Plasma essential fatty acid on hospital admission is a marker of COVID-19 disease severity.

It is important for allocation of resources to predict those COVID patients at high risk of dying or organ failure. Early signals to initiate cellular events of host immunity can be derived from essential fatty acid metabolites preceding the cascade of proinflammatory signals. Much research has focused on understanding later proinflammatory responses. We assessed if remodelling of plasma phospholipid content of essential fatty acids by the COVID-19 virus provides early markers for potential death and disease severity. Here we show that, at hospital admission, COVID-19 infected subjects who survive exhibit higher proportions of C20:4n-6 in plasma phospholipids concurrent with marked proinflammatory cytokine elevation in plasma compared to healthy subjects. In contrast, more than half of subjects who die of this virus exhibit very low C18:2n-6 and C20:4n-6 content in plasma phospholipids on hospital admission compared with healthy control subjects. Moreover, in these subjects who die, the low level of primary inflammatory signals indicates limited or aberrant stimulation of host immunity. We conclude that COVID-19 infection results in early fundamental remodelling of essential fatty acid metabolism. In subjects with high mortality, it appears that plasma n-6 fatty acid content is too low to stimulate cellular events of host immunity.

A Dosimetric Comparison of Primary Chemoradiation Versus Postoperative Radiation for Locally Advanced Oropharyngeal Cancer.

Introduction Advanced-stage oropharyngeal cancer can be treated with primary chemoradiation (CRT) or primary surgery with adjuvant radiotherapy, both with similar survival outcomes. Though primary CRT prescribes a higher dose, adjuvant radiation requires irradiating the surgical bed, which may increase the high dose planned target volume (PTV). We hypothesize that the integral dose to the neck and dose to critical structures will be lower with primary CRT than adjuvant radiotherapy. Methods We selected the last 18 patients who underwent surgery and adjuvant radiotherapy at one institution between July 2015 and August 2016 with American Joint Committee on Cancer (AJCC) stage III or IVA oropharyngeal squamous cell cancer. Primary CRT treatment plans were created on the patients' preoperative computed tomography (CT) scans and prescribed 70 Gy in 33 fractions, while postoperative plans were prescribed 60 Gy in 30 fractions. The radiation doses received by organs at risk for each primary CRT plan were compared to the corresponding adjuvant radiation plan. Results  Primary CRT plans had significantly smaller high dose PTV than adjuvant radiation plans (187.3 cc (95% CI 134.9-239.7) and 466.3 cc (95% CI 356.7-575.9), p<0.0001). The neck integral dose was lower in 14 of 18 plans using primary CRT, although this was not statistically significant (p=0.5375). The primary CRT plans had lower mean doses to ipsilateral (31.8 Gy (95% CI 27.5-36.0) vs 39.3 Gy (95% CI 35.4-43.1), p=0.0009)) and contralateral parotid glands (22.5 Gy (95% CI 22.1-22.8) vs 27.6 Gy (95% CI 23.4-31.8), p=0.0238) and larynx (20.7 Gy (95% CI 19.3-22.2) vs 40.2 Gy (95% CI 30.8-46.6), p<0.0001). Conclusion Primary CRT offered a decreased neck integral dose, though it was statistically insignificant. Primary CRT plans reduce mean dose to larynx and parotid glands in comparison to postoperative radiation, which may result in lower toxicities. Clinical trials comparing primary CRT and primary surgery are warranted to compare patient toxicities.