Plasma cell-free DNA methylome profiling in pre- and post-surgery oral cavity squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC), a highly heterogeneous disease that involves multiple anatomic sites, is a leading cause of cancer-related mortality worldwide. Although the utility of noninvasive biomarkers based on circulating cell-free DNA (cfDNA) methylation profiling has been widely recognized, limited studies have been reported so far regarding the dynamics of cfDNA methylome in oral cavity squamous cell carcinoma (OCSCC). It is hypothesized in this study that comparison of methylation profiles in pre- and postsurgery plasma samples will reveal OCSCC-specific prognostic and diagnostic biomarkers. As a strategy to further prioritize tumor-specific targets, top differential methylated regions (DMRs) were called by reanalyzing methylation data from paired tumor and normal tissue collected in the the cancer genome atlas head-neck squamous cell carcinoma (TCGA) head and neck cancer cohort. Matched plasma samples from eight patients with OCSCC were collected at Moffitt Cancer Center before and after surgical resection. Plasma-derived cfDNA was analyzed by cfMBD-seq, which is a high-sensitive methylation profiling assay. Differential methylation analysis was then performed based on the matched samples profiled. In the top 200 HNSCC-specific DMRs detected based on the TCGA data set, a total of 23 regions reached significance in the plasma-based DMR test. The top five validated DMR regions (ranked by the significance in the plasma study) are located in the promoter regions of genes PENK, NXPH1, ZIK1, TBXT, and CDO1, respectively. The genome-wide cfDNA DMR analysis further highlighted candidate biomarkers located in genes SFRP4, SOX1, IRF4, and PCDH17. The prognostic relevance of candidate genes was confirmed by survival analysis using the TCGA data. This study supports the utility of cfDNA-based methylome profiling as a promising noninvasive biomarker source for OCSCC and HNSCC.

The pre-efficacy phase testing for PAfitME™-A behavioral physical activity intervention to manage moderate and severe symptoms among advanced stage cancer patients.

Fatigue and pain are the most frequently reported symptoms among advanced-stage cancer patients. Although physical activity (PA) is known to improve the aforementioned symptoms, few patients demonstrate the physically active behavior that adheres to the clinical guidelines regarding PA. The current article presents an exemplar that used the National Institute of Health's Obesity-Related Behavioral Intervention Trial (ORBIT) model and developed a behavioral intervention known as the personalized Physical Activity intervention with fitness graded Motion Exergames (PAfitME™). There were two phases of testing in the ORBIT model presented in the current paper. In Phase I testing, a standardized exergame prescription was evaluated by an advisory board and a single-case study was used to evaluate the personalized exergame prescription with personalization of the fitness levels. In Phase IIa, a within-group pre- and posttest design was used to evaluate the personalized exergame prescriptions with personalization of the fitness levels, self-efficacy, and variation in fatigue/pain. Subsequently, a complete intervention package was developed in accordance with a logic model, driven from the result of the Phase IIa testing with clinically significant findings. Currently, PAfitME™ is under Phase IIb testing in a randomized clinical trial with a control group. PAfitME™ employs a personalized approach to initiate and promote physically active behavior, to facilitate the management of fatigue and pain in cancer patients. Positive results from an efficacy trial would support the use of PAfitME™ in the management of fatigue and pain in advanced-stage cancer patients.

