Anatomical determinants of occipitocervical fusion in skull base chordoma resection: a systematic review of the literature with illustrative cases.

OBJECTIVE: Skull base chordomas are rare, locally osseo-destructive lesions that present unique surgical challenges due to their involvement of critical neurovascular and bony structures at the craniovertebral junction (CVJ). Radical cytoreductive surgery improves survival but also carries significant morbidity, including the potential for occipitocervical (OC) destabilization requiring instrumented fusion. The published experience on OC fusion after CVJ chordoma resection is limited, and the anatomical predictors of OC instability in this context remain unclear. METHODS: PubMed and Embase were systematically searched according to the PRISMA guidelines for studies describing skull base chordoma resection and OC fusion. The search strategy was predefined in the authors' PROSPERO protocol (CRD42024496158). RESULTS: The systematic review identified 11 surgical case series describing 209 skull base chordoma patients and 116 (55.5%) who underwent OC instrumented fusion. Most patients underwent lateral approaches (n = 82) for chordoma resection, followed by midline (n = 48) and combined (n = 6) approaches. OC fusion was most often performed as a second-stage procedure (n = 53), followed by single-stage resection and fusion (n = 38). The degree of occipital condyle resection associated with OC fusion was described in 9 studies: total unilateral condylectomy reliably predicted OC fusion regardless of surgical approach. After lateral transcranial approaches, 4 studies cited at least 50%-70% unilateral condylectomy as necessitating OC fusion. After midline approaches-most frequently the endoscopic endonasal approach (EEA)-at least 75% unilateral condylectomy (or 50% bilateral condylectomy) led to OC fusion. Additionally, resection of the medial atlantoaxial joint elements (the C1 anterior arch and tip of the dens), usually via EEA, reliably necessitated OC fusion. Two illustrative cases are subsequently presented, further exemplifying how the extent of CVJ bony elements removed via EEA to achieve complete chordoma resection predicts the need for OC fusion. CONCLUSIONS: Unilateral total condylectomy, 50% bilateral condylectomy, and resection of the medial atlantoaxial joint elements were the most frequently described independent predictors of OC fusion in skull base chordoma resection. Additionally, consistent with the occipital condyle harboring a significantly thicker joint capsule at its posterolateral aspect, an anterior midline approach seems to tolerate a greater degree of condylar resection (75%) than a lateral transcranial approach (50%-70%) prior to generating OC instability.

Extreme lateral infracondylar approach for internal jugular vein compression syndrome: A case series with preliminary clinical outcomes.

BACKGROUND AND OBJECTIVES: Internal jugular vein (IJV) stenosis is associated with several neurological disorders including idiopathic intracranial hypertension (IIH) and pulsatile tinnitus. In cases of extreme bony compression causing stenosis in the infracondylar region, surgical decompression might be necessary. We aim to examine the safety and efficacy of surgical IJV decompression. METHODS: We retrospectively reviewed patients who received surgical IJV decompression via the extreme lateral infracondylar (ELI) approach between July 2020 and February 2022. RESULTS: Fourteen patients with IJV stenosis were identified, all with persistent headache and/or tinnitus. Six patients were diagnosed with IIH, three of whom failed previous treatment. Of the eight remaining patients, two failed previous treatment. All underwent surgical IJV decompression via styloidectomy, release of soft tissue, and removal of the C1 transverse process (TP). Follow-up imaging showed significant improvement of IJV stenosis in eleven patients and mild improvement in three. Eight patients had significant improvement in their presenting symptoms, and three had partial improvement. Two patients received IJV stenting after a lack of initial improvement. Two patients experienced cranial nerve paresis, and one developed a superficial wound infection. CONCLUSION: The ELI approach for IJV decompression appears to be safe for patients who are not ideal endovascular candidates due to bony anatomy. Confirming long-term efficacy in relieving debilitating clinical symptoms requires longer follow-up and a larger patient cohort. Carefully selected patients with symptomatic bony IJV compression for whom there are no effective medical or endovascular options may benefit from surgical IJV decompression.

Cranial transposition and revascularization of autologous omentum: a novel surgical technique for resection of recurrent glioblastoma multiforme.

