification, can help streamline the referral process.

A scoping review on the clinical effectiveness of Trans-Impedance Matrix (TIM) measurements in detecting extracochlear electrodes and tip fold overs in Cochlear Ltd devices.

BACKGROUND: Extrusion of electrodes outside the cochlea and tip fold overs may lead to suboptimal outcomes in cochlear implant (CI) recipients. Intraoperative measures such as Trans-Impedance Matrix (TIM) measurements may enable clinicians to identify electrode malposition and direct surgeons to correctly place the electrode array during surgery. OBJECTIVES: To assess the current literature on the effectiveness of TIM measurements in identifying extracochlear electrodes and tip fold overs. METHODS: A scoping review of studies on TIM-based measurements were carried out using the Databases-Medline/PubMed, AMED, EMBASE, CINAHL and the Cochrane Library following PRISMA guidelines. Eleven full texts articles met the inclusion criteria. Only human studies pertaining to TIM as a tool used in CI were included in the review. Further, patient characteristics, electrode design, and TIM measurement outcomes were reported. RESULTS: TIM measurements were available for 550 implanted ears with the subjects age ranged between 9 months to 89 years. Abnormal TIM measurements were reported for 6.55% (36). Tip fold over was detected in 3.64% (20) of the cases, extracochlear electrodes in 1.45% (8), and 1.45% (8) were reported as buckling. Slim-modiolar electrode array designs were more common (54.71%) than pre-curved (23.34%) or lateral wall (21.95%) electrode array. Abnormal cochlear anatomy was reported for five ears (0.89%), with normal cochlear anatomy for all other patients. CONCLUSION: TIM measurement is a promising tool for the intraoperative detection of electrode malposition. TIM measurement has a potential to replace intraoperative imaging in future. Though, TIM measurement is in its early stages of clinical utility, intuitive normative data sets coupled with standardised criteria for detection of abnormal electrode positioning would enhance its sensitivity.

A systematic review of otologic injuries sustained in civilian terrorist explosions.

PURPOSE: Determine the prevalence of otological symptoms and tympanic membrane perforation, healing rates of tympanic membrane perforation with surgical and conservative management, and hearing function in civilian victims of terrorist explosions. METHODS: A systematic review was conducted with searches on Medline, Embase, EMCare and CINAHL for publications between the 1st January 1945 and 26th May 2023. Studies with quantitative data addressing our aims were included. This review is registered with PROSPERO: CRD42020166768. Among 2611 studies screened, 18 studies comprising prospective and retrospective cohort studies were included. RESULTS: The percentage of eardrums perforated in patients admitted to hospital, under ENT follow up and attending the emergency department is 69.0% (CI 55.5-80.5%), 38.7% (CI 19.0-63.0%, I2 0.715%) and 21.0% (CI 11.9-34.3%, I2 0.718%) respectively. Perforated eardrums heal spontaneously in 62.9% (CI 50.4-73.8%, I2 0.687%) of cases and in 88.8% (CI 75.9-96.3%, I2 0.500%) of cases after surgery. Common symptoms present within one month of bombings are tinnitus 84.7% (CI 70.0-92.9%, I2 0.506%), hearing loss 83.0% (CI 64.5-92.9%, I2 0.505%) and ear fullness 59.7% (CI 13.4-93.4%, I2 0.719). Symptomatic status between one and six months commonly include no symptoms 57.5% (CI 46.0-68.3%), hearing loss 35.4% (CI 21.8-51.8%, I2 0.673%) and tinnitus 15.6% (CI 4.9-40.0%, I2 0.500%). Within one month of bombings, the most common hearing abnormality is sensorineural hearing loss affecting 26.9% (CI 16.9-40.1%, I2 0.689%) of ears 43.5% (CI 33.4-54.2%, I2 0.500) of people. CONCLUSION: Tympanic membrane perforation, subjective hearing loss, tinnitus, ear fullness and sensorineural hearing loss are common sequelae of civilian terrorist explosions.