Upper-airway stimulation for obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea is associated with considerable health risks. Although continuous positive airway pressure (CPAP) can mitigate these risks, effectiveness can be reduced by inadequate adherence to treatment. We evaluated the clinical safety and effectiveness of upper-airway stimulation at 12 months for the treatment of moderate-to-severe obstructive sleep apnea. METHODS: Using a multicenter, prospective, single-group, cohort design, we surgically implanted an upper-airway stimulation device in patients with obstructive sleep apnea who had difficulty either accepting or adhering to CPAP therapy. The primary outcome measures were the apnea-hypopnea index (AHI; the number of apnea or hypopnea events per hour, with a score of ≥15 indicating moderate-to-severe apnea) and the oxygen desaturation index (ODI; the number of times per hour of sleep that the blood oxygen level drops by ≥4 percentage points from baseline). Secondary outcome measures were the Epworth Sleepiness Scale, the Functional Outcomes of Sleep Questionnaire (FOSQ), and the percentage of sleep time with the oxygen saturation less than 90%. Consecutive participants with a response were included in a randomized, controlled therapy-withdrawal trial. RESULTS: The study included 126 participants; 83% were men. The mean age was 54.5 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 28.4. The median AHI score at 12 months decreased 68%, from 29.3 events per hour to 9.0 events per hour (P<0.001); the ODI score decreased 70%, from 25.4 events per hour to 7.4 events per hour (P<0.001). Secondary outcome measures showed a reduction in the effects of sleep apnea and improved quality of life. In the randomized phase, the mean AHI score did not differ significantly from the 12-month score in the nonrandomized phase among the 23 participants in the therapy-maintenance group (8.9 and 7.2 events per hour, respectively); the AHI score was significantly higher (indicating more severe apnea) among the 23 participants in the therapy-withdrawal group (25.8 vs. 7.6 events per hour, P<0.001). The ODI results followed a similar pattern. The rate of procedure-related serious adverse events was less than 2%. CONCLUSIONS: In this uncontrolled cohort study, upper-airway stimulation led to significant improvements in objective and subjective measurements of the severity of obstructive sleep apnea. (Funded by Inspire Medical Systems; STAR ClinicalTrials.gov number, NCT01161420.).

Determining optimal follow-up in the management of human papillomavirus-positive oropharyngeal cancer.

BACKGROUND: Determining the optimal follow-up for patients can help maximize the use of health care resources. This is particularly true in a growing epidemic such as human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV+OPSCC). The objective of the current study was to evaluate time to disease recurrence or late toxicity in this cohort of patients to optimize patient management. METHODS: An institutional database identified 232 patients with biopsy-proven, nonmetastatic HPV+OPSCC who were treated with radiotherapy. A retrospective review was conducted in patients who were followed every 3 months for the first year, every 4 months in year 2, and every 6 months in years 3 to 5. Late toxicity (grade ≥ 3; toxicity was scored based on National Cancer Institute Common Terminology Criteria for Adverse Events [version 4]), locoregional control, distant control, and overall survival were assessed. RESULTS: The median follow-up was 33 months. Based on Radiation Therapy Oncology Group (RTOG) 0129 study risk groupings, patients were either considered to be at low (162 patients; 70%) or intermediate (70 patients; 30%) risk. Concurrent systemic therapy was used in 85% of patients (196 patients). The 3-year locoregional control, distant control, and overall survival rates were 94%, 91%, and 91%, respectively. Late toxicity occurred in 9% of patients (21 patients). Overall, 64% of toxicity and failure events occurred within the first 6 months of follow-up, with a < 2% event incidence noted at each subsequent follow-up. Only 4 patients experienced their first event after 2 years. CONCLUSIONS: HPV+OPSCC has a low risk of disease recurrence and late toxicity after treatment; approximately two-thirds of events occur within the first 6 months of follow-up. These data suggest that it may be reasonable to reduce follow-up in patients with HPV+OPSCC to every 3 months for the first 6 months, every 6 months for the first 2 years, and annually thereafter.

Radiation Therapy is Associated with Improved Outcomes in Merkel Cell Carcinoma.