Glioblastoma multiforme (GBM) patients continue to suffer a poor prognosis. The blood brain barrier (BBB) comprises one of the obstacles for therapy, creating a barrier that decreases the bioavailability of chemotherapeutic agents in the central nervous system. Previously, a vascularized temporoparietal fascial scalp flap (TPFF) lining the resection cavity was introduced in a trial conducted in our institution, in newly-diagnosed GBM patients in an attempt to bypass the BBB after initial resection. In this paper, we report on a new technique to bypass the BBB after re-resection and potentially to allow tumor antigens to be surveilled by the immune system. The study aims to assess the feasibility of performing a cranial transposition and revascularization of autologous omentum after re-resection of GBM. Laparoscopically harvested omental free flap was transposed to the resection cavity by a team consisting of neurosurgeons, otolaryngologists, and general surgeons. This was done as part of a single center, single arm, open-label, phase I study. Autologous abdominal omental tissue was harvested laparoscopically on its vascularized pedicle in 2 patients, transposed as a free flap, revascularized using external carotid artery, and carefully laid into the tumor resection cavity. Patients did well postoperatively returning to baseline activities. Graft viability was confirmed by cerebral angiogram. Omental cranial transposition of a laparoscopically harvested, vascularized flap, into the cavity of re-resected GBM patients is feasible and safe in the short term. Further studies are needed to ascertain whether such technique can improve progression free survival and overall survival in these patients.

Viral markers in nasopharyngeal carcinoma: A systematic review and meta-analysis on the detection of p16INK4a, human papillomavirus (HPV), and Ebstein-Barr virus (EBV).

PURPOSE: This study aimed to conduct a meta-analysis to investigate the distribution of EBV and HPV stratified according to histological NPC type. MATERIALS & METHODS: We performed a meta-analysis to produce pooled prevalence estimates in a random-effects model. We also performed calculations for attributable fractions of viral combinations in NPC, stratified according to histological type. RESULTS: There was a higher prevalence of HPV DNA in WHO Type I (34.4%) versus WHO Type II/III (18.4%). The attributable fractions of WHO Type I NPC was predominantly double negative EBV(-) HPV(-) NPC (56.4%), and EBV(-) HPV(+) NPC (21.5%), in contrast to the predominant infection in WHO Type II/III which was EBV(+) HPV(-) NPC (87.5%). Co-infection of both EBV and HPV was uncommon, and double-negative infection was more common in WHO Type I NPC. CONCLUSION: A significant proportion of WHO Type I NPC was either double-negative EBV(-)HPV(-) or EBV(-)HPV(+).

The Prognostic Role of Programmed Death-Ligand 1 in Nasopharyngeal Carcinoma.

OBJECTIVES: Programmed death-ligand 1 (PD-L1) is an immune checkpoint protein that may be a useful prognostic biomarker in nasopharyngeal cancer (NPC). The purpose of this systematic review and meta-analysis was to investigate the relationship between PD-L1 expression and survival in NPC. METHODS: PubMed, Cochrane, Embase, Scopus, and Web of Science were searched from inception to present. A predefined inclusion and exclusion criteria were used to select articles. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled for overall survival (OS), disease-free survival (DFS), and disease metastasis-free survival (DMFS). RESULTS: Eleven studies published from 2014 to 2018 were included, with 1,356 total participants. PD-L1 expression was not associated with OS (HR = 1.10, 95% CI: 0.79-1.55), DFS (HR = 1.66, 95% CI: 0.68-4.03), or DMFS (HR = 1.18, 95% CI: 0.44-3.20). CONCLUSIONS: The prognostic role of PD-L1 in NPC remains unsubstantiated. Future research is needed. Laryngoscope, 130:2598-2606, 2020.

Internal Maxillary to Middle Cerebral Artery Bypass Using an Anterior Tibial Artery Graft, Performed Using a 3-Dimensional Exoscope: 2-Dimensional Operative Video.

Fusiform aneurysms remain challenging entities to treat, as maintenance of flow and prevention of branch occlusion are concerns. Use of endovascular stents may risk nearby branch occlusion. We present a 31-yr-old male with a prior subarachnoid hemorrhage from a left middle cerebral artery (MCA) M1 aneurysm. Informed consent for use of the operative video and information was obtained from the patient. Initially, open clipping was performed with noted residual because of risk of nearby branches. On angiography, a growing fusiform segment distal to the initial aneurysm was noted. The patient was referred to our institution for this finding, and a multidisciplinary team reviewed the case. Endovascular treatment was felt to be risky, as stenting could jail nearby MCA branches. Clipping would also risk occlusion because of scaring from previous hemorrhage. Sufficient flow would be needed, and because the ipsilateral superficial temporal artery was sacrificed in the initial craniotomy, the internal maxillary artery (IMAX) was chosen as the bypass source. A cerebrovascular neurosurgeon, skull base otolaryngologist, and vascular surgeon worked together to perform a left-side IMAX to MCA bypass using an anterior tibial artery graft under 3-dimensional exoscopic visualization. Specifically, a 9-0 nylon suture on a BV-130 needle along with straight and tying forceps were used along with heparinized saline. The bypass was noted to be of robust flow, and the patient did very well on postoperative follow-up. The utilization of an anterior tibial artery graft, IMAX exposure, and corresponding bypass provides educational value, as there are only a limited number of videos on this topic.

