Her Legacy Lives On: Celebrating the Women Behind Head and Neck Eponyms.

This article profiles 6 notable female scientists who have had eponyms named after them, highlighting their significant contributions to various medical fields and whose scientific endeavors have influenced our practice and understanding of otolaryngology. We discuss Lucja Frey Gottesman and her description of Frey's syndrome; Margaret Dix and the Dix-Hallpike test; Lotte Strauss and her work defining Churg-Strauss disease; Dorothy Reed Mendenhall's discovery of Reed-Sternberg cells in Hodgkin's lymphoma; Edith Louise Potter defining Potter sequence in utero; Denise Louis-Bar originally characterizing the condition now known as ataxia-telangiectasia or Louis-Bar syndrome. Despite the challenges these women faced as pioneering female physicians as well as personal and political turmoil, their contributions greatly advanced the fields of otolaryngology, neurology, neuropathology, perinatology, and pediatric pathology. We aim to honor their stories and medical legacies.

Differences in music appreciation between bilateral and single-sided cochlear implant recipients.

OBJECTIVE: To compare changes in music appreciation after cochlear implant (CI) surgery for patients with bilateral and single-sided deafness (SSD). METHODS: A retrospective cohort study was performed on all adult CI unilateral or bilateral recipients from November 2019 to March 2023. Musical questionnaire subset data from the Cochlear Implant Quality of Life (CIQOL) - 35 Profile Instrument Score (maximum raw score of 15) was collected. Functional CI assessment was measured with CI-alone speech-in-quiet (SIQ) scores (AzBio and CNC). RESULTS: 22 adults underwent CI surgery for SSD and 21 adults for bilateral deafness (8 sequentially implanted). Every patient group had clinically significant improvements (p < 0.001) in mean SIQ scores in the most recently implanted ear (Azbio (% correct) SSD: 14.23 to 68.48, bilateral: 24.54 to 82.23, sequential: 6.25 to 82.57). SSD adults on average had higher music QOL scores at baseline (SSD: 11.05; bilateral: 7.86, p < 0.001). No group had significant increases in raw score at the first post-operative visit (SSD: 11.45, p = 0.86; bilateral: 8.15, p = 0.15). By the most recent post-implantation evaluation (median 12.8 months for SSD, 12.3 months for bilateral), SSD adults had a significant increase in raw score from baseline (11.05 to 12.45, p = 0.03), whereas bilaterally deafened (7.86 to 9.38, p = 0.12) adults had nonsignificant increases. CONCLUSIONS: SSD patients demonstrate higher baseline music appreciation than bilaterally deafened individuals regardless of unilateral or bilateral implantation and are more likely to demonstrate continued improvement in subjective music appreciation at last follow-up even when speech perception outcomes are similar.

PHQ-9 and GAD-7 Score Response After Parathyroidectomy for Primary Hyperparathyroidism: a Systematic Review and Meta-analysis.

OBJECTIVE: Currently, the relationship between parathyroidectomy and objective neuropsychiatric outcomes are not clearly defined. The purpose of this study is to perform the first ever Meta-analysis of preoperative and postoperative PHQ-9 and GAD-7 scores in patients with primary hyperparathyroidism undergoing parathyroidectomy with the goal of identifying a specific psychometric score that could be used as an indication for surgical intervention. DATA SOURCES: A comprehensive search of the literature was performed using PubMed, Embase, PsycINFO, Web of Science, and Ovid All EBM Reviews. REVIEW METHODS: Studies met inclusion criteria if they evaluated preoperative and postoperative PHQ-9 and/or GAD-7 scores in patients with primary hyperparathyroidism undergoing parathyroidectomy. Random effects Meta-analyses were used to analyze the compiled data. RESULTS: The literature search returned 1433 articles for initial review of which 6 (1105 participants) met criteria for inclusion and Meta-analysis. Meta-analysis revealed that primary hyperparathyroidism patients had significantly higher presurgical PHQ-9 scores when compared to control groups. Additionally, patients experienced a statistically significant and sustained decrease in PHQ-9 scores following parathyroidectomy. Notably, there was a dramatic decrease in the percentage of patients with PHQ-9 scores ≥10 (considered clinically significant for depression) following parathyroidectomy. CONCLUSION: Patients with primary hyperparathyroidism experience a statistically significant and sustained improvement in PHQ-9 scores following parathyroidectomy. Additionally, symptoms of anxiety and suicidal ideation appear to decrease after parathyroidectomy. We propose that a PHQ-9 score ≥10 could potentially be used as an indication for parathyroidectomy in patients with asymptomatic primary hyperparathyroidism.