BACKGROUND: Following wide excision of Merkel cell carcinoma (MCC), postoperative radiation therapy (RT) is typically recommended. Controversy remains as to whether RT can be avoided in selected cases, such as those with negative margins. Additionally, there is evidence that RT can influence survival. METHODS: We included 171 patients treated for non-metastatic MCC from 1994 through 2012 at a single institution. Patients without pathologic nodal evaluation (clinical N0 disease) were excluded to reflect modern treatment practice. The endpoints included local control (LC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS). RESULTS: Median follow-up was 33 months. Treatment with RT was associated with improved 3-year LC (91.2 vs. 76.9 %, respectively; p = 0.01), LRC (79.5 vs. 59.1 %; p = 0.004), DFS (57.0 vs. 30.2 %; p < 0.001), and OS (73 vs. 66 %; p = 0.02), and was associated with improved 3-year DSS among node-positive patients (76.2 vs. 48.1 %; p = 0.035), but not node-negative patients (90.1 vs. 80.8 %; p = 0.79). On multivariate analysis, RT was associated with improved LC [hazard ratio (HR) 0.18, 95 % confidence interval (CI) 0.07-0.46; p < 0.001], LRC (HR 0.28, 95 % CI 0.14-0.56; p < 0.001), DFS (HR 0.42, 95 % CI 0.26-0.70; p = 0.001), OS (HR 0.53, 95 % CI 0.31-0.93; p = 0.03), and DSS (HR 0.42, 95 % CI 0.26-0.70; p = 0.001). Patients with negative margins had significant improvements in 3-year LC (90.1 vs. 75.4 %; p < 0.001) with RT. Deaths not attributable to MCC were relatively evenly distributed between the RT and no RT groups (28.5 and 29.3 % of patients, respectively). CONCLUSIONS: RT for MCC was associated with improved LRC and survival. RT appeared to be beneficial regardless of margin status.

Multidisciplinary Management of Salivary Gland Cancers.

BACKGROUND: Salivary carcinomas are a rare group of biologically diverse neoplasms affecting the head and neck. The wide array of different histological entities and clinical presentations has historically limited attempts to establish well-defined treatment algorithms. In general, low-risk lesions can be managed with a single treatment modality, whereas advanced lesions require a more complex, multidisciplinary approach. METHODS: The relevant literature was reviewed, focusing on diagnostic and treatment algorithms for salivary malignancies. RESULTS: Salivary carcinomas with high-risk features require an aggressive treatment approach with complete surgical resection, neck dissection to appropriate cervical lymph-node basins, and postoperative radiotherapy. CONCLUSIONS: The heterogeneity of salivary neoplasms represents a unique clinical challenge. Despite the multidisciplinary management paradigm detailed in this review, outcomes for advanced disease are unsatisfactory. Future progress will likely require the addition of novel systemic therapeutic strategies.

Both tumor depth and diameter are predictive of sentinel lymph node status and survival in Merkel cell carcinoma.

BACKGROUND: The purposes of this study were 1) to determine the impact of primary tumor-related factors on the prediction of the sentinel lymph node (SLN) status and 2) to identify clinical and pathologic factors associated with survival in Merkel cell carcinoma (MCC). METHODS: An institutional review board-approved, retrospective review of patients with MCC treated between 1988 and 2011 at a single center was performed. Patients were categorized into 5 groups: 1) negative SLN, 2) positive SLN, 3) clinically node-negative but SLN biopsy not performed, 4) regional nodal disease without a known primary tumor, and 5) primary MCC with synchronous clinically evident regional nodal disease. Factors predictive of the SLN status were analyzed with logistic regressions, and overall survival (OS) and disease-specific survival (DSS) were analyzed with Cox models and competing risk models assuming proportional hazards, respectively. RESULTS: Three hundred seventy-five patients were analyzed, and 70% were male; the median age was 75 years. The median tumor diameter was 1.5 cm (range, 0.2-12.5 cm), and the median tumor depth was 4.8 mm (range, 0.3-45.0 mm). One hundred ninety-one patients underwent SLN biopsy, and 59 (31%) were SLN-positive. Increasing primary tumor diameter and increasing tumor depth were associated with SLN positivity (P = .007 and P = .017, respectively). Age and sex were not associated with the SLN status. Immunosuppression, increasing tumor diameter, and increasing tumor depth were associated with worse OS (P = .007, P = .003, and P = .025, respectively). DSS differed significantly by group and was best for patients with a negative SLN and worst for those with primary MCC and synchronous clinically evident nodal disease (P = .018). CONCLUSION: For patients with MCC, increasing primary tumor diameter and increasing tumor depth are independently predictive of a positive SLN, worse OS, and worse DSS. Tumor depth should be routinely reported when primary MCC specimens are being evaluated histopathologically.