Anatomical subsite modifies survival in oropharyngeal squamous cell carcinoma: National Cancer Database study.

BACKGROUND: Oropharyngeal squamous cell carcinomas (OPSCC) can occur in either tonsillar related areas (TRA) or nontonsillar areas (nTRA). The prognostic differences between these sites are unclear. This study investigated this question using the National Cancer Database (NCDB), controlling for other confounders including human papillomavirus (HPV) status. METHODS: This NCDB study was conducted by stratifying the HPV-positive oropharyngeal cancer cohort into two primary groups, TRA and nTRA. Kaplan Meier survival analysis was stratified according to HPV status, and further analysis was conducted using multivariable Cox regression. RESULTS: A total of 23 297 patients were included in this study. In the multivariable cox regression analysis, OPSCC subsite was found to be an independent prognostic factor for survival (TRA vs nTRA HR: 0.76, 95% CI: 0.67-0.86, P < .0001). CONCLUSION: In this large cohort, OPSCC subsite was found to be an independent prognostic factor for survival.

Safety and efficacy of sphenopalatine ganglion stimulation for chronic cluster headache: a double-blind, randomised controlled trial.

BACKGROUND: Chronic cluster headache is the most disabling form of cluster headache. The mainstay of treatment is attack prevention, but the available management options have little efficacy and are associated with substantial side-effects. In this study, we aimed to assess the safety and efficacy of sphenopalatine ganglion stimulation for treatment of chronic cluster headache. METHODS: We did a randomised, sham-controlled, parallel group, double-blind, safety and efficacy study at 21 headache centres in the USA. We recruited patients aged 22 years or older with chronic cluster headache, who reported a minimum of four cluster headache attacks per week that were unsuccessfully controlled by preventive treatments. Participants were randomly assigned (1:1) via an online adaptive randomisation procedure to either stimulation of the sphenopalatine ganglion or a sham control that delivered a cutaneous electrical stimulation. Patients and the clinical evaluator and surgeon were masked to group assignment. The primary efficacy endpoint, which was analysed with weighted generalised estimated equation logistic regression models, was the difference between groups in the proportion of stimulation-treated ipsilateral cluster attacks for which relief from pain was achieved 15 min after the start of stimulation without the use of acute drugs before that timepoint. Efficacy analyses were done in all patients who were implanted with a device and provided data for at least one treated attack during the 4-week experimental phase. Safety was assessed in all patients undergoing an implantation procedure up to the end of the open-label phase of the study, which followed the experimental phase. This trial is registered with ClinicalTrials.gov, number NCT02168764. FINDINGS: Between July 9, 2014, and Feb 14, 2017, 93 patients were enrolled and randomly assigned, 45 to the sphenopalatine ganglion stimulation group and 48 to the control group. 36 patients in the sphenopalatine ganglion stimulation group and 40 in the control group had at least one attack during the experimental phase and were included in efficacy analyses. The proportion of attacks for which pain relief was experienced at 15 min was 62·46% (95% CI 49·15-74·12) in the sphenopalatine ganglion stimulation group versus 38·87% (28·60-50·25) in the control group (odds ratio 2·62 [95% CI 1·28-5·34]; p=0·008). Nine serious adverse events were reported by the end of the open-label phase. Three of these serious adverse events were related to the implantation procedure (aspiration during intubation, nausea and vomiting, and venous injury or compromise). A fourth serious adverse event was an infection that was attributed to both the stimulation device and the implantation procedure. The other five serious adverse events were unrelated. There were no unanticipated serious adverse events. INTERPRETATION: Sphenopalatine ganglion stimulation seems efficacious and is well tolerated, and potentially offers an alternative approach to the treatment of chronic cluster headache. Further research is need to clarify its place in clinical practice. FUNDING: Autonomic Technologies.

