Daily Exposure to Mild Intermittent Hypoxia Reduces Blood Pressure in Male Patients with Obstructive Sleep Apnea and Hypertension.

Rationale: Daily exposure to mild intermittent hypoxia (MIH) may elicit beneficial cardiovascular outcomes. Objectives: To determine the effect of 15 days of MIH and in-home continuous positive airway pressure treatment on blood pressure in participants with obstructive sleep apnea and hypertension. Methods: We administered MIH during wakefulness 5 days/week for 3 weeks. The protocol consisted of twelve 2-minute bouts of hypoxia interspersed with 2 minutes of normoxia. End-tidal carbon dioxide was maintained 2 mm Hg above baseline values throughout the protocol. Control participants were exposed to a sham protocol (i.e., compressed air). All participants were treated with continuous positive airway pressure over the 3-week period. Results are mean ± SD. Measurements and Main Results: Sixteen male participants completed the study (experimental n = 10; control n = 6). Systolic blood pressure at rest during wakefulness over 24 hours was reduced after 15 days of MIH (142.9 ± 8.6 vs. 132.0 ± 10.7 mm Hg; P < 0.001), but not following the sham protocol (149.9 ± 8.6 vs. 149.7 ± 10.8 mm Hg; P = 0.915). Thus, the reduction in blood pressure from baseline was greater in the experimental group compared with control (-10.91 ± 4.1 vs. -0.17 ± 3.6 mm Hg; P = 0.003). Modifications in blood pressure were accompanied by increased parasympathetic and reduced sympathetic activity in the experimental group, as estimated by blood pressure and heart rate variability analysis. No detrimental neurocognitive and metabolic outcomes were evident following MIH. Conclusions: MIH elicits beneficial cardiovascular and autonomic outcomes in males with OSA and concurrent hypertension. Clinical trial registered with www.clinicaltrials.gov (NCT03736382).

Telemedicine trends at a comprehensive cancer center during the first wave of the COVID-19 pandemic.

INTRODUCTION: This article reports on the effects of an early outbreak during the COVID-19 pandemic on visit volume and telehealth use by various specialists at a comprehensive cancer center. MATERIALS AND METHODS: The number of on-site and telehealth visits (THV) for medical and surgical specialties were obtained from scheduling software. RESULTS: Total visits were most drastically limited in April 2020 to a low point of 3139; THV made up 28% of all visits. For head and neck surgery, THV made up 54% and 30% of visits in April and May, respectively. Other specialties, such as psychiatry and palliative care, had higher levels of THV. For most specialties, the rebound in June through September did not make up for visits lost during the outbreak, and fiscal year  (FY) 2020 had a 9% loss from FY 2019 with 5786 fewer total annual visits across all specialties. CONCLUSIONS: While telemedicine was a helpful part of this cancer center's response to the initial COVID-19 surge, it was not able to replace the in-person services offered at the same center. The main strategy of physicians at this cancer center was to defer care, with telemedicine being an auxiliary response.

Fellow selection protocols in sleep surgery: a national survey of sleep surgery program directors.

PURPOSE: To determine the factors that sleep medicine/surgery fellowship program directors look for in applicants. METHODS: Program directors from 9 sleep medicine/surgery fellowship programs in the USA were sent an anonymous online survey. They were asked to select the five most important academic factors (of a list of 17) when evaluating potential fellowship candidates, then rank those five in order of importance. They were then asked to do the same for the most important subjective criteria (of a list of 12). RESULTS: Eight of 10 survey responses met inclusion criteria. Of the academic factors, strength of letters of recommendation, reputation of letter writer, and letters from sleep surgeons ranked highest. As for the subjective criteria, faculty assessment of the applicant on interview was ranked highest, followed by initiative and personality "fit" with the program. The reputation of an applicant's residency was ranked as more important than the reputation of their medical school. An applicant's performance in residency was assessed as more predictive of their performance in fellowship than performance during the interview process or position on the rank order list for the match. Only one program has a United States Medical Licensing Examination (USMLE) Step, and a different program has an Otolaryngology Training Examination (OTE) score cutoff. CONCLUSION: Letters of recommendation and interview are the most important factors in the selection process for hybrid sleep medicine and surgery fellowship programs, followed by research and residency program reputation. Sleep surgery-specific experience is helpful.