Robotic-Assisted Surgery in the Head and Neck.

BACKGROUND: Robotic surgery was first used in medicine in the 1980s for laparoscopic surgery. Since then, several developments have been made in the use of robotic surgery for patients with head and neck cancer. METHODS: A review was performed of the literature on robotic surgery in patients with head and neck cancer. The various sites of application are discussed in depth as well as the functional and oncological outcomes associated with the most common application of transoral robotic surgery (TORS). RESULTS: Robotic surgery has been used in all aspects of head and neck surgery. The results from early studies of TORS have shown at least equivalent functional and oncological outcomes. CONCLUSIONS: Robotic surgery has feasible utility in patients with head and neck cancer; moreover, in several circumstances it may provide superior cosmetic, functional, and oncological outcomes than conventional methods.

Lingual traction to facilitate fiber-optic intubation of difficult airways: a single-anesthesiologist randomized trial.

PURPOSE: Flexible fiber-optic bronchoscope-guided orotracheal intubation is a valuable technique with demonstrated benefits in the management of difficult airways. Despite its popularity with anesthesia providers, the technique is not fail-safe and airway-related complications secondary to failed intubation attempts remain an important problem. We sought to determine the effect of incorporating lingual traction on the success rate of fiber-optic bronchoscope-guided intubation in patients with anticipated difficult airways. METHODS: In this prospective, randomized, cohort study, we enrolled 91 adult patients with anticipated difficult airways scheduled for elective surgery to undergo fiber-optic bronchoscope-guided orotracheal intubation alone or with lingual traction by an individual anesthesiologist after induction of general anesthesia and neuromuscular blockade. A total of 78 patients were randomized: 39 patients to the fiber-optic bronchoscope-guided intubation with lingual traction group and 39 patients to the fiber-optic bronchoscope-guided intubation alone group. The primary endpoint was the rate of successful first attempt intubations. The secondary outcome was sore throat grade on post-operative day 1. RESULTS: Fiber-optic intubation with lingual traction compared to fiber-optic intubation alone resulted in a higher success rate (92.3 vs. 74.4 %, χ (2) = 4.523, p = 0.033) and greater odds for successful first attempt intubation (OR 4.138, 95 % CI 1.041-16.444, p = 0.044). Sore throat severity on post-operative day 1 was not significantly different but trended towards worsening grades with lingual traction. CONCLUSIONS: In this study, lingual traction was shown to be a valuable maneuver for facilitating fiber-optic bronchoscope-guided intubation in the management of patients with anticipated difficult airways.

Video-assisted thoracoscopic surgery retrieval of a migrated unilateral hypoglossal nerve stimulator sensor lead.

Obstructive sleep apnea is a common chronic condition typically treated with positive airway pressure. However, many patients have difficulty with adherence to this therapy, and for some, implantation of a hypoglossal nerve stimulator has become an option. Though device implantation is generally well-tolerated, a minority of patients will experience serious adverse events. Here we report the unusual complication of the sensor lead migrating to the costophrenic angle and invading the pleural space. Nine months after original implantation, the sensor lead malfunctioned and was found to be displaced. Initial explantation and reimplantation of a new device resulted in the inability to find a portion of the lead. Reimaging showed the missing lead at the costophrenic angle, and the patient underwent thoracoscopic removal. He resumed therapy with the new device without difficulty. This case demonstrates the ability of the lead to migrate far from the implantation site, which has rarely been reported.