Platelet-Lymphocyte Ratio as a Predictor of Prognosis in Head and Neck Cancer: A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis was to investigate the prognostic utility of the platelet-to-lymphocyte ratio (PLR) in head and neck cancer. Medline (via PubMed), EMBASE, Scopus, and the Cochrane Library databases were searched from their inception to May 2017 for relevant literature. A systematic review and meta-analysis were performed to generate the pooled hazard ratios (HR) for overall survival (OS) and disease-specific survival (DSS). The study was conducted in accordance with the Cochrane Handbook and PRISMA guidelines. Risk of bias was assessed using the QUIPS tool. The logarithm of the HR with standard error was used as the primary summary statistic. Heterogeneity was assessed using Cochran's Q and Higgins' I2. A total of 13 studies were included in the final analysis, combining data from 4,541 patients. The results demonstrated that an elevated PLR was significantly associated with poorer OS [HR 1.85, 95% CI 1.35-2.52, p < 0.00001] and DSS [HR 1.57, 95% CI 1.25-1.97, p < 0.0001]. Significant heterogeneity was detected for the pooled end points. Subgroup analysis demonstrated reduction of heterogeneity by controlling for sample size and cutoff value. 95% prediction intervals showed wide ranges crossing the null threshold.

Systemic immune response in squamous cell carcinoma of the head and neck: a comparative concordance index analysis.

PURPOSE: The objective of this study was to investigate the prognostic role of three inflammatory markers: the neutrophil to lymphocyte ratio (NLR), the lymphocyte to monocyte ratio (LMR), and the platelet to lymphocyte ratio (PLR) as prognostic indicators in squamous cell carcinoma of the head and neck (HNSCC). METHODS: Patients with HNSCC treated with primary surgery, with or without adjuvant radiochemotherapy were enrolled. The preoperative NLR, LMR, and PLR were recorded. Confounding variables were also recorded: age, sex, BMI, comorbidities, performance status, AJCC T and N stage and HPV status. Endpoints were overall survival (OS) and event-free survival (EFS). Survival analysis was performed using Kaplan-Meier analysis, and multivariable analysis was performed using Cox proportional hazards regression. Survival models were evaluated using Harrell's concordance index (c-index). RESULTS: NLR (p = 0.2413), PLR (p = 0.1593), and LMR (p = 0.0552) were not significantly associated with OS in the multivariable analysis. With regard to EFS, low LMR (HR = 2.95, 95% CI 1.54-5.65, p = 0.001), high PLR (HR = 2.68, 95% CI 1.42-5.09, p = 0.003), and high NLR (HR = 3.37, 95% CI 1.7-6.69, p < 0.001) were associated with EFS. The multivariable c-index was highest for LMR (0.762), followed by NLR (0.761) and PLR (0.739). CONCLUSION: The LMR, PLR, and NLR were not associated with OS, but were associated with EFS in HNSCC. These markers are easily obtainable, and in the age of individualized patient care and precision medicine, they might represent further risk stratification tools for HNSCC patients.

HPV status in patients with nasopharyngeal carcinoma in the United States: A SEER database study.

PURPOSE: To investigate the etiologic and prognostic role of Human Papilloma Virus (HPV) in Nasopharyngeal Carcinoma (NPC). MATERIALS AND METHODS: Patients diagnosed with NPC were identified with the Surveillance, Epidemiology, and End Results (SEER) database. Logistic regression was used to investigate the effect of clinicopathologic predictors on HPV positivity in NPC. Survival analyses were performed with Kaplan-Meier curves and Cox regression models. RESULTS: 180/517 patients (34.8%) with known HPV testing were positive for HPV-associated NPC. East Asians and individuals over 25 were less likely to have HPV-associated NPC, while controlling for AJCC-7 stage and AJCC-7 M stage. According to the survival analysis, cause-specific survival (CSS) did not differ significantly by HPV status throughout the study period, but did differ significantly by HPV ethnicity group. CONCLUSIONS: The clinical implications of HPV in NPC are further elucidated but require more investigation. LEVEL OF EVIDENCE: IV.

Evaluation of Time to Surgery and Its Effect on Prognosis in Head and Neck Cancer.