Digital thErapy For Improved tiNnitus carE Study (DEFINE): Protocol for a randomised controlled trial.

Tinnitus is a common health condition, affecting approximately 15% of the UK population. The tinnitus treatment with the strongest evidence base is Cognitive Behavioural Therapy (CBT), with standard tinnitus therapy typically augmented with education, relaxation and other techniques. Availability of CBT and conventional tinnitus therapy more broadly is limited for tinnitus sufferers. The DEFINE trial aims to assess whether smartphone-delivered tinnitus therapy, the Oto app, is as effective as current standard care, one-to-one therapist-delivered tinnitus treatment for the treatment of tinnitus in adults. The trial is registered in the ISRCTN Registry: ISRCTN99577932. DEFINE is an open-label, non-inferiority, prospective, parallel design, randomised-controlled trial. Recruitment, interventions and assessments will be remote, enabling UK-wide participant involvement. 198 participants aged 18 years or more will be recruited via social media advertisement or via primary care physicians. A screening process will identify those with tinnitus that impacts health-related quality of life, and following consent smartphone-based audiometry will be performed. Randomisation 1:1 to the Oto app or one-to-one therapist-led tinnitus therapy will be performed centrally by computer, matching groups for age, sex and hearing level. Following participant allocation, the Oto app will be provided for immediate use, or a one-to-one remote therapy appointment booked to occur within approximately 1 week, with up to 6 sessions delivered. Participant outcomes will be collected at 4,12, 26 and 52 weeks via questionnaire and phone call. The primary outcome is the change in Tinnitus Functional Index (TFI) total score measured at 26 weeks following allocation. Adverse events will be recorded. A health economic evaluation in the form of a cost-utility analysis will be performed using data from participant submitted EuroQol 5D-5L and Health Utilities Index Mark 3 scores and resource use data. Trial results will be made publicly available, including a plain English summary.

The effect of photobiomodulation on hearing loss: A systematic review.

OBJECTIVES: To assess outcomes associated with photobiomodulation therapy (PBMT) for hearing loss in human and animal studies. DESIGN: Systematic review and narrative synthesis in accordance with PRISMA guidelines. SETTING: Data bases searched: MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov and Web of Science. No limits were placed on language or year of publication. Review conducted in accordance with the PRISMA 2020 statement. PARTICIPANTS: All human and animal subjects treated with PBMT for hearing loss. MAIN OUTCOME MEASURES: Pre- and post-PBMT audio metric outcomes. RESULTS: Searches identified 122 abstracts and 49 full text articles. Of these, 17 studies met the inclusion criteria, reporting outcomes in 327 animals (11 studies), 30 humans (1 study), and 40 animal specimens (5 studies). PBMT parameters included 6 different wavelengths: 908 nm (1 study), 810 nm (1 study), 532 & 635 nm (1 study), 830 nm (3 studies), 808 nm (11 studies). The duration ranged from 4 to 60 minutes in a session, and the follow-up ranged from 5-28 days. Outcomes improved significantly when wavelengths within the range of 800-830 nm were used, and with greater duration of PBMT exposure. Included studies predominantly consisted of non-randomized controlled trials (10 studies). CONCLUSIONS: Hearing outcomes following PBMT appear to be superior to no PBMT for subjects with hearing loss, although higher level evidence is required to verify this. PBMT enables concentrated, focused delivery of light therapy to the inner ear through a non-invasive manner with minimal side effects. As a result of heterogeneity in reporting PBMT parameters and outcomes across the included studies, direct comparison is challenging.

Outcomes of cochlear implantation in Usher syndrome: a systematic review.