Influence of metabolic stress and metformin on synaptic protein profile in SH-SY5Y-derived neurons.

Insulin resistance (IR) is associated with reductions in neuronal proteins often observed with Alzheimer's disease (AD), however, the mechanisms through which IR promotes neurodegeneration/AD pathogenesis are poorly understood. Metformin (MET), a potent activator of the metabolic regulator AMPK is used to treat IR but its effectiveness for AD is unclear. We have previously shown that chronic AMPK activation impairs neurite growth and protein synthesis in SH-SY5Y neurons, however, AMPK activation in IR was not explored. Therefore, we examined the effects of MET-driven AMPK activation with and without IR. Retinoic acid-differentiated SH-SY5Y neurons were treated with: (1) Ctl: 24 h vehicle followed by 24 h Vehicle; (2) HI: 100 nM insulin (24 h HI followed by 24 h HI); or (3) MET: 24 h vehicle followed by 24 h 2 mM metformin; (4) HI/MET: 24 h 100 nM insulin followed by 24 h 100 nM INS+2 mM MET. INS and INS/MET groups saw impairments in markers of insulin signaling (Akt S473, mTOR S2448, p70s6k T389, and IRS-1S636) demonstrating IR was not recovered with MET treatment. All treatment groups showed reductions in neuronal markers (post-synaptic marker HOMER1 mRNA content and synapse marker synaptophysin protein content). INS and MET treatments showed a reduction in the content of the mature neuronal marker NeuN that was prevented by INS/MET. Similarly, increases in cell size/area, neurite length/area observed with INS and MET, were prevented with INS/MET. These findings indicate that IR and MET impair neuronal markers through distinct pathways and suggest that MET is ineffective in treating IR-driven impairments in neurons.

Eponyms in Otology: A Historical Narrative of Commonly Used Surgical Instruments.

Numerous eponymous instruments are regularly used in the otology surgical suite. This manuscript uses a tympanoplasty to highlight 10 frequently used instruments and the remarkable surgeons behind their creation. Many of these names will be familiar, but we hope our readers will gain an appreciation of these landmark figures that have transformed the practice of otology.

Acute interleukin-6 modulates key enzymes involved in prefrontal cortex and hippocampal amyloid precursor protein processing.

Exercise has been shown to be beneficial for individuals with Alzheimer's disease (AD). In rodent models of AD, exercise decreases the amyloidogenic processing of the amyloid precursor protein (APP). Although it remains unclear as to how exercise is promoting this shift away from pathological APP processing, there is emerging evidence that exercise-induced factors released from peripheral tissues may facilitate these alterations in brain APP processing. Interleukin-6 (IL-6) is released from multiple organs into peripheral circulation during exercise and is among the most characterized exerkines. The purpose of this study is to examine whether acute IL-6 can modulate key enzymes responsible for APP processing, namely, a disintegrin and metalloproteinase 10 (ADAM10) and ß-site amyloid precursor protein-cleaving enzyme 1 (BACE1), which initiate the nonamyloidogenic and amyloidogenic cascades, respectively. Male 10-wk-old C57BL/6J mice underwent acute treadmill exercise bout or were injected with either IL-6 or a PBS control 15 min prior to tissue collection. ADAM10 and BACE1 enzyme activity, mRNA, and protein expression, as well as downstream markers of both cascades, including soluble APPα (sAPPα) and soluble APPß (sAPPß), were examined. Exercise increased circulating IL-6 and brain IL-6 signaling (pSTAT3 and Socs3 mRNA). This occurred alongside a reduction in BACE1 activity and an increase in ADAM10 activity. IL-6 injection reduced BACE1 activity and increased sAPPα protein content in the prefrontal cortex. In the hippocampus, IL-6 injection decreased BACE1 activity and sAPPß protein content. Our results show that acute IL-6 injection increases markers of the nonamyloidogenic cascade and decreases markers of the amyloidogenic cascade in the cortex and hippocampus of the brain.NEW & NOTEWORTHY It is becoming evident that exercise modulates APP processing and can reduce amyloid-beta (Aß) peptide production. Our data help to explain this phenomenon by highlighting IL-6 as an exercise-induced factor that lowers pathological APP processing. These results also highlight brain regional differences in response to acute IL-6.