BACKGROUND: Recently, time to treatment initiation has been observed to be increasing specifically for head and neck cancer. It is acknowledged that the pattern of increase is reflective of the use of sophisticated diagnostic and therapeutic techniques but was also determined to affect survival. OBJECTIVES: Our study sought to further investigate time to surgery (TTS) for surgically treated patients to see whether TTS would influence patient survival. METHOD: TTS was defined as the time from the earliest pathological report or scan, whichever was earlier, to surgery. The endpoints were overall survival (OS) and event-free survival (EFS). RESULTS: A total of 294 patients with head and neck cancer were included. Patients were organized into TTS quartiles of 0-14 days (quartile 1), 15-29 days (quartile 2), 30-49 days (quartile 3), and ≥50 days (quartile 4). The median follow-up time was 651 days, and the median TTS was 32 days. Using a univariable analysis of Cox regression, TTS was not significantly associated with OS or EFS. Kaplan-Meier curves were not significant for OS (p = 0.8904) and EFS (p = 0.9556). CONCLUSION: In this cohort study, we could not conclude that TTS was associated with OS or EFS.

The prognostic effect of anatomic subsite in HPV-positive oropharyngeal squamous cell carcinoma.

BACKGROUND: Since most HPV-associated disease occurs in the tonsillar-related areas (TRA) - palatine and lingual tonsils, the effect of HPV on survival in non-tonsillar oropharyngeal subsites (nTRA) is not well established. The objective of this study was to use a large population-based cohort to investigate the survival impact of HPV in nTRA subsites versus TRA subsites. METHODS: This SEER database study was conducted by stratifying the HPV-positive oropharyngeal cancer cohort into two primary groups, TRA and nTRA. RESULTS: HPV-positive squamous cell cancer was significantly more common in TRAs (73%) compared to nTRAs (31.2%, p < 0.001). After controlling for age, treatment, stage, race, and income, patients with HPV-positive disease in nTRAs had a worse cause-specific survival (CSS) than individuals with HPV-positive disease in TRAs (HR = 2.16, 95% CI 1.20-3.86, p = 0.01). CONCLUSION: Patients with HPV-positive OPSCC in nTRAs had poorer survival outcomes compared to patients with HPV-positive OPSCC in TRAs.

Evaluation of the prognostic utility of the combination of platelet count with mean platelet volume as a prognostic indicator in head and neck cancer.

The combination of platelet count to mean platelet volume (COP-MPV) has been recently reported as a prognostic indicator of oral cavity cancer and other cancer sites. The aim of the present study was to validate the utility of the COP-MPV as a prognostic indicator in all head and neck cancer (HNC) sites. The clinicopathological characteristics of the COP-MPV with HNC were also investigated. This is a retrospective cohort study that recruited consecutively treated patients at a tertiary level academic hospital. Clinicopathological characteristics were recorded, including the COP-MPV scores. Survival was analyzed using Kaplan-Meier analysis, as well as multivariate Cox Proportional Hazards regression. COP-MPV was not associated with the survival outcome in univariate or multivariate analysis. In the multivariate model, tumor differentiation, tumor stage, nodal stage, surgical margins and hemoglobin were revealed to be significantly associated with survival. The results demonstrated that the COP-MPV is not a suitable prognostic factor for HNC.

Personalized prognostication in head and neck cancer: A systematic review of nomograms according to the AJCC precision medicine core (PMC) criteria.

BACKGROUND: The American Joint Committee on Cancer (AJCC) Precision Medicine Core (PMC) has recognized the need for more personalized probabilistic predictions above the "TNM" staging system and has recently released a checklist of inclusion and exclusion criteria for evaluating prognostic models. METHODS: A systematic review of articles in which nomograms were created for head and neck cancer (HNC) was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The AJCC PMC criteria were used to score the individual studies. RESULTS: Forty-four studies were included in the final qualitative analysis. The mean number of inclusion criteria met was 9.3 out of 13, and the mean number of exclusion criteria met was 2.1 out of 3. Studies were generally of high quality, but no single study fulfilled all of the AJCC PMC criteria. CONCLUSION: This is the first study to utilize the AJCC checklist to comprehensively evaluate the published prognostic nomograms in HNC. Future studies should attempt to adhere to the AJCC PMC criteria. Recommendations for future research are given. SUMMARY: The AJCC recently released a set of criteria to grade the quality of prognostic cancer models. In this study, we grade all published nomograms for head and neck cancer according to the new guidelines.

Anaphylactoid hypersensitivity reaction from intra-arterial cetuximab: Clinical considerations and management.

