Loss of TDP-43 in astrocytes leads to motor deficits by triggering A1-like reactive phenotype and triglial dysfunction.

Patients with amyotrophic lateral sclerosis (ALS) can have abnormal TDP-43 aggregates in the nucleus and cytosol of their surviving neurons and glia. Although accumulating evidence indicates that astroglial dysfunction contributes to motor neuron degeneration in ALS, the normal function of TDP-43 in astrocytes are largely unknown, and the role of astroglial TDP-43 loss to ALS pathobiology remains to be clarified. Herein, we show that TDP-43-deleted astrocytes exhibit a cell-autonomous increase in GFAP immunoreactivity without affecting astrocyte or microglia proliferation. At the transcriptomic level, TDP-43-deleted astrocytes resemble A1-reactive astrocytes and induce microglia to increase C1q expression. These astrocytic changes do not cause loss of motor neurons in the spinal cord or denervation at the neuromuscular junction. In contrast, there is a selective reduction of mature oligodendrocytes, but not oligodendrocyte precursor cells, suggesting triglial dysfunction mediated by TDP-43 loss in astrocytes. Moreover, mice with astroglial TDP-43 deletion develop motor, but not sensory, deficits. Taken together, our results demonstrate that TDP-43 is required to maintain the protective functions of astrocytes relevant to the development of motor deficits in mice.

Low-FODMAP Diet for Irritable Bowel Syndrome: What We Know and What We Have Yet to Learn.

Irritable bowel syndrome (IBS) is the most prevalent of gastrointestinal (GI) conditions, affecting millions of people worldwide. Given that most IBS patients associate their GI symptoms with eating food, specific dietary manipulation has become an attractive treatment strategy. A diet low in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) has generated the greatest level of scientific and clinical interest. Overall, 52-86% of patients report significant improvement of their IBS symptoms with elimination of dietary FODMAPs. Patients who experience symptom improvement with FODMAP elimination should undergo a structured reintroduction of foods containing individual FODMAPs to determine sensitivities and allow for personalization of the diet plan. This review discusses the literature surrounding the administration of the low-FODMAP diet and its efficacy in the treatment of IBS.

A pilot study comparing the pharmacokinetics of injectable cyanocobalamin and hydroxocobalamin associated with a trace mineral injection in cattle.

Injectable vitamin B12 (cobalamin) is traditionally used to prevent or treat vitamin B12 deficiencies in ruminants. Sheep and human studies have demonstrated the superiority of a single dose of hydroxocobalamin (OHB12) over cyanocobalamin (CNB12) in maintaining high levels of cobalamin in plasma and liver. However, limited data are available for cattle. The purpose of this study was to compare the pharmacokinetics of two forms of cobalamin-OHB12 and CNB12-as a single subcutaneous injection of 28 µg/kg BW at the same time of a trace mineral injection in six non-cobalt/B12 -deficient Holstein-Friesian steers. Plasma and liver samples were obtained to determine cobalamin concentration after treatment. Cyanocobalamin had lower retention in plasma and liver than OHB12 (p < .05). Cobalamin levels peaked in plasma by 8 h after treatment in both groups. However, OHB12 reached a higher peak compared to CNB12. Levels of cobalamin in plasma dropped closer to baseline levels 24 h after CNB12 treatment while OHB12 maintained higher concentrations. Hydroxocobalamin increased significantly hepatic concentration of cobalamin 28 days after treatment, while CNB12 did not increase liver levels relative to pre-treatment (p < .05). These results confirm that a single subcutaneous OHB12 injection increases the level of cobalamin in the blood in the first 24 hours, and this increase is maintained in the liver for at least 28 days.

Cervical Esophageal Cancers: Challenges and Opportunities.