An update on the status of nerve monitoring for thyroid/parathyroid surgery.

PURPOSE OF REVIEW: Recurrent laryngeal nerve (RLN) injury is one of the most common and serious complications associated with thyroid and parathyroid surgery. Although routine visual identification of the RLN is considered the current standard of care, the role of intraoperative neuromonitoring (IONM) of the RLN is more controversial. RECENT FINDINGS: Despite initial enthusiasm that IONM might substantially reduce the rate of RLN injury, most studies failed to show a significant difference in the rate of RLN injury when the use of IONM was compared with visualization of the RLN alone. However, a small number of investigators have reported statistically significant differences in the rates of nerve injury when IONM is used to augment visualization alone, particularly in certain high-risk situations. Despite a lack of conclusive data showing benefit, the use of IONM as an adjunct to visual identification of the RLN has gained increasing acceptance among surgeons. IONM remains an excellent tool to help verify the identity of the RLN, confirm its functional integrity, and pinpoint the site of nerve injury in the event of dysfunction. SUMMARY: The utility of IONM in reducing the rate of RLN injury is largely unproven and remains controversial. However, the use of IONM may be helpful in certain high-risk cases. Promising new technology, such as vagal nerve monitoring, may allow more real-time monitoring of the functional integrity of the RLN and allow the surgeon to react in a timely manner to evolving dysfunction in order to abort maneuvers that may risk definitive injury.

Nutritional Correlates of Human Oral Microbiome.

BACKGROUND: Despite many potential effects of the oral microbiome on oral and systemic health, scant information is available regarding the associations between diet and the oral microbiome. METHODS: Oral rinse DNA samples from 182 participants in a population-based case-control study for colorectal cancer were used to amplify a V3-V4 region of bacterial 16S rRNA gene. The amplicons were sequenced using Illumina MiSeq paired end chemistry on 2 runs, yielding approximately 33 million filtered reads that were assigned to bacterial classes. Relative abundances of each class and family as well microbial diversity/richness indices were correlated with selected dietary intakes from a food frequency questionnaire. RESULTS: Saturated fatty acids (SFAs) and vitamin C intakes were consistently correlated with alpha (within-subjects) diversity indexes in both richness and diversity. SFA intake was positively correlated with relative abundance of betaproteobacteria and fusobacteria. Vitamin C and other vitamins with correlated intakes-for example, the B vitamins and vitamin E-exhibited positive correlations with fusobacteria class, its family Leptotrichiaceae and a clostridia family Lachnospiraceae. In addition, glycemic load was positively correlated with Lactobacillaceae abundance. CONCLUSION: The observed associations in this study were modest. However, the results suggest that the effects of diets are likely to be habitat specific, and observations from the gut microbiome are not transferrable to the oral microbiome. Further studies are warranted, incorporating a range of host biomarkers, such as cytohistological, molecular, or biochemical measurements, in order to address biological consequences of these dietary intakes in human oral health.

Ceramide synthase inhibitor fumonisin B1 inhibits apoptotic cell death in SCC17B human head and neck squamous carcinoma cells after Pc4 photosensitization.

The sphingolipid ceramide modulates stress-induced cell death and apoptosis. We have shown that ceramide generated via de novo sphingolipid biosynthesis is required to initiate apoptosis after photodynamic therapy (PDT). The objective of this study was to define the role of ceramide synthase (CERS) in PDT-induced cell death and apoptosis using fumonisin B1 (FB), a CERS inhibitor. We used the silicon phthalocyanine Pc4 for PDT, and SCC17B cells, as a clinically-relevant model of human head and neck squamous carcinoma. zVAD-fmk, a pan-caspase inhibitor, as well as FB, protected cells from death after PDT. In contrast, ABT199, an inhibitor of the anti-apoptotic protein Bcl2, enhanced cell killing after PDT. PDT-induced accumulation of ceramide in the endoplasmic reticulum and mitochondria was inhibited by FB. PDT-induced Bax translocation to the mitochondria and cytochrome c release were also inhibited by FB. These novel data suggest that PDT-induced cell death via apoptosis is CERS/ceramide-dependent.