Cutaneous angiosarcoma: a single-institution experience.

BACKGROUND: Cutaneous angiosarcoma (CAS) is a rare, aggressive vascular sarcoma with a poor prognosis, historically associated with 5-year overall survival (OS) rates between 10 and 30 %. METHODS: This is a single-institution retrospective review of patients treated for CAS from 1999-2011. Demographics, primary tumor characteristics, treatment, and outcomes were analyzed. RESULTS: A total of 88 patients were identified (median age 70 years and 57 % female). Median tumor size was 3 cm. Median follow-up was 22 months. The 5-year OS and recurrence-free survival (RFS) were 35.2 and 32.3 %, respectively; median was 22.1 months. Also, 36 patients (41 %) received surgery alone, 7 (8 %) received XRT alone, and 41 (47 %) received surgery and XRT. Of the 67 of 88 patients who were disease-free after treatment, 33 (50 %) recurred (median of 12.3 months). Surgery alone had the highest 5-year OS (46.9 %) and RFS (39.9 %) (p = ns). Four presentation groups were identified: (1) XRT-induced, n = 30 (34 %), 26 of 30 occurred in females with a prior breast cancer, (2) sporadic CAS on head and neck (H/N), n = 38, (3) sporadic CAS on trunk/extremities, n = 13, and (4) Stewart-Treves n = 7. Those with trunk/extremity CAS had the highest 5-year OS (64.8 %), with H/N CAS having the worst 5-year OS (21.5 %). On MV analysis, only tumor size <5 cm correlated with improved OS (p = 0.014). DISCUSSION: In this large series, there appears to be a better overall prognosis than historically reported, especially in Stewart-Treves and CAS on trunk or extremities. While surgery alone was associated with better OS and RFS compared with other treatment modalities, this was not statistically significant. Tumor size was a significant prognostic factor for OS.

Rare treatment of radiation induced carotid pseudoaneurysm and ensuing carotid blowout syndrome with placement of multiple contiguous endovascular stents: a case report.

Cervical radiotherapy for treatment of head and neck cancer can result in the delayed carotid vasculopathy. Surgical management for an ensuing hemorrhage is challenging due to the associated high mortality and morbidity. We present a case of a relative rapid formation of common carotid pseudoaneurysm formation with subsequent carotid blowout syndrome in previously irradiated neck. Successful treatment in our patient is highlighted by the fact that multiple, contiguous endovascular stents were placed emergently to obtain control of pseudoaneurysm rupture.

Telehealth Interventions in Head and Neck Cancer Patients: A Systematic Review.

BACKGROUND: Head and neck cancer (HNC) and its treatments often result in adverse effects that impair a patient's quality of life. Although intensive rehabilitative strategies can be used, their applicability can be limited due to patient-specific and socioeconomic barriers. Telehealth interventions represent a possible novel approach to increase access to these services and improve posttreatment quality of life in the HNC population. OBJECTIVE: The objective of this systematic review was to identify studies investigating telemedicine-based interventions for HNC patients to determine whether there is a consensus concerning the cost-effectiveness, clinical utility, and accessibility of this model for rehabilitation. METHODS: PubMed, EMBASE, Web of Science, and CINAHL were used to identify literature without time limit for publication. A critical appraisal of individual sources was conducted by 2 reviewers. Sixteen studies met inclusion criteria. RESULTS: Studies related to telehealth interventions in the HNC population are limited. Salient themes included feasibility of telehealth as an intervention, effects on self-management and knowledge, impact on quality of life, physical and psychiatric symptoms, and cost. CONCLUSION: Although the current literature presents promising data, indicating that telehealth interventions may be both effective and cost-efficient in the management of HNC patients, more research is needed to definitively elucidate their role in management. IMPLICATIONS FOR PRACTICE: Telehealth interventions are valuable for clinicians as an alternative to expand access to care across the cancer continuum, to strengthen patients' knowledge and consequently their self-management, and to provide continuity of services as well as for remote monitoring of symptoms and response to treatment.

