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INTRODUCTION: Pathway innovation using smartphone otoscopy and tablet-based audiometry technologies to deliver ear and hearing services via trained audiologists may improve efficiency of the service. An ENT-integrated-community-ear service (ENTICES-combining community audiology management, remote ENT review and novel technologies) was piloted. We aimed to assess the efficiency and safety of ENTICES. METHOD: ENTICES was a community-based and audiologist-led pathway. Patients with otological symptoms were self-referred to this service. Smartphone otoscopy and tablet-based audiograms were performed. Two otologists reviewed all decisions made in the community by audiologists based on video-otoscopy, hearing tests and chart reviews. Data on the first 50 consecutive new patients attending either consultant-led hospital otology clinics (HOC), audiologist-led hospital advanced audiology diagnostics (AAD) or ENTICES clinics were collected between 1 August 2021 and 31 December 2021. Data were collected through chart reviews and questionnaires to compare the three pathways with respect to efficiency, patient satisfaction, technology utility and safety. RESULTS: No audiology-led ENTICES decisions were amended by hospital otologists following remote review. Remote review of video-otoscopy with history was sufficient for a diagnosis in 80% of cases. Adding hearing tests and standardised history increased the diagnostic yield to 98%. Patient satisfaction scores showed 100% service recommendation. The cost per patient, per visit, was £83.36, £99.07 and £69.72 for AAD, HOC or ENTICES, respectively. CONCLUSION: ENTICES provides a safe ear and hearing service that patients rated highly. Thirty-two per cent of hospital otology patients were eligible for this service. For those patients, ENTICES is 20% more cost-effective and can reduce the number of clinic visits by up to 60% compared with HOC.
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Otolaringología , Telemedicina , Humanos , Proyectos Piloto , Masculino , Femenino , Persona de Mediana Edad , Adulto , Otoscopía/métodos , Anciano , Enfermedades del Oído/diagnóstico , Enfermedades del Oído/terapia , Satisfacción del Paciente , Audiometría , Adolescente , Derivación y ConsultaRESUMEN
The current diagnostic criteria for traumatic brain injury (TBI) are heavily reliant on an accurate clinical history of events. Diagnosis of mild injury relies on one or more of the following: confusion or disorientation, loss of consciousness (LOC) for 30 min or less, post-ictus amnesia for less than 24 h and/or other transient neurological abnormalities and a Glasgow Coma Score (GCS). Given the nature of the condition it is obvious that significant clinical challenges remain to identify in the cases of mild TBI, and additionally to grade more severe forms so that appropriate treatment is received. The lack of clinically useful biomarkers in the serum of TBI patients is a significant barrier to improving their outlook. Discovery of such markers would aid the timely diagnosis of novel and recurrent disease in a minimally invasive manner. A PubMed search was performed to identify studies reporting serum biomarkers in traumatic brain injury. Details regarding the biomarkers analysed, specificity, indications for outcome and statistical significance were recorded. A total of 40 manuscripts reporting 11 biomarkers were identified in the literature. All but a few studies reported statistically significant differences in biomarker expression between groups. We conclude that serum biomarkers of TBI are an effective means for investigating the condition. However, the lack of novel markers identified in this mass of studies highlights the need to adopt new measure of biomarker identification.
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Biomarcadores/sangre , Lesiones Encefálicas/diagnóstico , Lesiones Encefálicas/sangre , Humanos , Valor Predictivo de las PruebasRESUMEN
Objectives Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past. Methods We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed. Results One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic ( p < 0.001) with implications for a potential modification to the current TNM staging system. There was a statistically significant survival benefit for patients who received adjuvant radiotherapy, compared with those who underwent surgery alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI]: 0.57-0.96, p = 0.021). Immune checkpoint blockade for the management of recurrent or persistent disease, with or without distant metastasis, conferred longer survival (HR = 0.50, 95% CI: 0.25-1.00, p = 0.036). Conclusions We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field.
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INTRODUCTION: The COVID-19 pandemic has catalysed the need to implement the National Health Service Long-Term Plan to deliver more care in the community and to reduce face-to-face hospital appointments by up to 33%. This study aimed to assess the feasibility of a remote otology service from triage through to delivery. METHODS: New adult otology referrals at a tertiary ear, nose and throat (ENT) hospital aged between 18 and 70 with hearing loss or tinnitus were included. Patients attended an audiology-led community clinic where they underwent a focused history, audiometric testing, and a smartphone-based application and otoscope (Tympa System) was used to capture still and video images of their eardrums. The information was reviewed by ENT clinicians using a remote review platform with a subset of patients subsequently undergoing an in-person review to measure concordance between the two assessments. RESULTS: 58 patients participated. 75% of patients had their pathways shortened by one hospital visit with 65% avoiding any hospital attendances. 24% required an additional face-to-face appointment due to incomplete views of the tympanic membrane or need for additional examinations. Electronic validation by a blinded consultant otologist demonstrated a diagnosis concordance of 95%, and concordance between remote-review and in-person consultations in the 12 patients who agreed to attend for an in-person review was 83.3%. 98% of patients were satisfied with the pathway. CONCLUSION: This pilot service is feasible, safe and non-inferior to the traditional outpatient model in the included patient group. There is potential for the development of a community audiology-led service or use for general practioner advice and guidance.