Risk stratification based on thyroid cytology: can we rely on national data?

PURPOSE: Determine correlation of malignancy rates between fine needle aspiration (FNA) biopsy and surgical specimen in an urban academic environment. METHODS: Retrospective review at an academic medical center of fine needle aspiration biopsies and surgical specimens in a head and neck otolaryngology practice between 2000 and 2012. RESULTS: Of the 74 biopsies diagnosed as follicular lesion, 34 (45.9%) were malignant. Of the 45 biopsies diagnosed as follicular neoplasm, 22 (48.9%) were malignant. These results are significantly higher than the average risk of malignancy cited by the American Thyroid Association of 5%-10% and 20%-30% for follicular lesions and neoplasms respectively. CONCLUSIONS: The rate of malignancy based on a FNA diagnosis of indeterminate cytology (follicular lesion or follicular neoplasm) can vary greatly among different institutions. Thyroid surgeons should be aware of their local pathology practices to better guide therapy and counsel patients.

Total Laryngectomy for Respiratory Complications From Advanced Duchenne Muscular Dystrophy.

Due to respiratory weakness, late-stage Duchenne muscular dystrophy (DMD) patients may suffer from chronic aspiration, which is sometimes treated using tracheostomy. However, definitive laryngectomy has not been described in the literature as an aspiration prevention modality in DMD, especially in patients with contraindications to tracheostomy. A case is presented for a patient with advanced stage Duchenne muscular dystrophy suffering from chronic aspiration pneumonia and excessive oral secretions who became ventilator dependent. A tracheostomy was placed, but was noted to have excessive secretions and high cuff pressures, which have been known to be associated with worsened swallow dysfunction as well as tracheoinnominate fistula. The patient therefore was considered for total laryngectomy, which he underwent successfully. Post-operatively, the patient was noted to have improved subjective quality of life, engaged in an oral diet, and had less secretions surrounding his tracheostoma post-operatively. Aspiration prevention surgeries are done to improve quality of life by improving oral intake, decreasing the need for frequent suctioning, and can sometimes allow for speech. It is important to consider quality of life for DMD patients as more of these patients are living into their 30s with the aid of mechanical ventilation. Laryngectomy is a surgery that can definitively correct chronic aspiration while allowing for oral intake. Laryngoscope, 2024.

Racial differences in upper airway collapsibility and loop gain in young adult males.

STUDY OBJECTIVES: Previous studies reported that the apnea-hypopnea index was similar in young adult Black and White participants. However, whether this similarity reflects an analogous combination of apneas and hypopneas is unknown. Likewise, the physiological mechanisms underlying this similarity has not been explored. METHODS: 60 Black and 48 White males completed the study. After matching for age and body mass index, 41 participants remained in each group. All participants completed a sleep study. Subsequently, standard sleep indices along with loop gain and the arousal threshold were determined. In addition, airway collapsibility (24 of 60 and 14 of 48 participants) and the hypoxic ventilatory response during wakefulness (30 of 60 and 25 of 48 participants) was measured. RESULTS: The apnea-hypopnea index was similar in Blacks and Whites (p = .140). However, the index was comprised of more apneas (p = .014) and fewer hypopneas (p = .025) in Black males. These modifications were coupled to a reduced loop gain (p = .0002) and a more collapsible airway (p = .030). These differences were independent of whether or not the groups were matched. For a given hypoxic response, loop gain was reduced in Black compared to White males (p = .023). CONCLUSIONS: Despite a similar apnea-hypopnea index, more apneas and fewer hypopneas were evident in young adult Black compared to White males. The physiological mechanisms that contribute to these events were also different between groups. Addressing these differences may be important when considering novel therapeutic approaches to eliminate apnea in Black and White participants.