PURPOSE OF THE REVIEW: Cervical esophageal cancers (CECs) are a rare subset of esophageal cancers that are distinct in their management and outcomes. This review explores current data on the optimal management of this disease. RECENT FINDINGS: While outcomes for CEC have been suboptimal, several strategies have been proven beneficial in recent years. These include selective surgical resection or salvage surgery, chemoradiation (CRT) vs. radiation (RT) alone, dose escalation, IMRT, and induction chemotherapy. The optimal management of CEC to achieve the best oncological outcomes and minimize morbidity appears to be definitive chemoradiation with surgery reserved for selective salvage. While the benefit of dose escalated vs. standard dosing for radiation is unclear, most appear to use doses in excess of 50.4 Gy, even in the United States. IMRT might provide a benefit independent of allowing for dose escalation. Induction chemotherapy might allow for "chemoselection", but the benefit is unclear.

Factors Predictive of Receiving Adjuvant Radiotherapy in High-Intermediate-Risk Stage I Endometrial Cancer.

OBJECTIVES: Randomized trials have shown a local control benefit with adjuvant radiotherapy (RT) in high-intermediate-risk endometrial cancer patients, although not all such patients receive RT. We reviewed the National Cancer Data Base to investigate which patient/tumor-related factors are associated with delivery of adjuvant RT. METHODS: The National Cancer Data Base was queried for patients diagnosed with International Federation of Gynecology and Obstetrics 2009 stage I endometrioid adenocarcinoma from 1998 to 2012 who underwent surgery +/- adjuvant RT. Exclusion criteria were unknown stage/grade, nonsurgical primary therapy, less than 30 days' follow-up, RT of more than 6 months after surgery, or palliative treatment. High-intermediate risk was defined based on Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria: older than 60 years with stage IA grade 3 or stage IB grade 1-2. RESULTS: Seventeen thousand five hundred twenty-four met inclusion criteria, and the 13,651 patients with complete data were subjected to a multiple logistic regression analysis; 7814 (57.2%) received surgery alone, and 5837 (42.8%) received surgery + RT. Receipt of adjuvant RT was more likely among black women and women with higher income, Northeastern residence, diagnosis after 2010, greater than 50% myometrial invasion, and receipt of adjuvant chemotherapy (P < 0.05). Patients older than 80 years or those undergoing lymph node dissection were less likely to receive adjuvant RT (P < 0.05). Of those treated with RT, 44.0% received external beam therapy, 54.8% received vaginal cuff brachytherapy, and 0.6% received both. Among irradiated women, patients older than 80 years and those with Northeastern residence, treatment at academic facilities, diagnosis after 2004, and lymph node dissection were more likely to undergo brachytherapy over external beam radiation therapy (P < 0.05). Overall use of adjuvant RT was 28.8% between 1998 and 2004, 42.0% between 2005 and 2010, and 43.4% between 2011 and 2012; the difference between 1998-2004 and 2005-2010 was not statistically significant. CONCLUSIONS: Fewer than half of patients with high-intermediate-risk endometrial cancer by Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria received adjuvant RT despite evidence demonstrating improved local control. Both patient- and tumor-related factors are associated with delivery of adjuvant RT and the modality selected.

Adjuvant radiation therapy is associated with improved overall survival in high-intermediate risk stage I endometrial cancer: A national cancer data base analysis.