Intra-arterial infusion of drugs shows promising results in terms of safety and efficacy. Intra-arterial cetuximab, a monoclonal antibody treatment, is currently being tested for its use in head and neck cancers. We present the case of a 45-year-old Asian male who developed an anaphylactoid hypersensitivity reaction, manifesting itself in the form of bronchospasm, tachycardia, and hypotension, during intra-arterial infusion of cetuximab. The symptoms were quickly diagnosed, and the patient was treated accordingly. Despite the safety profile of cetuximab and the decreased risk of systemic effects with intra-arterial infusion versus intravenous infusion, severe hypersensitivity reactions are still a risk in intra-arterial cetuximab infusions. Consequently, proper planning and care must be taken to prophylactically prevent and in the case of a reaction, treat the reaction accordingly. The case presented herein is, to the best of our knowledge, the first recorded moderate-to-severe infusion reaction in a patient receiving intra-arterial cetuximab treatment for head and neck cancer.

Survival impact of treatment-related time intervals in nasopharyngeal carcinoma in the United States.

OBJECTIVE: To determine if delayed or prolonged treatment-related time intervals (TRTIs) was associated with survival in patients with nasopharyngeal carcinoma (NPC) undergoing curative-intent concurrent chemoradiation (CCRT). The TRTIs investigated were duration of radiation treatment (RTd), time to radiation start (TTR), and time to chemotherapy start (TTC). METHODS: Observational cohort study using the National Cancer Database (NCDB). In this observational cohort study, 3,893 eligible patients with NPC were identified from the NCDB. Patients received CCRT of at least 66 grays and radiation treatment time of at least 40 days. Separate univariable Cox regression model was used to analyze overall survival (OS) as a function of TRTIs, as well as for Charlson/Deyo Score, tumor classification, node classification, histological type, ethnicity, age, sex, and facility type. Upon finding significance at P < 0.05, the multivariable Cox regression analysis with backward elimination was performed to yield the final prediction model. Results were considered statistically significant when P < 0.05. RESULTS: Radiation treatment was significantly associated with OS in the univariable analysis (hazard ratio: 1.006, 95% confidence interval = 1.004-1.008, P < 0.001). However, RTd was not related to OS in the multivariable analysis (P = 0.19). The TTR and TTC variables were not associated with OS in the univariable analysis (P = 0.88 and P = 0.88, respectively). CONCLUSION: TRTIs were not independently associated with OS in this cohort of NPC patients in the NCDB. Future research into the association of TRTI with other disease outcomes, such as disease-free survival and locoregional control, is needed. LEVEL OF EVIDENCE: NA. Laryngoscope, 129:2514-2520, 2019.

Comparison of venous thromboembolism risk stratification models in a high risk otolaryngology patient cohort.

Our objective was to compare the venous thromboembolism outcomes in two of the most commonly utilised venous thromboembolism assessment tools, the Caprini system and the University of Michigan system, in a high risk head and neck surgery population. Currently, there is a lack of data reporting the validation of well known scoring systems in this patient population. Established risk factors for venous thromboembolism were included in the data collection process. We retrospectively evaluated all patients with the Caprini Risk Assessment and the University of Michigan Health System (UMHS) Scores. Out of all the risk factors, only length of surgery was found to be associated with venous thromboembolism. The mean Caprini scores in those with and without venous thromboembolism were 8.00 ± 3.00 and 6.86 ± 1.45, respectively. The mean UMHS scores in those with and without venous thromboembolism were 6.85 ± 1.28 and 6.54 ± 1.20, respectively. Both scoring systems were not found to be associated with venous thromboembolism.

Efficacy of a non-invasive middle ear aeration device in children with recurrent otitis media: A randomized controlled trial protocol.

Acute otitis media (AOM) represents a significant disease burden in the pediatric population. Besides vaccinations, there are no robust measures of reducing incidence of AOM in this age-group. This is a randomized controlled clinical trial evaluating the efficacy of a non-invasive middle ear aeration device, the EarPopper device (EP). We aim to investigate the reduction of episodes AOM in children with recurrent otitis media. The control arm will be observational. The intervention arm will have the EP used. The primary endpoint is incidence of AOM. The secondary endpoints are hazard ratio of time to AOM, proportion without AOM and antibiotics use, quality of life (OMO-22 Form), and adherence to treatment. Sample size is a minimum of 150 patients. The inclusion criteria is ages 4-11, with history of recurrent Acute Otitis Media (AOM).