Divergent Ventilatory and Blood Pressure Responses are Evident Following Repeated Daily Exposure to Mild Intermittent Hypoxia in Males with OSA and Hypertension.

Introduction: Resting minute ventilation and ventilation during and following hypoxia may be enhanced following daily exposure to mild intermittent hypoxia (MIH). In contrast, resting systolic blood pressure (SBP) is reduced following daily exposure to MIH. However, it is presently unknown if the reduction in resting SBP following daily exposure, is coupled with reduced SBP responses during and after acute exposure to MIH. Methods: Participants with obstructive sleep apnea (OSA) and hypertension (n = 10) were exposed to twelve 2-min bouts of MIH (oxygen saturation-87%)/day for 15 days. A control group (n = 6) was exposed to a sham protocol during which compressed air (i.e., FIO2 = 0.21) was inspired in place of MIH. Results: The hypoxic ventilatory response (HVR) and hypoxic systolic blood pressure response (HSBP) increased from the first to the last hypoxic episode on the initial (HVR: 0.08 ± 0.02 vs. 0.13 ± 0.02 L/min/mmHg, p = 0.03; HSBP: 0.13 ± 0.04 vs. 0.37 ± 0.06 mmHg/mmHg, p < 0.001) and final (HVR: 0.10 ± 0.01 vs. 0.15 ± 0.03 L/min/mmHg, p = 0.03; HSBP: 0.16 ± 0.03 vs. 0.41 ± 0.34 mmHg/mmHg, p < 0.001) day. The magnitude of the increase was not different between days (p ≥ 0.83). Following exposure to MIH, minute ventilation and SBP was elevated compared to baseline on the initial (MV: 16.70 ± 1.10 vs. 14.20 ± 0.28 L/min, p = 0.01; SBP: 167.26 ± 4.43 vs. 151.13 ± 4.56 mmHg, p < 0.001) and final (MV: 17.90 ± 1.25 vs. 15.40 ± 0.77 L/min, p = 0.01; SBP: 156.24 ± 3.42 vs. 137.18 ± 4.17 mmHg, p < 0.001) day. The magnitude of the increases was similar on both days (MV: 3.68 ± 1.69 vs. 3.22 ± 1.27 L/min, SBP: 14.83 ± 2.64 vs. 14.28 ± 1.66 mmHg, p ≥ 0.414). Despite these similarities, blood pressure at baseline and at other time points during the MIH protocol was reduced on the final compared to the initial day (p ≤ 0.005). Conclusion: The ventilatory and blood pressure responses during and following acute MIH were similar on the initial and final day of exposure. Alternatively, blood pressure was down regulated, while ventilation was similar at all time points (i.e., baseline, during and following MIH) after daily exposure to MIH.

African American race as a risk factor associated with a second primary lung cancer after initial primary head and neck cancer.

BACKGROUND: Initial primary head and neck cancer (IPHNC) is associated with second primary lung cancer (SPLC). We studied this association in a population with a high proportion of African American (AA) patients. METHODS: Patients with IPHNC and SPLC treated between 2000 and 2017 were reviewed for demographic, disease, and treatment-related characteristics and compared to age-and-stage-matched controls without SPLC. Logistic and Cox regression models were used to analyze the relationship of these characteristics with the development of SPLC and overall survival (OS). RESULTS: Eighty-seven patients and controls were compared respectively. AA race was associated with a significantly higher risk of developing SPLC (OR 2.92, 95% CI 1.35-6.66). After correcting for immortal time bias, patients with SPLC had a significantly lower OS when compared with controls (HR 0.248, 95% CI 0.170-0.362). CONCLUSIONS: We show that AA race is associated with an increased risk of SPLC after IPHNC; reasons of this increased risk warrant further investigation.