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COVID-19 , Otolaringología , Adolescente , Adulto , Anciano , Estudios de Factibilidad , Humanos , Persona de Mediana Edad , Pandemias , SARS-CoV-2 , Medicina Estatal , Reino Unido , Adulto JovenRESUMEN
OBJECTIVE: To perform a matched cohort study to assess whether patients with Meniere's Disease (MD) require more intensive auditory rehabilitation following cochlear implantation (CI) and identify factors that may affect outcomes in patients with MD. METHODS: A retrospective case review was performed. MD and control patients were matched for age, biological sex, implant manufacturer and electrode design. Outcomes measured were speech scores, number of visits to audiology department following switch-on, and post-operative active MD. RESULTS: Forty consecutive implanted MD patients were identified between May 1993 and May 2019. Patients with active MD following CI required significantly more visits to the audiology department compared to controls (P < 0.01) and patients who had inactive MD post-operatively (P < 0.01). However, in MD patients, active MD was less likely following CI (P = 0.03). In patients who continued to experience active MD post-operatively, further medical and surgical ablative intervention was required to control ongoing Meniere's attacks. CONCLUSION: We present the largest case series of performance outcomes in CI patients with MD. Although speech outcomes in MD patients are comparable to controls, patients with active MD pre-operatively are more likely to experience variation in CI performance requiring a prolonged period of auditory rehabilitation compared to inactive preoperative MD.
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Implantación Coclear , Implantes Cocleares , Enfermedad de Meniere , Estudios de Cohortes , Humanos , Enfermedad de Meniere/cirugía , Estudios RetrospectivosRESUMEN
INTRODUCTION: Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy. METHODS: We conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe. Clinicopathological characteristics and treatment approach were evaluated. SSTR2 expression, SSTR2-targeted imaging and the efficacy of peptide receptor radionuclide therapy [PRRT](177Lu-DOTATATE) were reported in a subset of our cohort (LUTHREE trial; NCT03454763). RESULTS: Dural infiltration at presentation was a significant predictor of overall survival (OS) and disease-free survival (DFS) in primary cases (n = 278). Kadish-Morita staging and Dulguerov T-stage both had limitations regarding their prognostic value. Multivariable survival analysis demonstrated improved outcomes with lower stage and receipt of adjuvant radiotherapy. Prophylactic neck irradiation significantly reduces the rate of nodal recurrence. 82.4% of the cohort were positive for SSTR2; treatment of three metastatic cases with SSTR2-targeted peptide-radionuclide receptor therapy (PRRT) in the LUTHREE trial was well-tolerated and resulted in stable disease (SD). CONCLUSIONS: This study presents pertinent clinical data from the largest dataset, to date, on ONB. We identify key prognostic markers and integrate these into an updated staging system, highlight the importance of adjuvant radiotherapy across all disease stages, the utility of prophylactic neck irradiation and the potential efficacy of targeting SSTR2 to manage disease.
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Estesioneuroblastoma Olfatorio , Neuroblastoma , Neoplasias Nasales , Estesioneuroblastoma Olfatorio/patología , Estesioneuroblastoma Olfatorio/terapia , Humanos , Cavidad Nasal/metabolismo , Cavidad Nasal/patología , Neuroblastoma/patología , Neoplasias Nasales/radioterapia , Tomografía de Emisión de Positrones , Radioisótopos , Cintigrafía , Receptores de Somatostatina/metabolismo , Estudios RetrospectivosRESUMEN
Nasopharyngeal cancer (NPC), endemic in Southeast Asia, lacks effective diagnostic and therapeutic strategies. Even in high-income countries the 5-year survival rate for stage IV NPC is less than 40%. Here we report high somatostatin receptor 2 (SSTR2) expression in multiple clinical cohorts comprising 402 primary, locally recurrent and metastatic NPCs. We show that SSTR2 expression is induced by the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) via the NF-κB pathway. Using cell-based and preclinical rodent models, we demonstrate the therapeutic potential of SSTR2 targeting using a cytotoxic drug conjugate, PEN-221, which is found to be superior to FDA-approved SSTR2-binding cytostatic agents. Furthermore, we reveal significant correlation of SSTR expression with increased rates of survival and report in vivo uptake of the SSTR2-binding 68Ga-DOTA-peptide radioconjugate in PET-CT scanning in a clinical trial of NPC patients (NCT03670342). These findings reveal a key role in EBV-associated NPC for SSTR2 in infection, imaging, targeted therapy and survival.