PURPOSE: This study is a systematic review of the literature which seeks to evaluate auditory and quality of life (QOL) outcomes of cochlear implantation in patients with Usher syndrome. METHODS: Systematic review of studies indexed in Medline via PubMed, Ovid EMBASE, Web of Science, CENTRAL and clinicaltrials.gov was performed up to March 9th 2022, conducted in accordance with the PRISMA statement. Patient demographics, comorbidity, details of cochlear implantation, auditory, and QOL outcomes were extracted and summarized. RESULTS: 33 studies reported over 217 cochlear implants in 187 patients with Usher syndrome, comprising subtypes 1 (56 patients), 2 (9 patients), 3 (23 patients), and not specified (99 patients). Auditory outcomes included improved sound detection, speech perception, and speech intelligibility. QOL outcomes were reported for 75 patients, with benefit reported in the majority. CONCLUSIONS: Many patients with Usher syndrome develop improved auditory outcomes after cochlear implantation with early implantation being an important factor.

Early activation of cochlear implants: a systematic review and narrative synthesis.

BACKGROUND: Device activation typically occurs four weeks post cochlear implant surgery. Emerging evidence suggests earlier activation is feasible and beneficial, giving patients quicker access to sound and rehabilitation. OBJECTIVES: Assess current literature for effects of early cochlear implant activation. METHODS: Electronic searches of Medline/PubMed, AMED, EMBASE, CINAHL and the Cochrane Library following PRISMA guidelines. Studies investigating any aspect of early activation were included for review. RESULTS: From 15 studies, 625 patients received early activation, compared with 243 patients in the control groups. Early activation was considered as within 7 days post-operatively with 12 studies reporting within 1 day post-operatively, compared with standard activation of 9-46 days post-operatively in the control group. Some studies indicated earlier low levels of impedance in the early activation group. Magnet strength adjustment or off-ear processor wear was often recommended within the early activation cohort. Complication rates were low in both groups. Early activation improved patient satisfaction and anxiety levels without detriment to speech recognition or rehabilitation. CONCLUSION: Early cochlear implant activation is feasible and allows patients with no contraindications, earlier access to auditory perception and rehabilitation and reduces anxiety linked to delay in activation. Further evidence is required to monitor long-term effects of early activation.

The effect of photobiomodulation on tinnitus: a systematic review.

OBJECTIVE: To establish outcomes following photobiomodulation therapy for tinnitus in humans and animal studies. METHODS: A systematic review and narrative synthesis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The databases searched were: Medline, Embase, Cochrane Central Register of Controlled Trials ('Central'), ClinicalTrials.gov and Web of Science including the Web of Science Core collection. There were no limits on language or year of publication. RESULTS: The searches identified 194 abstracts and 61 full texts. Twenty-eight studies met the inclusion criteria, reporting outcomes in 1483 humans (26 studies) and 34 animals (2 studies). Photobiomodulation therapy parameters included 10 different wavelengths, and duration ranged from 9 seconds to 30 minutes per session. Follow up ranged from 7 days to 6 months. CONCLUSION: Tinnitus outcomes following photobiomodulation therapy are generally positive and superior to no photobiomodulation therapy; however, evidence of long-term therapeutic benefit is deficient. Photobiomodulation therapy enables concentrated, focused delivery of light therapy to the inner ear through a non-invasive manner, with minimal side effects.

Nasopharyngeal Carcinoma: Case Presentation and Literature Review of Treatment Innovation with Immunotherapy.

Nasopharyngeal carcinoma (NPC), a rare head and neck malignancy, arises from the epithelial lining of nasopharyngeal mucosa. The confluence of various risk factors, such as latent Epstein-Barr virus infection, genetic susceptibility, smoking, alcohol consumption, and high nitrosamine diet, is thought to contribute to NPC pathogenesis. Radiation therapy serves as the mainstay of treatment for early stage while concurrent chemotherapy and radiation are the basis of treatment for locoregional advanced disease with overall 80% five-year survival rate. Recurrent or metastatic disease pose treatment challenges as reirradiation, repeat cycles of chemotherapy, and surgery follow with high likelihood of treatment toxicity or postoperative morbidities. Typically reserved for nonresectable recurrent or metastatic disease, immunotherapy serves as novel treatment for NPC. NPC tumor microenvironment predominated by a dense infiltrate of immune cells hosts an ideal target for immunotherapy. Several clinical trials have investigated the efficacy of anti-programmed cell death protein 1 antibodies such as pembrolizumab, nivolumab, and camrelizumab with promising results. Treatment of recurrent and metastatic NPC remains a challenge; however, the advent of immunotherapy has provided additional options and potential for preventative and therapeutic measures.