Comparison of Traditional Upper Airway Surgery and Upper Airway Stimulation for Obstructive Sleep Apnea.

OBJECTIVE: To compare patients with moderate-severe obstructive sleep apnea (OSA) undergoing traditional single and multilevel sleep surgery to those undergoing upper airway stimulation (UAS). STUDY DESIGN: Case control study comparing retrospective cohort of patients undergoing traditional sleep surgery to patients undergoing UAS enrolled in the ADHERE registry. SETTING: 8 multinational academic medical centers. SUBJECTS AND METHODS: 233 patients undergoing prior single or multilevel traditional sleep surgery and meeting study inclusion criteria were compared to 465 patients from the ADHERE registry who underwent UAS. We compared preoperative and postoperative demographic, quality of life, and polysomnographic data. We also evaluated treatment response rates. RESULTS: The pre and postoperative apnea hypopnea index (AHI) was 33.5 and 15 in the traditional sleep surgery group and 32 and 10 in the UAS group. The postoperative AHI in the UAS group was significantly lower. The pre and postoperative Epworth sleepiness scores (ESS) were 12 and 6 in both the traditional sleep surgery and UAS groups. Subgroup analysis evaluated those patients undergoing single level palate and multilevel palate and tongue base traditional sleep surgeries. The UAS group had a significantly lower postoperive AHI than both traditional sleep surgery subgroups. The UAS group had a higher percentage of patients reaching surgical success, defined as a postoperative AHI <20 with a 50% reduction from preoperative severity. CONCLUSION: UAS offers significantly better control of AHI severity than traditional sleep surgery. Quality life improvements were similar between groups.

Drug-Induced Sleep Endoscopy and Hypoglossal Nerve Stimulation Outcomes: A Multicenter Cohort Study.

OBJECTIVES/HYPOTHESIS: To determine the association between findings of blinded reviews of preoperative drug-induced sleep endoscopy (DISE) and outcomes of hypoglossal nerve stimulation (HNS) for obstructive sleep apnea (OSA). STUDY DESIGN: Cohort study. METHODS: A retrospective, multicenter cohort study of 343 adults who underwent treatment of OSA with HNS from 10 academic medical centers was performed. Preoperative DISE videos were scored by four blinded reviewers using the VOTE Classification and evaluation of a possible primary structure contributing to airway obstruction. Consensus DISE findings were examined for an association with surgical outcomes based on therapy titration polysomnogram (tPSG). Treatment response was defined by a decrease of ≥50% in the apnea-hypopnea index (AHI) to <15 events/hour. RESULTS: Study participants (76% male, 60.4 ± 11.0 years old) had a body mass index of 29.2 ± 3.6 kg/m2 . AHI decreased (35.6 ± 15.2 to 11.0 ± 14.1 events/hour; P < .001) on the tPSG, with a 72.6% response rate. Complete palate obstruction (vs. none) was associated with the greatest difference in AHI improvement (-26.8 ± 14.9 vs. -19.2 ± 12.8, P = .02). Complete (vs. partial/none) tongue-related obstruction was associated with increased odds of treatment response (78% vs. 68%, P = .043). Complete (vs. partial/none) oropharyngeal lateral wall-related obstruction was associated with lower odds of surgical response (58% vs. 74%, P = .042). CONCLUSIONS: The DISE finding of primary tongue contribution to airway obstruction was associated with better outcomes, whereas the opposite was true for the oropharyngeal lateral walls. This study suggests that the role for DISE in counseling candidates for HNS extends beyond solely for excluding complete concentric collapse related to the velum. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1676-1682, 2021.

Intratumoral delivery of docetaxel enhances antitumor activity of Ad-p53 in murine head and neck cancer xenograft model.