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Infecciones por Virus de Epstein-Barr , Regulación Neoplásica de la Expresión Génica , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recurrencia Local de Neoplasia , Receptores de Somatostatina , Proteínas de la Matriz Viral , Animales , Femenino , Humanos , Masculino , Ratones , Antineoplásicos/farmacología , Línea Celular Tumoral , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/mortalidad , Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/efectos de los fármacos , Herpesvirus Humano 4/crecimiento & desarrollo , Herpesvirus Humano 4/patogenicidad , Interacciones Huésped-Patógeno/genética , Metástasis Linfática , Ratones Desnudos , Terapia Molecular Dirigida , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/virología , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/virología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/virología , FN-kappa B/genética , FN-kappa B/metabolismo , Octreótido/farmacología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Receptores de Somatostatina/antagonistas & inhibidores , Receptores de Somatostatina/genética , Receptores de Somatostatina/metabolismo , Transducción de Señal , Análisis de Supervivencia , Proteínas de la Matriz Viral/antagonistas & inhibidores , Proteínas de la Matriz Viral/genética , Proteínas de la Matriz Viral/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Sudden onset sensorineural hearing loss (SSNHL) is frequently seen by otolaryngologists. The exact pathophysiology of the disease is still unknown, with the most likely causative factor being following a viral infection. Immediate steroids are the best treatment to improve prognosis. Despite a plethora of papers in the literature describing SSNHL, there are only a few reported cases of hearing loss following COVID-19, none of which have been reported in the UK. This paper presents the first UK case of SSNHL following COVID-19. Physical examination and imaging excluded any other cause of hearing loss. A literature review showed that four other cases have been previously described. Hearing loss can be a significant cause of morbidity and can easily be missed in the intensive care setting. Being aware and screening for SSNHL following COVID-19 enables an early course of steroids, which offers the best chance of recovering hearing.
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Betacoronavirus , Infecciones por Coronavirus/complicaciones , Pérdida Auditiva Súbita/complicaciones , Pérdida Auditiva Súbita/tratamiento farmacológico , Hemisuccinato de Metilprednisolona/uso terapéutico , Neumonía Viral/complicaciones , Prednisolona/uso terapéutico , Administración Oral , COVID-19 , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Pérdida Auditiva Súbita/diagnóstico , Humanos , Inyecciones , Masculino , Hemisuccinato de Metilprednisolona/administración & dosificación , Persona de Mediana Edad , Pandemias , Prednisolona/administración & dosificación , SARS-CoV-2RESUMEN
OBJECTIVES: p16INK4A (p16) is the most widely used clinical biomarker for Human Papillomavirus (HPV) in head and neck squamous cell cancer (HNSCC). HPV is a favourable prognostic marker in HNSCC and is used for patient stratification. While p16 is a relatively accurate marker for HPV within the oropharynx, recent reports suggest it may be unsuitable for use in other HNSCC subsites, where a smaller proportion of tumors are HPV-driven. MATERIALS AND METHODS: We integrated reverse phase protein array (RPPA) data for p16 with HPV status based on detection of viral transcripts by RNA-seq in a set of 210 HNSCCs profiled by The Cancer Genome Atlas project. Samples were queried for alterations in CDKN2A, and other pathway genes to investigate possible drivers of p16 expression. RESULTS: While p16 levels as measured by RPPA were significantly different by HPV status, there were multiple HPV (-) samples with similar expression levels of p16 to HPV (+) samples, particularly at non-oropharyngeal subsites. In many cases, p16 overexpression in HPV (-) tumors could not be explained by mutation or amplification of CDKN2A or by RB1 mutation. Instead, we observed enrichment for inactivating mutations in the histone H3 lysine 36 methyltransferase, NSD1 in HPV (-)/p16-high tumors. CONCLUSIONS: RPPA data suggest high p16 protein expression in many HPV (-) non-oropharyngeal HNSCCs, limiting its potential utility as an HPV biomarker outside of the oropharynx. HPV-independent overexpression of wild-type p16 in non-oropharyngeal HNSCC may be linked to global deregulation of chromatin state by inactivating mutations in NSD1.