Ergonomics in Otolaryngology: A Systematic Review and Meta-analysis.

OBJECTIVES: To determine the proportion of otolaryngologists with work-related musculoskeletal discomfort (WRMD) and to review objective ergonomic data that contribute to WRMD. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A comprehensive search of the literature identified 1121 articles for initial review of which 19 (3563 participants) met criteria for qualitative discussion and eight (2192 participants) met criteria for meta-analysis. Random effects meta-analyses were used to estimate the proportion of otolaryngologists reporting WRMD. RESULTS: The overall proportion (95% confidence intervals [CI]) of general otolaryngologists reporting WRMD was 0.79 (0.66, 0.88) for any symptoms; 0.54 (0.40, 0.67) for neck symptoms; 0.33 (0.20, 0.49) for shoulder symptoms; and 0.49 (0.40, 0.59) for back symptoms. Surgeons performing primarily subspecialty cases had a lower estimated overall prevalence of WRMD versus those performing general ENT cases, however the odds ratio (OR) was not statistically significant (OR [95% confidence interval] 0.53 [0.22, 1.25]). 23%-84% of otolaryngologists underwent medical treatment for WRMD. 5%-23% took time off work and 1%-6% stopped operating completely as a result of WRMD. 23%-62.5% of otolaryngologists believed WRMD negatively impacted their quality of life. Objective measures of ergonomic posture indicate moderate to severe risk of injury during the routine clinic and surgical procedures with none found to be low risk. CONCLUSIONS: Ergonomic stressors among otolaryngologists contribute to a high rate of WRMD across all subspecialties with notable impact on productivity, longevity, and quality of life. Laryngoscope, 133:467-475, 2023.

Smoking and other patient factors in HPV-mediated oropharynx cancer: A retrospective cohort study.

PURPOSE: To characterize the significance of patient-level influences, including smoking history, on oncologic outcomes in human papillomavirus (HPV)-mediated oropharyngeal cancer (OPC). MATERIALS AND METHODS: A bi-institutional retrospective cohort study of previously untreated, HPV+ OPC patients who underwent curative treatment from 1/1/2008 to 7/1/2018 was performed. The primary outcome was disease-free survival (DFS) and the primary exposure was ≤10 versus >10-pack-year (PY)-smoking history. RESULTS: Among 953 OPC patients identified, 342 individuals with HPV+ OPC were included. The median patient age was 62 years, 33.0% had a > 10-PY-smoking history, 60.2% had AJCC8 stage I disease, and 35.0% underwent primary surgery. The median follow-up was 49 months (interquartile range [IQR] 32-75 months). Four-year DFS-estimates were similar among patients with ≤10-PY-smoking history (78.0%, 95% CI:71.7%-83.1%) compared to >10-PYs (74.8%; 95% CI:65.2%-82.0%; log-rank:p = 0.53). On univariate analysis, >10-PY-smoking history did not correlate with DFS (hazard ratio[HR]:1.15;95% CI:0.74-1.79) and remained nonsignificant when forced into the multivariable model. On adjusted analyses, stage, treatment paradigm, and age predicted DFS. Neither >10-PYs, nor any other definition of tobacco use (e.g., current smoker or > 20-PYs) was predictive of DFS, overall survival, or disease-specific survival. Conversely, age nonsignificantly and significantly predicted adjusted DFS (adjusted HR[aHR]:1.02,95% CI:0.997-1.05, p = 0.08), overall survival (aHR 1.05; 95% CI: 1.02-1.08; p = 0.002) and disease-specific survival (aHR 1.04;95% CI: 0.99-1.09;p = 0.09). CONCLUSION: Other than age, patient-level influences may not be primary drivers of HPV+ OPC outcomes. Although limited by its modest sample size, our study suggests the significance of smoking has been overstated in this disease. These findings and the emerging literature collectively do not support risk-stratification employing the >10-PY threshold. LEVEL OF EVIDENCE: Level 4.

Image-Guided Cochlear Implant Programming: A Systematic Review and Meta-analysis.

