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There has been a disproportionate increase in the incidence of young patients with squamous cell carcinoma of the oral tongue (SCCOT). The purpose of this study was to compare young patients to older patients with SCCOT without prior drinking or smoking history as this population is poorly characterized in the literature.A retrospective review of patients presenting to our institution with SCCOT was performed. The clinical and pathologic characteristics, as well as, outcomes were compared between younger patients (age ≤45) and older patients (age45). Outcome analysis was performed using Kaplan Meier method. Multivariable Cox proportional hazard models were performed for age and stage.Eighty-two patients (38 young, 44 old) were included in this study. Median follow-up was 29.4 months. When compared to the older cohort (age45), the younger cohort (age ≤45) demonstrated lower rates of 5-year locoregional control (LC) (79.6% vs. 52.5%, p = 0.043) and distant metastasis-free survival (88.1% vs. 61.8%, p = 0.006). Both cohorts demonstrated similar overall survival rates (55.5% vs. 58.1%) and disease-specific survival (66.2% vs. 58.1%). Of patients experiencing locoregional failure with available radiation therapy plans and PET scans in younger cohorts (n = 7), 100% demonstrated in-field failures. Multivariable Cox proportional hazards demonstrated age was an independent predictor of DMFS (p = 0.004) and the advanced stage was a predictor of DSS (p = 0.03).Young, nondrinker, nonsmokers with SCCOT demonstrate high rates of locoregional recurrence, distant metastasis, and in-field failures. Future studies are warranted to determine underlying mechanisms driving pathogenesis in this unique cohort.3 Laryngoscope, 2022.

AMPA-type glutamate receptors (AMPARs) and major histocompatibility complex class I (MHC-I) proteins regulate synaptic signalling. Here we describe the importance of the cytoplasmic tail of MHC-I for its role in the central nervous system (CNS) in synaptic signalling and the modulation of synaptic glutamate receptor expression. We demonstrate that Y321F mutation of the conserved cytoplasmic tyrosine in MHC-I affects expression of the AMPAR, GluA2/3, and alters phosphorylation of a number of kinases, including Fyn, Lyn, p38, ERK1/2, JNK1/2/3, and p70 S6 kinase. These data elucidate the important role of MHC-1 on AMPAR function and modifications to the cytoplasmic tail of MHC-1 can alter synaptic strength, plasticity and learning and memory.

Major histocompatibility complex class I (MHC-I) proteins are expressed in neurons, where they regulate synaptic plasticity. However, the mechanisms by which MHC-I functions in the CNS remains unknown. Here we describe the first structural analysis of MHC-I, to resolve underlying mechanisms that explains its function. We demonstrate that Y321F mutation of the conserved cytoplasmic tyrosine-based endocytosis motif YXXΦ in MHC-I affects spine density and synaptic structure without affecting neuronal complexity. Furthermore, the impact of the Y321F substitution phenocopies the MHC-I null animals, demonstrating that reverse, outside-in signalling events sensing the external environment is the major mechanism that conveys this information to the neuron and this has an essential role in the regulation of synaptic plasticity.

Few treatments have demonstrated mortality benefits among hospitalized hypoxic COVID-19 patients. We evaluated the use of hyperbaric oxygen (HBO2) therapy as a therapeutic intervention among hospitalized patients with a high oxygen requirement prior to vaccine approval.We extracted data on patients with COVID-19 hypoxia who required oxygen supplementation ranging from a 6L nasal cannula up to a high-flow nasal cannula at 100% FiO2 at 60L/minute with a 100% non-rebreather mask at 15 L/minute and were eligible for off-label HBO2 therapy from October 2020 to February 2021. We followed the Monitored Emergency use of Unregistered and Investigational Interventions or (MEURI) in conjunction with the consistent re-evaluation of the protocol using the Plan-Do-Study-Act (PDSA) tool [1]. We compared patient characteristics and used Fisher's exact test and a survival analysis to assess the primary endpoint of inpatient death.HBO2 therapy was offered to 36 patients, of which 24 received treatment and 12 did not receive treatment. Patients who did not receive treatment were significantly older (p ≺ 0.01) and had worse baseline hypoxia (p = 0.06). Three of the 24 (13%) patients who received treatment died compared to six of 12 (50%) patients who did not receive treatment (RR ratio: 0.25, p = 0.04, 95% CI: 0.08 to 0.83). In the survival analysis, there was a statistically significant reduction in inpatient mortality in the treatment group (HR: 0.19, p = 0.02, 95% CI: 0.05-0.74). However, after adjusting for age and baseline hypoxia, there was no difference in inpatient mortality (hazard ratio: 0.48, p = 0.42, 95% CI: 0.08-2.86).The survival benefit of HBO2 therapy observed in our unadjusted analysis suggests that there may be therapeutic benefits of HBO2 in treating COVID-19 hypoxia as an adjunct to standard care.