PURPOSE: Adjuvant radiation therapy (RT) was shown to improve local control in patients with high-intermediate risk (HIR) stage I endometrial cancer (EC) in randomized trials. Overall survival (OS) was not significantly different with adjuvant RT in these trials or subsequent meta-analyses; however, they were underpowered to assess OS. We used the National Cancer Data Base (NCDB) to examine the impact of adjuvant RT on OS in HIR EC patients. METHODS: The NCDB was queried for patients diagnosed with FIGO (2009) Stage I endometrioid adenocarcinoma from 1998 to 2012 who underwent surgery±adjuvant RT. Per ASTRO guidelines, HIR risk was defined as stage IB and/or grade 3. Patients were excluded if: non-surgical primary therapy, RT>180days after surgery, unknown stage/grade/RT status, or RT to targets outside pelvis/vagina. Kaplan-Meier plots and Cox proportional hazards regression were used. RESULTS: 33,600 patients met criteria. 18,070 patients (53.8%) received surgery alone, 15,530 patients (46.2%) received surgery+adjuvant RT. Of patients who received adjuvant RT, 42.2% received external beam RT, 44.7% brachytherapy, and 13.1% received both. 5-year OS was 79.2% for the surgery alone group and 83.3% for the surgery+adjuvant RT (p<0.0001). On multivariate analysis, adjuvant RT was independently associated with improved OS vs. surgery alone (HR 0.7; 95% CI 0.8-0.9, p<0.0001). CONCLUSIONS: Our results show that surgery+adjuvant RT was associated with a statistically significant 4.1% improvement in 5-year OS vs. surgery alone in stage I HIR EC. This data along suggests that the improvement in local control with adjuvant RT leads to improved OS.

Survival Differences Among Uterine Papillary Serous, Clear Cell and Grade 3 Endometrioid Adenocarcinoma Endometrial Cancers: A National Cancer Database Analysis.

OBJECTIVES: High-risk histology including UPSC, CC, and high-grade (G3) endometrioid adenocarcinoma (EAC) have a worse prognosis compared to G1-2 EAC. It is unknown whether G3EAC outcomes are more similar to UPSC/CC or to G1-2 EAC. The purpose of this study was to compare overall survival (OS) among UPSC, CC, and G1-3 EAC, for International Federation of Gynecology and Obstetrics stages I to III. METHODS: The National Cancer Data Base was queried for patients diagnosed with International Federation of Gynecology and Obstetrics (1988 classification) Stage I-III UPSC, CC, and EAC from 1998 to 2012 who underwent surgery as definitive treatment. Patients with unknown grade/stage, nonsurgical primary therapy, other histologies, and less than 30-day follow-up were excluded. Overall survival was calculated using the Kaplan-Meier product-limit method and compared using log-rank tests. RESULTS: 219,934 patients met our inclusion criteria. For patients with stage I disease (n = 174,361), 5-year OS was for 92.4% for G1EAC, 87.8% for G2EAC, 77.5% for G3EAC, 74.9% for CC, and 74.6% for UPSC. For stage II patients (n = 17,361), 5-year OS was 86.7% for G1EAC, 80.2% for G2EAC, 62.7% for G3EAC, 64.3% for CC, and 56.7% for UPSC. For stage III patients (n = 28,212), 5-year OS was 79.7% for G1EAC, 68.9% for G2EAC, 49.6% for G3EAC, 40.2% for CC, and 35.7% for UPSC (P <0.0001). On multivariate analysis, black race, age 60 years and older, higher stage, higher grade, high-risk histologies, receiving chemotherapy, and higher comorbidity scores were all significantly (P < 0.0001) predictive of death while receiving radiation therapy was protective (hazards ratio, 0.7; 95% confidence interval, 2.6-2.9). CONCLUSIONS: The results suggest that G3 EAC has a slightly more favorable survival than UPSC and CC but predictably does poorer than G1-2 EAC. Further research is warranted to determine if G3 EAC should be reclassified as a type II cancer.

Effect of a high strength chemical industry wastewater on microbial community dynamics and mesophilic methane generation.