PURPOSE: The aim of this study is to determine the ability of intratumorally delivered docetaxel to enhance the antitumor activity of adenovirus-mediated delivery of p53 (Ad-p53) in murine head and neck cancer xenograft model. MATERIALS AND METHODS: A xenograft head and neck squamous cell carcinoma mouse model was used. Mice were randomized into 4 groups of 6 mice receiving 6 weeks of biweekly intratumoral injection of (a) diluent, (b) Ad-p53 (1 x 10(10) viral particles per injection), (c) docetaxel (1 mg/kg per injection), and (d) combination of Ad-p53 (1 x 10(10) viral particles per injection) and docetaxel (1 mg/kg per injection). Tumor size, weight, toxicity, and overall and disease-free survival rates were determined. RESULTS: Intratumoral treatments with either docetaxel alone or Ad-p53 alone resulted in statistically significant antitumor activity and improved survival compared with control group. Furthermore, combined delivery of Ad-p53 and docetaxel resulted in a statistically significant reduction in tumor weight when compared to treatment with either Ad-p53 or docetaxel alone. CONCLUSION: Intratumoral delivery of docetaxel enhanced the antitumor effect of Ad-p53 in murine head and neck cancer xenograft model. The result of this preclinical in vivo study is promising and supports further clinical testing to evaluate efficacy of combined intratumoral docetaxel and Ad-p53 in treatment of head and neck cancer.

Assessment and Management of Postoperative Pain Associated with Sleep Apnea Surgery.

A literature review was conducted regarding the assessment and treatment of postoperative pain following surgery for obstructive sleep apnea (OSA). Given the risks of opioid use by patients with OSA, special attention to opioid risk reduction and avoidance is warranted in this population. The results of this review demonstrate the existence of a body of evidence that supports the use of nonopioid analgesics and nonpharmacologic approaches pain management. Strategies for managing postoperative pain should emphasize the use of local anesthetic infiltration, nonsteroidal antiinflammatory drugs, acetaminophen, topical analgesics, surgical wound cooling, and when necessary, safer opioid medications, such as tramadol and intranasal butorphanol.

Variations in loop gain and arousal threshold during NREM sleep are affected by time of day over a 24-hour period in participants with obstructive sleep apnea.

We investigated whether time of day affects loop gain (LG) and the arousal threshold (AT) during non-rapid eye movement (NREM) sleep. Eleven men with obstructive sleep apnea (apnea-hypopnea index > 5 events/h) completed a constant-routine protocol that comprised 3-h sleep sessions in the evening [10 PM (1) to 1 AM], morning (6 AM to 9 AM), afternoon (2 PM to 5 PM), and subsequent evening [10 PM (2) to 1 AM]. During each sleep session LG and the AT were measured during NREM sleep with a model-based approach. Our results showed the presence of a rhythmicity in both LG (P < 0.0001) and the AT (P < 0.001) over a 24-h period. In addition, LG and the AT were greater in the morning compared with both evening sessions [6 AM vs. 10 PM (1) vs. 10 PM (2): LG (1 cycle/min): 0.71 ± 0.23 vs. 0.60 ± 0.22 (P = 0.01) vs. 0.56 ± 0.10 (P < 0.001), AT (fraction of eupneic breathing): 1.45 ± 0.47 vs. 1.28 ± 0.36 (P = 0.02) vs. 1.20 ± 0.18 (P = 0.001)]. No difference in LG and the AT existed between the evening sessions (LG: P = 0.27; AT: P = 0.24). LG was correlated to measures of the hypocapnic ventilatory response (i.e., a measure of chemoreflex sensitivity) (r = 0.72 and P = 0.045) and the critical closing pressure (i.e., a measure of airway collapsibility) (r = 0.77 and P = 0.02) that we previously published. We conclude that time of day, independent of hallmarks of sleep apnea, affects LG and the AT during NREM sleep. These modifications may contribute to increases in breathing instability in the morning compared with other periods throughout the day/night cycle in individuals with obstructive sleep apnea. In addition, efficaciousness of treatments for obstructive sleep apnea that target LG and the AT may be modified by a rhythmicity in these variables.NEW & NOTEWORTHY Loop gain and the arousal threshold during non-rapid eye movement (NREM) sleep are greater in the morning compared with the afternoon and evening. Loop gain measures are correlated to chemoreflex sensitivity and the critical closing pressure measured during NREM sleep in the evening, morning, and afternoon. Breathing (in)stability and efficaciousness of treatments for obstructive sleep apnea may be modulated by a circadian rhythmicity in loop gain and the arousal threshold.