Outcomes of Cochlear implantation in early-deafened patients with Waardenburg syndrome: A systematic review and narrative synthesis.

Objective: This systematic review aims to establish the expected hearing and speech outcomes following cochlear implantation (CI) in patients with profound congenital deafness secondary to Waardenburg syndrome (WS). Methods: A systematic review of the literature and narrative synthesis was performed in accordance with the PRISMA statement. Databases searched: Medline, Pubmed, Embase, Web of Science, Cochrane Collection, and ClinicalTrials.gov. No limits were placed on language or year of publication. Results: Searches identified 186 abstracts and full texts. Of these, 16 studies met inclusion criteria reporting outcomes in 179 patients and at least 194 implants. Hearing outcomes of those receiving cochlear implantation were generally good. Five studies included genetic analysis of one or more of the participants. A total of 11 peri/post-operative complications were reported. The methodological quality of included studies was modest, mainly comprising noncontrolled case series with small cohort size. All studies were OCEBM grade III-IV. Conclusion: Cochlear implantation in congenitally deafened children with Waardenburg Syndrome is a well-established intervention as a method of auditory rehabilitation. Due to the uncommon nature of the condition, there is a lack of large-scale high-quality studies examining the use of cochlear implantation in this patient group. However, overall outcomes following implantation are positive with the majority of patients demonstrating improved audiometry, speech perception and speech intelligibility supporting its use in appropriately selected cases.

A Phase II Trial of Rivoceranib, an Oral Vascular Endothelial Growth Factor Receptor 2 Inhibitor, for Recurrent or Metastatic Adenoid Cystic Carcinoma.

PURPOSE: This open-label, single-arm, phase II study evaluated the vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase inhibitor (TKI) rivoceranib in patients with recurrent or metastatic (R/M) adenoid cystic carcinoma (ACC). PATIENTS AND METHODS: Eligible patients had confirmed disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) with ≥20% increase in radiologically or clinically measurable lesions or appearance of new lesions within the preceding 6 months. Patients received oral rivoceranib 700 mg once daily. Primary outcomes were objective response rate (ORR) by investigator review and by blinded independent review committee (BIRC). RESULTS: Eighty patients were enrolled and 72 were efficacy evaluable. Seventy-four patients had distant metastases and 49 received prior systemic treatment (14 received VEGFR TKIs). Per investigator and BIRC, respectively, ORR was 15.3% [95% confidence interval (95% CI), 7.9-25.7] and 9.7% (95% CI, 4.0-19.0); median duration of response was 14.9 months (95% CI, 4.9-17.3) and 7.2 months (95% CI, 3.5-8.4); and median progression-free survival was 9.0 months (95% CI, 7.3-11.5) and 9.0 months (95% CI, 7.7-11.5). Grade ≥3 treatment-related adverse events occurred in 56 patients (70.0%); the most common were hypertension (34, 42.5%) and stomatitis (6, 7.5%). Four grade 5 events occurred with one attributed to rivoceranib (epistaxis). Sixty-eight patients (85.0%) had ≥1 dose modifications and 16 patients (20.0%) discontinued rivoceranib for toxicity. CONCLUSIONS: In patients with progressing R/M ACC, rivoceranib demonstrated antitumor activity and a manageable safety profile consistent with other VEGFR TKIs.

Antibiotics versus non-antibiotic treatments for acute otitis externa: A systematic review and meta-analysis.