How do i salvage that flap?; An evidence-based primer on salvage techniques for head & neck microvascular free flaps.

Interventional strategies for dealing with microvascular free flap failure are varied among institutions and even individual surgeons. This systematic review aims to identify the published methods for salvaging a failing free flap and provide surgeons with a comprehensive toolset for successful intervention. A title and abstract search of the PubMed, Embase, and Web of Science databases was performed. 1694 abstracts were screened by three reviewers according to Prisma guidelines. 62 full text articles meeting inclusion criteria detailed techniques which were separated into the categories of thrombectomy, thrombolysis, leech therapy, vascular fistula, and an "other" category outlining techniques which did not fit into the prior framework. Assessment of the efficacy of individual salvage techniques is limited due to limited empirical data, however, the approach to successful salvage should be based on timely identification of flap compromise, followed by the implementation of one or several of the aforementioned techniques.

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.

Endoscopic lumen restoration for obstructive aphagia: outcomes of a 25-year experience.

BACKGROUND: After chemoradiation therapy for head/neck cancer, some patients develop strictures that progress to complete pharyngoesophageal occlusion. Total lumen occlusion is less often due to other conditions. Enteral access (enterostomy tube) and good nutritional status tend to minimize the significance of dysphagia and therefore may mask recognition of impending complete lumen occlusion. OBJECTIVE: Review outcomes of a 25-year experience with endoscopic lumen restoration (ELR) in 30 patients. DESIGN: Retrospective, case review study. SETTING: Two tertiary-care referral centers. PATIENTS: This study involved 30 consecutive patients referred for obstructive aphagia due to complete lumen occlusion, primarily after chemoradiation therapy for head/neck cancer. INTERVENTION: Antegrade and retrograde endoscopy with tri-plane fluoroscopy for penetrating the occluded segment, serial retrograde and antegrade dilations, plus swallowing rehabilitation therapy. MAIN OUTCOME MEASUREMENTS: Restoration of lumen patency, swallowing function, and removal of enteral feeding tube. RESULTS: ELR was successful in 30 patients in 31 of 33 attempts (93%). Return to soft to regular diet was achieved in 15 of 30 patients (50%), and fluids to pureed food with partial percutaneous endoscopic gastrostomy nutrition was achieved in 5 of 30 patients (17%). Ten of 30 patients (33%) were considered unsafe for oral feeding because of oropharyngeal neuromotor deficits. Complications occurred in 5 of 30 patients (17%), with no prolonged sequelae, deaths, or surgery, but two stents were placed for anastomotic fistulas. The median duration of follow-up was 22.75 months. LIMITATIONS: Retrospective, case review study. CONCLUSION: ELR by using tri-plane fluoroscopic guidance with antegrade and retrograde endoscopy and serial dilations allows lumen restoration and swallowing to some degree in a majority of patients. Engagement of a core team of specialists can provide optimal restoration of swallowing function.

Management of Pediatric Obstructive Sleep Apnea After Failed Tonsillectomy and Adenoidectomy.

Pediatric obstructive sleep apnea (OSA) represents a different entity from its adult counterpart and therefore requires a different therapeutic approach. Adenotonsillectomy (AT) is the primary treatment of pediatric OSA, and evidence shows it is very effective. However, there is a growing understanding that residual OSA is common, and next steps for patients who fail primary AT are less certain. This article reviews current methods of evaluating and treating these complex patients.

Similar effect of hypoglossal nerve stimulation for obstructive sleep apnea in 5 disease severity categories.