Novel Changes in Resident Education during a Pandemic: Strategies and Approaches to Maximize Residency Education and Safety.

Introduction The COVID-19 pandemic has led to a reduction in surgical and clinical volume, which has altered the traditional training experience of the otolaryngology resident. Objective To describe the strategies we utilized to maximize resident education as well as ensure patient and staff safety during the pandemic. Methods We developed a system that emphasized three key elements. First and foremost, patient care remained the core priority. Next, clinical duties were restructured to avoid unnecessary exposure of residents. The third component was ensuring continuation of resident education and maximizing learning experiences. Results To implement these key elements, our residency divided up our five hospitals into three functional groups based on geographical location and clinical volume. Each team works for three days at their assigned location before being replaced by the next three-person team at our two busiest sites. Resident teams are kept completely separate from each other, so that they do not interact with those working at other sites. Conclusions Despite the daily challenges encountered as we navigate through the COVID-19 pandemic, our otolaryngology residency program has been able to establish a suitable balance between maintenance of resident safety and well-being without compromise to patient care.

The role of immune checkpoint inhibitors in anaplastic thyroid cancer (Case Series).

Anaplastic thyroid carcinoma (ATC) is a rare type of thyroid neoplasm. However, it is one of the most aggressive forms of malignancy accounting for approximately 50% of mortality associated with all thyroid cancers. Here we report two cases of ATC treated with immune checkpoint inhibitors. Next generation sequencing identified BRAFV600E mutation in one of the patients who also derived benefit from BRAF targeted therapy. We here discuss these cases highlighting the importance of expert pathological review, utilizing molecular testing to identify the underlying genetic targets for personalized therapy, and the potential role of PD-1 inhibitors for the treatment of ATC.

Perioperative Analgesia for Patients Undergoing Thyroidectomy and Parathyroidectomy: An Evidence-Based Review.

OBJECTIVE: To perform an evidence-based systematic review evaluating perioperative analgesia, including opioid alternatives, used for patients undergoing thyroidectomy and parathyroidectomy. METHODS: A comprehensive literature search from 1997 to January 2018 of Pubmed, Cochrane, and EmBase libraries was performed for studies reporting analgesic administration following thyroid or parathyroid surgery. This systematic review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Studies were evaluated for level of evidence and given a Jadad score to assess for risk of bias. Outcomes gathered included postoperative pain scores, time to rescue analgesia, rescue analgesic consumption, and adverse events. RESULTS: Thirty-eight randomized controlled trials met inclusion criteria. The GRADE criteria determined the overall evidence to be moderate-high. Studies utilizing NSAIDs reported reduced requirements for rescue analgesics. Acetaminophen studies presented with conflicting data on effectiveness. Gabapentinoid studies demonstrated lower pain scores and an increased time to rescue analgesic. Local anesthetics were effective at decreasing Visual Analogue Scale (VAS) and Numeric Rating Scale (NRS) pain scores while also reducing rescue analgesic consumption. Ketamine was shown to increased postoperative nausea and vomiting. NSAIDs and local anesthetic studies had an aggregate grade of evidence A, while all others had grade B evidence. CONCLUSION: There is significant evidence supporting the use of NSAIDs and local anesthetics in the perioperative period for pain management for thyroid and parathyroid surgeries. Acetaminophen, gabapentinoid and ketamine have some supporting evidence and may serve as adequate alternatives. Further multi-institutional RCTs are warranted to delineate optimal analgesic regimens. LEVEL OF EVIDENCE: NA.