A high strength chemical industry wastewater was assessed for its impact on anaerobic microbial community dynamics and consequently mesophilic methane generation. Cumulative methane production was 251 mL/g total chemical oxygen demand removed at standard temperature and pressure at the end of 30 days experimental period with a highest recorded methane percentage of 80.6% of total biogas volume. Volatile fatty acids (VFAs) analysis revealed that acetic acid was the major intermediate VFAs produced with propionic acid accumulating over the experimental period. Quantitative analysis of microbial communities in the test and control groups with quantitative real time polymerase chain reaction highlighted that in the test group, Eubacteria (96.3%) was dominant in comparison with methanogens (3.7%). The latter were dominated by Methanomicrobiales and Methanobacteriales while Methanosarcinaceae in test groups increased over the experimental period, reaching a maximum on day 30. Denaturing gradient gel electrophoresis profile was performed, targeting the 16S rRNA gene of Eubacteria and Archaea, with the DNA samples extracted at 3 different time points from the test groups. A phylogenetic tree was constructed for the sequences using the neighborhood joining method. The analysis revealed that the presence of organisms resembling Syntrophomonadaceae could have contributed to increased production of acetic and propionic acid intermediates while decrease of organisms resembling Pelotomaculum sp. could have most likely contributed to accumulation of propionic acid. This study suggested that the degradation of organic components within the high strength industrial wastewater is closely linked with the activity of certain niche microbial communities within eubacteria and methanogens.

Effects of diet and antibiotics on anastomotic healing: A mouse model study with varied dietary fiber and fat, and pre-operative antibiotics.

INTRODUCTION: This study investigated the separate impacts of diet and pre-operative antibiotics on gut microbiome and colonic anastomotic healing using a mouse model. METHODS: Male C57BL/6J mice were fed either low-fat-high-fibre (SD) or high-fat-low-fiber (WD) groups for 6 weeks, then further received either pre-operative antibiotics or a control sham before a colonic anastomotic procedure was performed. After 7 days, the anastomosis was assessed and microbiota composition and biodiversity were analyzed in anastomotic tissue and stool. RESULTS: WD-fed mice had shorter survival (5.2 â€‹± â€‹2.3 vs. 6.9 â€‹± â€‹2.3 days, p â€‹= â€‹0.022), increased weight loss (5.55 â€‹± â€‹3.80g vs. 2.65 â€‹± â€‹2.36g, p â€‹= â€‹0.03), and reduced biodiversity compared to SD-fed mice. Pre-operative antibiotics improved anastomotic healing scores (1.33 â€‹± â€‹0.65 vs. 2.08 â€‹± â€‹0.79, p â€‹= â€‹0.02) and reduced Enterococcus faecalis growth in tissue and stool (p â€‹= â€‹0.02, p â€‹= â€‹0.02). Improved anastomotic healing correlated with lower Enterococcus abundance (p â€‹= â€‹0.04) and higher collagen III and IV levels (p â€‹= â€‹0.01, 0.04) in anastomotic tissue. CONCLUSION: SD promotes enhanced post-operative recovery and increased microbiome biodiversity, while pre-operative antibiotics enhance anastomotic healing by suppressing Enterococcus faecalis growth, mitigating collagen III/IV degradation.

Head and Neck Cancer Patient Population, Management, and Oncologic Outcomes from the COVID-19 Pandemic.

The COVID-19 pandemic precipitated drastic changes in cancer care. Its impact on the U.S. head and neck cancer population has yet to be fully understood. This study aims to understand the impact of pandemic-related changes on the head and neck cancer population. An observational study of head and neck cancer patients at a single institution during the spring of 2020 and 2019 was performed. Clinical characteristics and survival outcomes were analyzed. In 2020, 54 head and neck cancer patients were evaluated in the department of radiation oncology vs. 74 patients seen in 2019; 42% of the patients were female in 2019 versus 24% in 2020 (p = 0.036). The median follow-up time was 19.4 and 31 months for 2020 and 2019, respectively. After adjusting for stage, the relapse-free survival probability at 6 and 12 months was 79% and 69% in 2020 vs. 96% and 89% in 2019, respectively (p = 0.036). There was no significant difference in the overall survival, with 94% and 89% in 2020 and 2019, respectively (p = 0.61). Twenty-one percent of patients received induction chemotherapy in 2020 versus 5% in 2019 (p = 0.011); significantly more treatment incompletions occurred in 2020, 9% vs. 0% in 2019 (p = 0.012). Moreover, the stage-adjusted RFS differed between cohorts, suggesting head and neck cancer patients seen during the initial wave of COVID-19 may experience worse oncologic outcomes.