STUDY OBJECTIVES: Data on adherence and outcome of upper airway stimulation (UAS) for patients with obstructive sleep apnea (OSA) are collected in an international registry (ADHERE). Previous publications report significant improvement in self-reported and objective OSA outcomes, durable effectiveness, and high adherence. Debate remains whether the effectiveness of UAS is influenced by preoperative OSA severity; therefore, we aimed to evaluate this using data from the ADHERE Registry. METHODS: ADHERE is a postmarket, ongoing, international multicenter registry. Adult patients were included if they had undergone UAS implantation and had at least 1 follow-up visit recorded in the database on June 8, 2021. We divided the patients into 5 subgroups, based on OSA severity at baseline (AHI in events/h): subgroup 1 (0-15), 2 (15-30), 3 (≥ 30-50), 4 (> 50-65), and 5 (> 65). We compared results regarding objective and self-reported treatment outcomes. RESULTS: A total of 1,963 patients were included. Twelve months after implantation, there was a significant (P < .0001) improvement in objective sleep parameters in all subgroups with an AHI above 15 events/h. Patients in subgroup 1 had the lowest AHI at the final visit and the AHI reduction in patients in subgroup 5 was the largest (P < .0001). No significant difference was found between the subgroups in overall treatment success (66.6%) and improvement in self-reported outcomes. CONCLUSIONS: Our results suggest that UAS is an effective treatment for patients with an AHI ≥ 15 events/h, independent of preoperative OSA severity. Self-reported outcomes and treatment success did not differ significantly between the 5 subgroups. These results clearly support that the indication of UAS could be broadened for patients with an AHI above 65 events/h, which, to date, is not common practice. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Adherence and Outcome of Upper Airway Stimulation (UAS) for OSA International Registry (ADHERE Registry); Identifier: NCT02907398; URL: https://www.clinicaltrials.gov/ct2/show/NCT02907398. CITATION: Bosschieter PFN, de Vries N, Mehra R, et al. Similar effect of hypoglossal nerve stimulation for obstructive sleep apnea in 5 disease severity categories. J Clin Sleep Med. 2022;18(6):1657-1665.

The Impact of the Affordable Care Act on Insurance Coverage and Stage Among Head and Neck Squamous Cell Carcinoma Patients.

The purpose was to examine the change in percent uninsured and if there is change in T-stage, N-stage and overall-stage among nonelderly patients with newly diagnosed head and neck squamous cell carcinoma after the Affordable Care Act (ACA). The National Cancer Database was used for this study. Patients were divided between pre-ACA and post-ACA implementation with stratification between areas of ACA expansion versus non-expansion. A quasi-experimental difference-in-difference study design was undertaken. A total of 15,037 patients met the inclusion criteria. Between the pre-ACA and post-ACA periods, there was increase in proportion of percent insured with Medicaid coverage in patients residing in expansion region. There was a decrease in the proportion of patients who had advanced Tumor stage and Nodal stage decreased after implementation of ACA. With the implementation of ACA expansion, there is increased Medicaid coverage, corresponding to a decreased proportion of patients presenting with advanced T-stage and N-stage.

Mechanism regulating reactive oxygen species in tumor-induced myeloid-derived suppressor cells.

Myeloid-derived suppressor cells (MDSC) are a major component of the immune suppressive network described in cancer and many other pathological conditions. Recent studies have demonstrated that one of the major mechanisms of MDSC-induced immune suppression is mediated by reactive oxygen species (ROS). However, the mechanism of this phenomenon remained unknown. In this study, we observed a substantial up-regulation of ROS by MDSC in all of seven different tumor models and in patients with head and neck cancer. The increased ROS production by MDSC is mediated by up-regulated activity of NADPH oxidase (NOX2). MDSC from tumor-bearing mice had significantly higher expression of NOX2 subunits, primarily p47(phox) and gp91(phox), compared with immature myeloid cells from tumor-free mice. Expression of NOX2 subunits in MDSC was controlled by the STAT3 transcription factor. In the absence of NOX2 activity, MDSC lost the ability to suppress T cell responses and quickly differentiated into mature macrophages and dendritic cells. These findings expand our fundamental understanding of the biology of MDSC and may also open new opportunities for therapeutic regulation of these cells in cancer.