OBJECTIVE: To review studies evaluating clinically implemented image-guided cochlear implant programing (IGCIP) and to determine its effect on cochlear implant (CI) performance. DATA SOURCES: PubMed, EMBASE, and Google Scholar were searched for English language publications from inception to August 1, 2021. STUDY SELECTION: Included studies prospectively compared intraindividual CI performance between an image-guided experimental map and a patient's preferred traditional map. Non-English studies, cadaveric studies, and studies where imaging did not directly inform programming were excluded. DATA EXTRACTION: Seven studies were identified for review, and five reported comparable components of audiological testing and follow-up times appropriate for meta-analysis. Demographic, speech, spectral modulation, pitch accuracy, and quality-of-life survey data were collected. Aggregate data were used when individual data were unavailable. DATA SYNTHESIS: Audiological test outcomes were evaluated as standardized mean change (95% confidence interval) using random-effects meta-analysis with raw score standardization. Improvements in speech and quality-of-life measures using the IGCIP map demonstrated nominal effect sizes: consonant-nucleus-consonant words, 0.15 (-0.12 to 0.42); AzBio quiet, 0.09 (-0.05 to 0.22); AzBio +10 dB signal-noise ratio, 0.14 (-0.01 to 0.30); Bamford-Kowel-Bench sentence in noise, -0.11 (-0.35 to 0.12); Abbreviated Profile of Hearing Aid Benefit, -0.14 (-0.28 to 0.00); and Speech Spatial and Qualities of Hearing Scale, 0.13 (-0.02 to 0.28). Nevertheless, 79% of patients allowed to keep their IGCIP map opted for continued use after the investigational period. CONCLUSION: IGCIP has potential to precisely guide CI programming. Nominal effect sizes for objective outcome measures fail to reflect subjective benefits fully given discordance with the percentage of patients who prefer to maintain their IGCIP map.

Chronic AMPK Activation Reduces the Expression and Alters Distribution of Synaptic Proteins in Neuronal SH-SY5Y Cells.

Neuronal growth and synaptic function are dependent on precise protein production and turnover at the synapse. AMPK-activated protein kinase (AMPK) represents a metabolic node involved in energy sensing and in regulating synaptic protein homeostasis. However, there is ambiguity surrounding the role of AMPK in regulating neuronal growth and health. This study examined the effect of chronic AMPK activation on markers of synaptic function and growth. Retinoic-acid-differentiated SH-SY5Y human neuroblastoma cells were treated with A-769662 (100 nM) or Compound C (30 nM) for 1, 3, or 5 days before AMPK, mTORC1, and markers for synapse function were examined. Cell morphology, neuronal marker content, and location were quantified after 5 days of treatment. AMPK phosphorylation was maintained throughout all 5 days of treatment with A-769662 and resulted in chronic mTORC1 inhibition. Lower total, soma, and neuritic neuronal marker contents were observed following 5 d of AMPK activation. Neurite protein abundance and distribution was lower following 5 days of A-769662 treatment. Our data suggest that chronic AMPK activation impacts synaptic protein content and reduces neurite protein abundance and distribution. These results highlight a distinct role that metabolism plays on markers of synapse health and function.

Characteristics and outcomes of young patients with laryngeal cancer: National hospital-based retrospective cohort analysis.

BACKGROUND: The relative incidence of laryngeal cancer is rising in young patients, yet their characteristics, risk factors, and outcomes relative to older patients are poorly understood. METHODS: Retrospective cohort analysis of the National Cancer Database from 2006 to 2015. RESULTS: Among 25 029 total patients, 923 (3.7%) were young (<45 years old) and 3266 underwent tumor HPV testing. Compared to older patients, a greater proportion of young patients were female (30.3%, 23.3%; p < 0.001) and seen with high-risk HPV-positive tumors (29.9%, 12.4%; p < 0.001). In subset analyses of young patients, females with higher income (≥$38 000) exhibited a decreased risk of overall mortality compared to all other sex-income subcategories (adjusted hazard ratio [aHR]: 0.43, 95% confidence interval [CI]: 0.25-0.72). In subset analyses of patients of all ages with known tumor HPV status, patients with high-risk HPV-positive tumors exhibited a reduced risk of all-cause mortality (aHR: 0.74, 95%CI: 0.60-0.92, p = 0.007). CONCLUSION: The interdependent associations between age, sex, tumor HPV status, and income on laryngeal cancer outcomes warrant further investigation.

Lesser Known Uses of γ-Aminobutyric Acid Analogue Medications in Otolaryngology.