ImportanceThe number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and these patients are underrepresented in clinical trials. It is unclear whether the addition of chemotherapy or cetuximab to radiotherapy is associated with improved survival in older adults with HNSCC.ObjectiveTo examine whether the addition of chemotherapy or cetuximab to definitive radiotherapy is associated with improved survival in patients with locoregionally advanced (LA) HNSCC.Design, Setting, and ParticipantsThe Special Care Patterns for Elderly HNSCC Patients Undergoing Radiotherapy (SENIOR) study is an international, multicenter cohort study including older adults (≥65 years) with LA-HNSCCs of the oral cavity, oropharynx/hypopharynx, or larynx treated with definitive radiotherapy, either alone or with concomitant systemic treatment, between January 2005 and December 2019 at 12 academic centers in the US and Europe. Data analysis was conducted from June 4 to August 10, 2022.InterventionsAll patients underwent definitive radiotherapy alone or with concomitant systemic treatment.Main Outcomes and MeasuresThe primary outcome was overall survival. Secondary outcomes included progression-free survival and locoregional failure rate.ResultsAmong the 1044 patients (734 men [70.3%]; median [IQR] age, 73 [69-78] years) included in this study, 234 patients (22.4%) were treated with radiotherapy alone and 810 patients (77.6%) received concomitant systemic treatment with chemotherapy (677 [64.8%]) or cetuximab (133 [12.7%]). Using inverse probability weighting to attribute for selection bias, chemoradiation was associated with longer overall survival than radiotherapy alone (hazard ratio [HR], 0.61; 95% CI, 0.48-0.77; P P = .70). Progression-free survival was also longer after the addition of chemotherapy (HR, 0.65; 95% CI, 0.52-0.81; P P = .19). The survival benefit of the chemoradiation group was present in patients up to age 80 years (65-69 years: HR, 0.52; 95% CI, 0.33-0.82; 70-79 years: HR, 0.60; 95% CI, 0.43-0.85), but was absent in patients aged 80 years or older (HR, 0.89; 95% CI, 0.56-1.41).Conclusions and RelevanceIn this cohort study of older adults with LA- HNSCC, chemoradiation, but not cetuximab-based bioradiotherapy, was associated with longer survival compared with radiotherapy alone.

Introduction: Few treatments have demonstrated mortality benefit among hospitalized hypoxic COVID-19 patients except for steroids. We evaluated the use of hyperbaric oxygen therapy (HBOT) as a therapeutic intervention among hospitalized patients with a high oxygen requirement.Methods: We extracted data on patients with COVID-19 hypoxia who required at least 6 L/min oxygen supplementation, and were eligible for off-label HBOT from October 2020 to February 2021. We compared patient characteristics and used Fisher’s exact test and a survival analysis to assess the primary endpoint of inpatient death.Results: We offered HBOT to 36 patients, of which 24 received treatment and 12 did not receive treatment. Patients who did not receive treatment were significantly older (P < 0.01) and had worse baseline hypoxia (P = 0.06). Three of the 24 (13%) patients who received treatment died compared to 6 of 12 (50%) patients who did not receive treatment (RR ratio: 0.25, P = 0.04, 95% CI: 0.08 to 0.83). In the survival analysis, there was a statistically significant reduction in inpatient mortality in the treatment group (HR: 0.19, P = 0.02, 95% CI: 0.05-0.74). However, after adjusting for age and baseline hypoxia, there was no difference in inpatient mortality (hazard ratio: 0.48, P = 0.42, 95% CI: 0.08-2.86).Conclusions: The survival benefit of HBOT observed in our unadjusted analysis suggests the need to further study therapeutic benefits of HBOT in treating COVID-19 hypoxia through randomized clinical trials.

Thirty percent of patients with head and neck squamous cell carcinoma (HNSCC) are at least 70 years of age. This number continues to rise as life expectancy continues to increase. Still, older adults with HNSCC remain underrepresented in clinical trials, resulting in ambiguity on optimal management. Older adults are a complex patient population, often requiring increased support due to issues relating to functional and performance status, medical comorbidities, and medication management. Furthermore, in older adults with HNSCC, many of these conditions are independently associated with increased toxicity and worse outcomes. Toxicity in the older adult remains difficult to predict and to understand, and as treatment decisions are based on treatment tolerability, it is essential to understand the toxicities and how to minimize them. Novel predictive scores are being developed specifically for older adults with HNSCC to understand toxicity and to assist in personalized treatment decisions. There are clinical trials presently underway that are investigating shortened radiation courses and novel, less toxic systemic treatments in this population. In the forthcoming sections, we provide a detailed overview of the clinical data, treatment paradigms, and considerations in this population. This review provides a comprehensive overview of existing clinical data and clinical considerations in the older adult head and neck cancer population. Additionally, we provide a detailed overview of pertinent current and ongoing clinical trials, as well as future areas for investigation.

Through the study of substituted anilines and benzylamines, we demonstrated that cooperative cation-π, π-π, and van der Waals interactions can increase aromatic cationic amine sorption to Na/Ca-montmorillonite well beyond the extent expected by cation exchange alone. Cationic amines exhibiting cooperative interactions displayed nonlinear S-shaped isotherms and increased affinity for the sorbent at low surface coverage; parallel cation exchange and cooperative interactions were noted above a sorption threshold of 0.3-2.3% of exchange sites occupied. Our experiments revealed the predominance of intermolecular cation-π interactions, which occurred between the π system of a compound retained on the surface via cation exchange and the cationic amine group of an adjacent molecule. Compounds with greater amine charge/area and electron-donating substituents that allowed for greater electron density at the center of the aromatic ring showed a greater potential for cation-π interactions on montmorillonite surfaces. However, benzylamine sorption to nine soils, at charge loadings comparable to the experiments with montmorillonite, revealed no significant cooperative interactions. It appears that cation-π interactions may be likely in soils with exceptionally high cation exchange capacities (0.7 mol charge/kg) and low organic matter contents, abundant in montmorillonite and other expanding clay minerals.