BACKGROUND: Otitis externa is a condition causing inflammation of the outer ear canal, which presents with itching, discharge and pain. Most cases of acute otitis externa are caused by bacterial infection and are thus treated with antibiotics. This systematic review and meta-analysis of randomised controlled trials aims to assess the effectiveness of topical non-antibiotic treatments compared to topical antibiotic treatment for the treatment of acute otitis externa. METHODS: Systematic review and meta-analysis databases searched: Cochrane Library including ClinicalTrials.gov; MEDLINE; World Health Organisation International Clinical Trials Registry Platform and Web of Science to identify randomised clinical trials evaluating topical antibiotics and topical non-antibiotic agents in adults and children with acute otitis externa. Non-antibiotic therapeutics for comparison with topical antibiotics included antiseptics, steroids, non-pharmaceuticals and astringents. RESULTS: Seventeen trials were eligible for inclusion, with 10 combined in meta-analysis. Data could be pooled comparing antiseptic and steroid monotherapies with topical antibiotic agents. There were no significant differences in cure rates in any pairwise comparisons. Individually, the majority of studies favoured topical antiseptics or steroids over antibiotics, however these differences were not significant when pooled in meta-analysis. CONCLUSION: Antiseptic, steroid and antibiotic monotherapies are all effective for the management of acute otitis externa. There is insufficient evidence to suggest that topical antiseptic or steroid agents are superior or inferior to topical antibiotics.

Hearing Health Care Stakeholders' Perspectives on Teleaudiology Implementation: Lessons Learned During the COVID-19 Pandemic and Pathways Forward.

PURPOSE: The purpose of this study was to explore how teleaudiology is perceived by Australian-based hearing health care stakeholders (clients, clinicians, students, academics, and industry partners) to inform future teleaudiology implementation. METHOD: Five cross-sectional online surveys were adopted, and a total of 366 stakeholders responded (173 clients, 110 clinicians, 58 students, 19 academics, and six industry partners). RESULTS: Results show that 55% of clients and over 90% of clinicians, students, academics, and industry partners knew what teleaudiology was. Experience in teleaudiology appointments was shared by 85% of clinicians and 7% of clients. Moreover, 98% of clients were not offered any teleaudiology appointments. Teleaudiology apps were used by 66% of clinicians and 26% of clients. Both clients and clinicians acknowledged the benefits of teleaudiology including convenience and accessibility and identified drawbacks, such as loss of personal interaction and communication difficulty. About 80% of students and academics reported inclusion of teleaudiology within their universities' curriculum but only to a limited extent. Low teleaudiology uptake rates in placement clinics, as well as insufficient funding and staffing, were suggested as barriers to learning and teaching teleaudiology. Industry partners were generally confident in training clinicians to use teleaudiology products and teaching students on teleaudiology, but only one industry partner had been invited by universities for teaching purposes. CONCLUSIONS: Low teleaudiology use and reserved attitudes toward widespread teleaudiology implementation were observed among clients. Clinicians, students, academics, and industry partners generally displayed positive attitudes toward teleaudiology use. Increasing awareness of teleaudiology services and collaboration between stakeholders are crucial in promoting teleaudiology uptake. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23519292.

Patient-reported outcomes in immunotherapy for head and neck cancer.

BACKGROUND: Data about patient-reported outcomes (PROs) among patients with head and neck squamous cell carcinoma (HNSCC) treated with immune checkpoint inhibitors are sparse. Our exploratory study evaluated PROs in patients with HNSCC starting treatment with immune checkpoint inhibitor monotherapy or combination therapy with cetuximab. METHODS: Patients were recruited prior to receipt of their first checkpoint inhibitor therapy infusion. Participants completed measures of checkpoint inhibitor toxicities and quality of life (QOL) at on-treatment clinic visits. RESULTS: Among patients treated with checkpoint inhibitor monotherapy (n = 48) or combination therapy (n = 38) toxicity increased over time (p < 0.05), while overall QOL improved from baseline to 12 weeks, with stable or declining QOL thereafter (p < 0.05). There were no group differences in change in toxicity index or QOL. Toxicity index scores were significantly higher in the combination group at 18-20 weeks and 6 months post-initiation of immune checkpoint inhibitor (p < 0.05). There were no significant group differences at baseline, the 6-8 week (p = 0.13) or 3-month (p = 0.09) evaluations. The combination group reported better emotional well-being at baseline than the monotherapy group (p = 0.04), There were no other group differences QOL at baseline or later timepoints. CONCLUSIONS: Despite increasing patient-reported toxicity, checkpoint inhibitor monotherapy and combination therapy were associated with similar transient improvements, then worsening, of QOL in patients with HNSCC.