OBJECTIVES/HYPOTHESIS: In otolaryngology, γ-aminobutyric acid (GABA) analogues have been previously analyzed for their roles in neuropathic pain, chronic cough, tinnitus, and perioperative analgesia. The primary aim of this study is to comprehensively summarize and synthesize the existing evidence for lesser known uses of gabapentin and pregabalin in otolaryngology. STUDY DESIGN: A scoping review conducted of the available English-language literature was performed by two authors through April 1, 2021. METHODS: The Preferred Reporting Items for Systematic Review and Meta-Analysis criteria were followed, and a quality assessment of included studies was performed using the Methodological Index for Non-Randomized Studies. RESULTS: Ten studies met inclusion criteria. Three studies found that gabapentin may reduce gastrostomy tube usage and improve swallowing function in head and neck cancer patients undergoing radiation therapy (RT). Three studies suggested that gabapentin may help reduce opiate use when used as a primary analgesic in patients with radiation-induced mucositis. One study demonstrated that pregabalin-reduced trismus severity in patients with radiotherapy-induced trismus. One study demonstrated gabapentin may be useful in patients with phonasthenia. Two studies demonstrated that GABA analogues may be a useful adjunct in patients with globus pharyngeus in the context of likely laryngeal sensory neuropathy. CONCLUSIONS: The most promising potential uses for GABA analogues identified in this review are for improving swallowing, trismus, and narcotic overuse after RT. The benefit of GABA analogues for improving nonorganic voice disorders is also promising while the benefit for globus pharyngeus when possibly related to laryngeal sensory neuropathy is inconclusive. Laryngoscope, 132:954-964, 2022.

The cell phone vibration test: A telemedicine substitute for the tuning fork test.

OBJECTIVE: An at home-test for differentiating between conductive and sensorineural hearing loss remains elusive. Our goal was to validate the novel cell-phone vibration test (CPVT) against the Weber tuning fork test (WTFT) and to assess if the CPVT can be self-administered by patients reliably. STUDY DESIGN: Cross-sectional. METHODS: The CPVT involves placement of a vibrating cellphone on the center of the forehead to determine which ear perceives the sound louder. 40 consecutive adult patients with an audiogram within 6 months and no report of recent hearing changes were recruited. Group 1 consisted of 20 patients who were examined by the provider with the CPVT and WTFT using various tuning forks (256, 512, and 1024 Hz). Group 2 consisted of an additional 20 patients who received instructions on self-administering the CPVT. Kappa statistics were calculated to assess the strength of concordance between the CPVT, WTFT, and audiometric findings for group 1 and between patient self-administered and provider administered CPVT and WTFT for group 2. RESULTS: Concordance between CPVT and WTFT in the entire cohort was substantial (Kappa coefficient: 0.81 for 256 Hz, 0.73 for 512 Hz, and 0.62 for 1024 Hz) with similar concordances between actual and expected results based on audiogram (Kappa coefficient: 0.52 for CPVT and 0.52 for WTFT). Concordance between patient-administered and provider-administered CPVT showed almost perfect agreement (Kappa coefficient: 0.92). CONCLUSIONS: The CPVT provides consistent results when compared to a formal WTFT and can be reliably self-administered by patients with appropriate instructions.Level of evidence: 4.

Sex-Specific Effects of Plastic Caging in Murine Viral Myocarditis.

BACKGROUND: Myocarditis is an inflammatory heart disease caused by viral infections that can lead to heart failure, and occurs more often in men than women. Since animal studies have shown that myocarditis is influenced by sex hormones, we hypothesized that endocrine disruptors, which interfere with natural hormones, may play a role in the progression of the disease. The human population is exposed to the endocrine disruptor bisphenol A (BPA) from plastics, such as water bottles and plastic food containers. METHODS: Male and female adult BALB/c mice were housed in plastic versus glass caging, or exposed to BPA in drinking water versus control water. Myocarditis was induced with coxsackievirus B3 on day 0, and the endpoints were assessed on day 10 post infection. RESULTS: We found that male BALB/c mice that were exposed to plastic caging had increased myocarditis due to complement activation and elevated numbers of macrophages and neutrophils, whereas females had elevated mast cell activation and fibrosis. CONCLUSIONS: These findings show that housing mice in traditional plastic caging increases viral myocarditis in males and females, but using sex-specific immune mechanisms.