Adjuvant Reirradiation With Proton Therapy in Head and Neck Squamous Cell Carcinoma.

Purpose: For patients with head and neck squamous cell carcinoma (HNSCC), locoregional failure and second primary tumors are common indications for adjuvant reirradiation (re-RT). Given an absence of clear consensus on the role of adjuvant re-RT, we sought to assess histopathologic risk factors of patients with HNSCC and their resulting outcomes after adjuvant re-RT with proton therapy. Methods and Materials: We conducted a retrospective analysis of patients with HNSCC who underwent salvage surgery at our institution followed by adjuvant re-RT with proton therapy over 1.5 years. All included patients received prior radiation therapy. The Kaplan-Meier method was used to evaluate locoregional recurrence-free survival and overall survival. Results: The cohort included 22 patients, with disease subsites, including oropharynx, oral cavity, hypopharynx, larynx, and nasopharynx. Depending on adverse pathologic features, adjuvant re-RT to 66 Gy (32% of cohort) or 60 Gy (68%), with (59%) or without (41%) concurrent systemic therapy was administered. The majority (86%) completed re-RT with no reported treatment delay; 3 patients experienced grade ≥3 acute Common Terminology Criteria for Adverse Events toxicity and no patient required enteral feeding tube placement during re-RT. Median follow-up was 21.0 months (IQR, 11.7-25.2 months). Five patients had biopsy-proven disease recurrences a median of 5.9 months (IQR, 3.8-9.7 months) after re-RT. Locoregional recurrence-free survival was 95.2%, 70.2%, 64.8% at 6, 12, and 24 months, respectively. OS was 100%, 79.2%, and 79.2% at 6, 12, and 24 months, respectively. Four patients had osteoradionecrosis on imaging a median of 13.2 months (IQR, 8.7-17.4 months) after re-RT, with 2 requiring surgical intervention. Conclusions: Adjuvant re-RT for patients with HNSCC was well-tolerated and offered reasonable local control in this high-risk cohort but appears to be associated with a risk of osteoradionecrosis. Additional study and longer follow-up could help define optimal patient management in this patient population.

The relative importance of hormonal therapy and biological effective dose in optimizing prostate brachytherapy treatment outcomes.

OBJECTIVES: To compare the relative importance of radiation dose escalation vs androgen deprivation therapy (ADT) in the definitive treatment of prostate adenocarcinoma. PATIENTS AND METHODS: In total, 2427 patients with prostate adenocarcinoma were treated with definitive brachytherapy or brachytherapy with external beam radiation with or without ADT. Over the 20-year period of the present study (median follow-up of 78 months), patients were treated with a range of doses that were converted to the biological effective dose (BED) and/or ADT as the treatment paradigms were optimized. Using univariate and multivariate analysis, the relative impact on the biochemical control and post-treatment prostate biopsy results of BED vs ADT was determined. RESULTS: The 10-year freedom from biochemical failure (FBF) was significantly affected by BED group: ≤150 Gy2 (64%), >150-200 Gy2 (88%), >200-220 Gy2 (89%) and >220 Gy2 (89.5%) (P < 0.001). When stratified into dose groups, ADT improved FPF on multivariate analysis for the BED group (<150 Gy2 , hazard ratio = 0.55; >150-200 Gy2 , hazard ratio = 0.39) but not for the higher BED groups. Among patients receiving ADT, a significant difference in 10-year FBF was seen when stratifying BED into groups ≤150 Gy2 (78%) vs >150 Gy2 (87%) (P = 0.01). On logistic regression, ADT had a significant impact on obtaining a negative biopsy (hazard ratio = 0.21) with BED <200 Gy2 , although there was no difference with BED >200 Gy2 . CONCLUSIONS: When treated with brachytherapy with or without EBT, ADT improves FBF only in the setting of lower doses. The benefit of ADT may be primarily as an enhancer of local control, explaining why high radiation doses can compensate for its absence.