Phase 1 Dose Escalation of Stereotactic Body Radiation Therapy and Concurrent Cisplatin for Reirradiation of Unresectable, Recurrent Squamous Cell Carcinoma of the Head and Neck.

PURPOSE: Patients with locoregional recurrence of squamous cell carcinoma of the head and neck (SCCHN) have relatively poor outcomes; therefore, stereotactic body radiation therapy (SBRT) has been investigated for this patient population. We performed a phase 1 clinical trial to establish a maximum tolerated dose of SBRT with concurrent cisplatin in previously irradiated locoregional SCCHN. METHODS AND MATERIALS: Patients with recurrent SCCHN who had previously undergone radiation therapy to doses ≥45 Gy to the area of recurrence ≥6 months before enrollment and who were not surgical candidates or refused surgery were eligible. SBRT was delivered every other day for 5 fractions. Starting dose level was 6 Gy × 5 fractions, followed by 7 Gy × 5 fractions and 8 Gy × 5 fractions. Chemotherapy consisted of cisplatin given before every SBRT fraction at a dose of 15 mg/m2. Patients were monitored for dose-limiting toxicities (DLT) that occurred within 3 months from the start of SBRT. Secondary endpoints included locoregional failure, distant metastasis, and overall survival. RESULTS: Twenty patients were enrolled, with 18 patients evaluable for endpoints. One patient at dose level 1 (30 Gy) died of unknown causes 2 weeks following completion of treatment. Therefore, an additional 3 patients were accrued to the 30-Gy dose level, with no further DLTs observed. Three patients were then accrued at dose level 2 (35 Gy) and 9 patients at dose level 3 (40 Gy) without DLTs. At a median follow-up of 9.5 months, cumulative incidence of locoregional failure at 2 years was 61% (95% confidence interval [CI], 12%-66%), cumulative incidence of distant metastasis was 11% (95% CI, 74%-100%) at 2 years, and overall survival was 22% (95% CI, 9%-53%) at 2 years. CONCLUSIONS: Concurrent cisplatin and reirradiation with an SBRT dose of ≤40 Gy was safe and feasible in patients with locoregionally recurrent or second primary SCCHN.

A systematic review on the efficacy of tranexamic acid in head and neck surgery.

BACKGROUND: Intraoperative and postoperative blood loss is a major risk in head and neck (H&N) surgery. Recently the use of tranexamic acid (TXA) has been investigated by multiple studies for reducing intraoperative and postoperative bleeding, however reported results are variable. OBJECTIVES: To determine the safety and efficacy of TXA use in H&N surgery. METHODS: Systematic review of MEDLINE, EMBASE, CINAHL, Cochrane Library, PubMed, ClinicalKey, and Clinicaltrials.gov according to the PRISMA guidelines. Studies were included if they reported on intraoperative bleeding, volume or duration of postoperative drain or return to theatre rate for postoperative haemorrhage in adult populations following use of TXA. Risk of bias assessment with Cochrane Risk of Bias (RoB2) tool for randomised controlled trials and Newcastle-Ottawa Scale tool for non-randomised studies. RESULTS: Sixteen studies were identified (114 407 patients). Eight studies evaluated TXA in major H&N surgery and eight studies in tonsillectomy. Primary outcomes were reduction in intraoperative or postoperative bleeding. Secondary outcomes included the duration of postoperative drain placement and return to theatre rate. No adverse events were reported in any patients. TXA is effective in reducing intraoperative blood loss in tonsillectomy. However, the effect on posttonsillectomy haemorrhage was unclear. Insufficient evidence exists of benefit of TXA on intraoperative bleeding in major H&N procedures. Postoperative drainage volumes were significantly reduced in most major H&N studies. The duration of drain placement and risk of blood transfusion was unchanged in most cases. CONCLUSION: TXA use is safe in H&N patients. Whilst sufficient evidence exists to support the use of TXA in tonsillectomy, insufficient evidence exists to recommend use in major H&N surgery.