Extracapsular extension, pathologic node status, and adjuvant treatment in primary surgery patients with human papillomavirus-mediated oropharyngeal cancer: National hospital-based retrospective cohort analysis.

BACKGROUND: The significance of extracapsular extension (ECE) and adjuvant treatment paradigm in patients with surgically managed human papillomavirus-positive (HPV+) oropharyngeal cancer (OPC) is debated. METHODS: National, hospital-based, retrospective cohort study of 2663 patients pN+ HPV+ OPC who underwent primary surgery. RESULTS: Patients with ECE had a 1.74-times risk of death (95% confidence interval [CI]: 1.26-2.40, p = 0.001) compared to patients without ECE. Among patients with pN1, ECE-positive disease, risk of overall mortality was similar across treatment paradigms (surgery alone: ref; adjuvant radiation therapy [RT]: aHR: 0.81; 95% CI: 0.36-1.85; p = 0.62; adjuvant CRT: aHR: 0.66; 95% CI: 0.34-1.32; p = 0.24). Patients with pN2 ECE-positive disease treated with adjuvant RT alone exhibited similar risk of all-cause mortality (hazard ratio: 1.04, 95% CI: 0.24-4.47, p = 0.96) compared to adjuvant chemoradiation (CRT). In patients with advanced, ECE-positive disease (e.g., pT3-T4pN2), adjuvant CRT did not reduce the risk of overall mortality relative to adjuvant RT. CONCLUSION: Although pathologic ECE negatively predicts for survival in patients with HPV+ OPC, our analyses support expansion of postoperative de-intensification clinical trial eligibility criteria in patients with ECE-positive disease.

Addition of Metformin to Concurrent Chemoradiation in Patients With Locally Advanced Non-Small Cell Lung Cancer: The NRG-LU001 Phase 2 Randomized Clinical Trial.

IMPORTANCE: Non-small cell lung cancer (NSCLC) has relatively poor outcomes. Metformin has significant data supporting its use as an antineoplastic agent. OBJECTIVE: To compare chemoradiation alone vs chemoradiation and metformin in stage III NSCLC. DESIGN, SETTING, AND PARTICIPANTS: The NRG-LU001 randomized clinical trial was an open-label, phase 2 study conducted from August 24, 2014, to December 15, 2016. Patients without diabetes who were diagnosed with unresectable stage III NSCLC were stratified by performance status, histology, and stage. The setting was international and multi-institutional. This study examined prespecified endpoints, and data were analyzed on an intent-to-treat basis. Data were analyzed from February 25, 2019, to March 6, 2020. INTERVENTIONS: Chemoradiation and consolidation chemotherapy with or without metformin. MAIN OUTCOMES AND MEASURES: The primary outcome was 1-year progression-free survival (PFS), designed to detect 15% improvement in 1-year PFS from 50% to 65% (hazard ratio [HR], 0.622). Secondary end points included overall survival, time to local-regional recurrence, time to distant metastasis, and toxicity per Common Terminology Criteria for Adverse Events, version 4.03. RESULTS: A total of 170 patients were enrolled, with 167 eligible patients analyzed after exclusions (median age, 64 years [interquartile range, 58-72 years]; 97 men [58.1%]; 137 White patients [82.0%]), with 81 in the control group and 86 in the metformin group. Median follow-up was 27.7 months (range, 0.03-47.21 months) among living patients. One-year PFS rates were 60.4% (95% CI, 48.5%-70.4%) in the control group and 51.3% (95% CI, 39.8%-61.7%) in the metformin group (HR, 1.15; 95% CI, 0.77-1.73; P = .24). Clinical stage was the only factor significantly associated with PFS on multivariable analysis (HR, 1.79; 95% CI, 1.19-2.69; P = .005). One-year overall survival was 80.2% (95% CI, 69.3%-87.6%) in the control group and 80.8% (95% CI, 70.2%-87.9%) in the metformin group. There were no significant differences in local-regional recurrence or distant metastasis at 1 or 2 years. No significant difference in adverse events was observed between treatment groups. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the addition of metformin to concurrent chemoradiation was well tolerated but did not improve survival among patients with unresectable stage III NSCLC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02186847.

Comparing the clinical outcomes across different sodium/glucose cotransporter 2 (SGLT2) inhibitors in heart failure patients: a systematic review and network meta-analysis of randomized controlled trials.