A Trace Mineral Injection before Joining and Lambing Increases Marking Percentages and Lamb Weights on Diverse Farms in Victoria, Australia.

This study was conducted on five commercial farms across Victoria, Australia, between September 2018 and November 2019, where the TM status of ewes was within normal ranges before joining. Mix breed ewes (n = 1484) were randomly allocated to receive either nil treatment (Control) or two injections of an ITM product containing zinc (40 mg/mL), manganese (10 mg/mL), selenium (3 mg/mL), and copper (10 mg/mL); 0.2 mL per 10 kg BW (Multimin® plus Copper for Sheep, Virbac (Australia) Pty Ltd., Milperra, NSW, Australia) 30 days before the start of joining and 30 days before the start of lambing. Approximately 90 days after joining, pregnancy status and conception rate were determined by ultrasound. The marking rate was determined approximately four weeks after the end of lambing, and lamb weights were determined at weaning (12 weeks after the end of lambing). In all farms, ITM treatment did not affect the conception rate. The average conception rate was 156 ± 11.0% (p > 0.05). The marking rate of ITM ewes was 9% higher than control ewes (95% Confidence Interval 3−21%). Lambs born to ITM ewes were 2.31 kg heavier at weaning than lambs born to control ewes (p < 0.001). Although not significant, ewe mortality across farms was 1.3% lower in the ITM group than in the control group. On average, ewes treated with ITM pre-joining and pre-lambing produced more and heavier lambs that represent an extra AU$ 2338 per 100 ewes net benefit for the producer. These results help to understand strategic TM supplementation for animal health, performance and farm profitability beyond the treatment of clinical deficiencies.

High Failure Rates in Young Nonsmoker Nondrinkers With Squamous Cell Carcinoma of the Oral Tongue.

OBJECTIVE(S): 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. METHODS: 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 (age >45). Outcome analysis was performed using Kaplan Meier method. Multivariable Cox proportional hazard models were performed for age and stage. RESULTS: 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 (age >45), 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). CONCLUSIONS: 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. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1110-1121, 2023.

Tumor-wide RNA splicing aberrations generate immunogenic public neoantigens.

T-cell-mediated immunotherapies are limited by the extent to which cancer-specific antigens are homogenously expressed throughout a tumor. We reasoned that recurrent splicing aberrations in cancer represent a potential source of tumor-wide and public neoantigens, and to test this possibility, we developed a novel pipeline for identifying neojunctions expressed uniformly within a tumor across diverse cancer types. Our analyses revealed multiple neojunctions that recur across patients and either exhibited intratumor heterogeneity or, in some cases, were tumor-wide. We identified CD8+ T-cell clones specific for neoantigens derived from tumor-wide and conserved neojunctions in GNAS and RPL22 , respectively. TCR-engineered CD8 + T-cells targeting these mutations conferred neoantigen-specific tumor cell eradication. Furthermore, we revealed that cancer-specific dysregulation in splicing factor expression leads to recurrent neojunction expression. Together, these data reveal that a subset of neojunctions are both intratumorally conserved and public, providing the molecular basis for novel T-cell-based immunotherapies that address intratumoral heterogeneity.

Vitamin D content of food and its contribution to vitamin D status: a brief overview and Australian focus.

There are only a few natural foods that contain nutritionally significant quantities of vitamin D. These include egg yolk, some fatty fish, and in much lower concentrations, meat. The published values of the vitamin D content of food are summarised here and their contribution to dietary vitamin D intake is discussed, with particular reference to Australia. Dietary vitamin D is unlikely to reach the level recommended by the US Institute of Medicine. It is therefore concluded that dietary vitamin D will only be a component of vitamin D supply, with UV exposure and/or oral supplements continuing to be the main sources of vitamin D to maintain adequate status.