Pembrolizumab and cabozantinib in recurrent metastatic head and neck squamous cell carcinoma: a phase 2 trial.

Anti-programmed cell death protein 1 (PD-1) therapy is a standard of care in recurrent metastatic head and neck squamous cell carcinoma (RMHNSCC). Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors, have immunomodulatory properties and have offered promising results when combined with anti-PD-1 agents. We conducted a phase 2, multicenter, single-arm trial of pembrolizumab and cabozantinib in patients with RMHNSCC who had Response Evaluation Criteria in Solid Tumors v.1.1 measurable disease and no contraindications to either agent. We assessed the primary end points of tolerability and overall response rate to the combination with secondary end points of progression-free survival and overall survival and performed correlative studies with PDL-1 and combined positive score, CD8+ T cell infiltration and tumor mutational burden. A total of 50 patients were screened and 36 were enrolled with 33 evaluable for response. The primary end point was met, with 17 out of 33 patients having a partial response (52%) and 13 (39%) stable disease with an overall clinical benefit rate of 91%. Median and 1-year overall survival were 22.3 months (95% confidence interval (CI) = 11.7-32.9) and 68.4% (95% CI = 45.1%-83.5%), respectively. Median and 1-year progression-free survival were 14.6 months (95% CI = 8.2-19.6) and 54% (95% CI = 31.5%-72%), respectively. Grade 3 or higher treatment-related adverse events included increased aspartate aminotransferase (n = 2, 5.6%). In 16 patients (44.4%), the dose of cabozantinib was reduced to 20 mg daily. The overall response rate correlated positively with baseline CD8+ T cell infiltration. There was no observed correlation between tumor mutational burden and clinical outcome. Pembrolizumab and cabozantinib were well tolerated and showed promising clinical activity in patients with RMHNSCC. Further investigation of similar combinations are needed in RMHNSCC. The trial is registered at ClinicalTrials.gov under registration no. NCT03468218 .

The Risk of Meningitis After Cochlear Implantation: A Systematic Review and Meta-Analysis.

OBJECTIVE: This study aims to estimate the rate of postoperative meningitis (both immediate and long-term) in patients following cochlear implants (CIs). It aims to do so through a systematic review and meta-analysis of published studies tracking complications after CIs. DATA SOURCES: MEDLINE, Embase, and Cochrane Library. REVIEW METHODS: This review was performed in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies tracking complications following CIs in patients were included. Exclusion criteria included non-English language studies and case series reporting <10 patients. Bias risk was evaluated using the Newcastle-Ottawa Scale. Meta-analysis was performed through DerSimonian and Laird random-effects models. RESULTS: A total of 116/1931 studies met the inclusion criteria and were included in the meta-analysis. Overall, there were 112 cases of meningitis in 58,940 patients after CIs. Meta-analysis estimated an overall rate of postoperative meningitis of 0.07% (95% confidence interval [CIs], 0.03%-0.1%; I2 = 55%). Subgroup meta-analysis showed this rate had 95% CIs crossing 0% in implanted patients who received the pneumococcal vaccine, antibiotic prophylaxis, those with postoperative acute otitis media (AOM), and those implanted less than 5 years. CONCLUSION: Meningitis is a rare complication following CIs. Our estimated rates of meningitis after CIs appear lower than prior estimates based on epidemiological studies in the early 2000s. However, the rate still appears higher than the baseline rate in the general population. The risk was very low in implanted patients who received the pneumococcal vaccine, antibiotic prophylaxis, received unilateral or bilateral implantations, developed AOM, those implanted with a round window or cochleostomy techniques, and those under 5 years.