PURPOSE: Empagliflozin, dapagliflozin, canagliflozin, and ertugliflozin have been shown in randomized controlled trials to improve cardiovascular, metabolic, and renal outcomes in heart failure patients. To date, there has not been any meta-analysis examining the differences in clinical outcomes across different SGLT2 inhibitors in heart failure patients. METHODS: Four electronic databases (PubMed, Embase, Cochrane, SCOPUS) were searched on 13 September 2020 for articles published from 1 January 2000 to 13 September 2020 examining the effect of SGLT2 inhibitors on cardiovascular, renal, and metabolic outcomes in heart failure patients. Frequentist network meta-analysis was performed on extracted data. RESULTS: Ten randomized controlled trials were included with a combined cohort of 15,373 patients. In heart failure patients, frequentist network meta-analysis demonstrated no demonstrable difference in treatment effect across the SGLT2 inhibitors for heart failure hospitalization, cardiovascular deaths, composite of cardiovascular deaths and heart failure hospitalizations, all-cause mortality, and a composite of cardiovascular deaths and non-fatal myocardial infarction and non-fatal stroke. There was no demonstrable difference in treatment effect for worsening renal function or the weighted mean difference for weight, hemoglobin A1c, and systolic blood pressure. CONCLUSIONS: There were no demonstrable treatment differences across SGLT2 inhibitors across cardiovascular, renal, and metabolic outcomes, although this needs to be interpreted considering the wide confidence intervals, limited number of included studies, and heterogeneity present. Future research of different SGLT2 inhibitors in head-to-head studies is warranted to determine if there is a drug class effect.

Resveratrol, Metabolic Dysregulation, and Alzheimer's Disease: Considerations for Neurogenerative Disease.

Alzheimer's disease (AD) has traditionally been discussed as a disease where serious cognitive decline is a result of Aß-plaque accumulation, tau tangle formation, and neurodegeneration. Recently, it has been shown that metabolic dysregulation observed with insulin resistance and type-2 diabetes actively contributes to the progression of AD. One of the pathologies linking metabolic disease to AD is the release of inflammatory cytokines that contribute to the development of brain neuroinflammation and mitochondrial dysfunction, ultimately resulting in amyloid-beta peptide production and accumulation. Improving these metabolic impairments has been shown to be effective at reducing AD progression and improving cognitive function. The polyphenol resveratrol (RSV) improves peripheral metabolic disorders and may provide similar benefits centrally in the brain. RSV reduces inflammatory cytokine release, improves mitochondrial energetic function, and improves Aß-peptide clearance by activating SIRT1 and AMPK. RSV has also been linked to improved cognitive function; however, the mechanisms of action are less defined. However, there is evidence to suggest that chronic RSV-driven AMPK activation may be detrimental to synaptic function and growth, which would directly impact cognition. This review will discuss the benefits and adverse effects of RSV on the brain, highlighting the major signaling pathways and some of the gaps surrounding the use of RSV as a treatment for AD.

Gender and authorship trends in rhinology, allergy, and skull-base literature from 2008 to 2018.

BACKGROUND: A recent analysis suggested potential narrowing of the gender gap in research productivity in the field of rhinology. This analysis did not, however, provide insight into how the genders are represented in the rhinologic literature. This study aimed to evaluate 11 years of literature to evaluate for gender differences in authorship position, collaborations, category and content of research, citations, and funding to gain perspective on how gender and authorship has changed over time. METHODS: Authorship data for all articles on rhinologic subject matter published between January 1, 2008 and December 31, 2018 in four otolaryngology journals was collected. The gender of authors was determined by protocol. Category and content of research and funding status/source were additionally obtained. RESULTS: Data were collected from 2666 articles. Gender of 14,510 authors was determined. Female authors accounted for 23% of the overall authors and male authors accounted for 77%. Female first authorship increased significantly over time, but there was no change in female senior authorship. The percentage of female authors steadily increased over time, whereas male authorship decreased slightly. Mixed gender teams were shown to be increasing in frequency. Women published more than expected in basic science and allergy and less than expected in skull base. On funded studies, women were significantly underrepresented as senior authors. CONCLUSION: This study represents the first assessment of gender differences in the rhinology literature. Areas where female representation can improve include senior authorship, increased involvement in skull base publications, and increased funding.