Direct SARS-CoV-2 Detection System Utilizing Simple-to-Use Capillary Gel Electrophoresis Sample-to-Result.

We present a Direct SARS-CoV-2 Detection System that achieves sample-to-results in less than two hours in three simple steps. The Detection System includes Direct one-step Reverse Transcription PCR (RT-PCR) reagents (Qexp-MDx kit), a portable thermal cycler (Qamp-mini) with a pre-programmed chip and a simple-to-use Capillary Gel Electrophoresis system &amp;#40;Qsep Series Bio-Fragment Analyzer&amp;#41; with high fluorescence detection sensitivity to solve the problems associated with traditional real-time PCR (qPCR) systems which produces inaccurate test results with high false negative and false positive rates. The proposed simple-to-use detection platform can provide high detection sensitivity (identify less than 20 copies), fast results (less than 120 minutes) and cost-effective results which should be suitable for decentralized testing application of COVID-19.

Management of Older Adults with Locally Advanced Head and Neck Cancer.

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.

Functional Larynx Preservation in Patients With Locally Advanced Squamous Cell Carcinoma of the Larynx and Hypopharynx Treated With Induction Chemotherapy vs. Concurrent Chemoradiation Alone.

Objectives Chemoradiation therapy (CRT) has been established as a standard treatment for locally advanced hypopharynx/larynx squamous cell carcinoma (SCC) but the role of induction chemotherapy (IC) remains unclear. The primary outcome of this study is to determine whether functional larynx-preservation survival (FLPS) is improved with the addition of IC in these patients. Secondary outcomes were overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and laryngectomy rates. Methods Records for patients with AJCC 8th edition clinical stage III-IVB laryngeal and hypopharyngeal SCC treated with CRT +/- IC from 2005-2019 were reviewed. FLPS was defined as time until death, progression, laryngectomy, or non-functional larynx. Kaplan-Meier curves were generated for FLPS, OS, PFS, and DMFS. Outcomes were compared using the stratified log-rank test. Laryngectomy rates were compared using Fisher's exact test. Results We included 52 patients with laryngeal and 38 with hypopharyngeal SCC (n=90); 19 patients with laryngeal SCC and 19 with hypopharyngeal SCC received IC (median three cycles). There were no differences in the three-year FLPS (61% vs 67.8%; p=0.88), OS (73.9% vs 86.2%; p=0.42), PFS (53.6% vs 62.6%; p=0.44), or DMFS (65.2% vs 71.5%, p= 0.85) between patients who did and did not receive IC all patients. Laryngectomy rates did not differ with and without IC (18.4 % vs 7.7%; p=0.19). Conclusion In this study of advanced laryngeal and hypopharyngeal SCC, IC did not improve three-year FLPS, OS, PFS, or laryngectomy rates compared to CRT alone. A large prospective series would provide a more robust understanding of the role of IC in this group of patients.

Treatment tolerability and outcomes in elderly patients with head and neck cancer.

PURPOSE: The number of elderly patients with head and neck squamous cell carcinoma (HNSCC) continues to grow. Management of this cohort remains poorly defined. We investigated treatment tolerability and clinical outcomes in this underrepresented population. METHODS: We identified patients aged ≥70 with nonrecurrent, nonmetastatic HNSCC treated curatively from 2007-2018 and analyzed clinical covariates. RESULTS: Two hundred and twenty patients with a median age of 75 (interquartile range:72-80) were identified. Age and comorbidities were not correlated with toxicity (P ≥ .05). Patients who experienced a treatment interruption had significantly greater weight loss (P = .042) and worse overall survival (OS) (P < .001), but not worse disease-specific survival (P = .45), or locoregional control (P = .21). CONCLUSIONS: Treatment interruptions were associated with weight loss and worse OS, but not disease related outcomes, suggesting an interruption in the elderly may be a surrogate for another issue. In sum, our data should guide clinical trial design to benefit this growing, neglected cohort.