Randomized Phase II Trial of Ficlatuzumab With or Without Cetuximab in Pan-Refractory, Recurrent/Metastatic Head and Neck Cancer.

PURPOSE: Primary or acquired resistance to cetuximab, an antiepidermal growth factor receptor monoclonal antibody (mAb), minimizes its utility in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Aberrant hepatocyte growth factor/cMet pathway activation is an established resistance mechanism. Dual pathway targeting may overcome resistance. PATIENTS AND METHODS: This multicenter, randomized, noncomparative phase II study evaluated ficlatuzumab, an antihepatocyte growth factor mAb, with or without cetuximab in recurrent/metastatic HNSCC. The primary end point was median progression-free survival (PFS); an arm met significance criteria if the lower bound of the 90% CI excluded the historical control of 2 months. Key eligibility criteria were HNSCC with known human papillomavirus (HPV) status, cetuximab resistance (progression within 6 months of exposure in the definitive or recurrent/metastatic setting), and resistance to platinum and anti-PD-1 mAb. Secondary end points included objective response rate (ORR), toxicity, and the association of HPV status and cMet overexpression with efficacy. Continuous Bayesian futility monitoring was used. RESULTS: From 2018 to 2020, 60 patients were randomly assigned and 58 were treated. Twenty-seven versus 33 patients were allocated to monotherapy versus combination. Arms were balanced for major prognostic factors. The monotherapy arm closed early for futility. The combination arm met prespecified significance criteria with a median PFS of 3.7 months (lower bound 90% CI, 2.3 months; P = .04); the ORR was 6 of 32 (19%), including two complete and four partial responses. Exploratory analyses were limited to the combination arm: the median PFS was 2.3 versus 4.1 months (P = .03) and the ORR was 0 of 16 (0%) versus 6 of 16 (38%; P = .02) in the HPV-positive versus HPV-negative subgroups, respectively. cMet overexpression was associated with reduced hazard of progression in HPV-negative but not HPV-positive disease (P interaction = .02). CONCLUSION: The ficlatuzumab-cetuximab arm met significance criteria for PFS and warrants phase III development. HPV-negative HNSCC merits consideration as a selection criterion.

Management and outcomes of military penetrating neck injuries: An eleven-year retrospective case note review.

INTRODUCTION: Penetrating Neck Injuries (PNIs) affected 3.2% of trauma patients attending US and UK deployed medical treatment facilities (MTFs) during the Iraq and Afghanistan conflicts. Injured military personnel requiring aeromedical evacuation for such injuries were managed at the Royal Centre for Defence Medicine (RCDM), Birmingham, UK. The aim of this paper was to review the management of PNI in both deployed MTFs and when evacuated back to the UK. PATIENTS AND METHODS: A retrospective case note review was performed of all military patients who sustained PNI whilst on deployment overseas, and who were subsequently evacuated to RCDM between March 2003 and December 2014. RESULTS: Forty casualties who sustained PNI were identified, of which 28/40 (70%) sustained injury from explosive fragmentation, and 11/40 (28%) from gunshot wounds. Hard signs of PNI were present in 3/40 (7.5%) patients, soft signs in 14/40 (35%), no signs in 12/40 (30%), and unknown signs in 11/40 (28%) patients. Computed tomography angiography (CTA) was used in 39/40 (98%) patients, and was effective at ruling out significant injury, with 100% (29/29) of casualties with a negative CTA not developing vascular or aerodigestive injury. There were 9/29 (31%) patients who had surgical neck exploration despite both a negative CTA and absence of hard signs of PNI. There were 12/40 (30%) patients who required operative intervention at RCDM. CONCLUSION: UK military surgeons in Role 3 MTFs had a low threshold for surgical exploration, even in the absence of CT findings or hard signs. This was likely due to the high-energy mechanisms responsible for military PNI, in addition to the limited availability of equipment and clinical expertise in visualising the larynx.