The Effect of Protective Headgear on Concussion Injury Ratesin High School Girls' Lacrosse

Background: The use of headgear is a controversial issue in girls' lacrosse with competing arguments pitting the potential benefits of protective headgear versus the potential for increased aggression and related injury due to risk compensation. However, there is scant field-based evidence regarding the effectiveness of protective headgear for reducing the risk of concussion among girls' lacrosse players to support either argument. Furthermore, there is a recognized difference in lacrosse game play geographically with some regions having mature and others still developing girls' lacrosse traditions. Therefore, we aimed to (i) compare concussion rates among high school lacrosse players with headgear versus without headgear;and (ii) compare concussion rates among players with headgear versus without headgear among states with “emerging” lacrosse play. Methods: Study participants included high school girls' lacrosse players from across the country during the Spring 2019 season, the initial part of the 2020 season (prior to the COVID-19 shutdown), and through the middle of the 2021 season. A convenience sample of high schools with athletic trainers were recruited to report injury and athlete exposure (AE) data for girls' lacrosse to the High School National Athletic Treatment, Injury and Outcomes Network (NATION) injury surveillance system. Comparisons were made between concussion rates in the state of Florida (a state with emerging game play that mandates the use of headgear during high school girls' lacrosse participation) to (i) all states without a headgear use mandate, and (ii) emerging states without a headgear use mandate. Emerging states were categorized a-priori by an expert panel as states other than CT, DC, DE, MA, MD, ME, NC, NH, NJ, NY, PA, RI, VA, and VT. Incidence Rate Ratios (IRR) and 95% Confidence Intervals (CI) were calculated. IRRs with corresponding CIs that excluded 1.000 were deemed statistically significant. Results: A total of 84 concussions (Headgear: 20;Non-Headgear: 64) and 239,693AE were reported (Headgear: 78,464AE;Non-Headgear: 161,229AE) across all games and practices. Concussion incident rates per 1000 AE were (Headgear: 0.255;and Non-Headgear: 0.397;IRR = 1.557, 95% CI: 0.943 - 2.573). Comparing incident rates for Headgear to the Emerging Non-Headgear states (61,197 AE;0.458 concussions per 1000 AE) yielded an IRR of1.795 (95% CI: 1.011, 3.186). Conclusion: These interim findings indicate that concussion rates among high school girls' lacrosse players not wearing headgear were 56% higher than those wearing headgear in the state of Florida, although these results did not reach statistical significance. In comparison with other emerging states where the level of lacrosse play is similar, players not wearing headgear experienced a 79.5% higher rate of concussion (statistically significant). Final results will include data from the remainder of the 2021 season.

Plasma Oxylipins and Their Precursors Are Strongly Associated with COVID-19 Severity and with Immune Response Markers.

COVID-19 is characterised by a dysregulated immune response, that involves signalling lipids acting as mediators of the inflammatory process along the innate and adaptive phases. To promote understanding of the disease biochemistry and provide targets for intervention, we applied a range of LC-MS platforms to analyse over 100 plasma samples from patients with varying COVID-19 severity and with detailed clinical information on inflammatory responses (>30 immune markers). The second publication in a series reports the results of quantitative LC-MS/MS profiling of 63 small lipids including oxylipins, free fatty acids, and endocannabinoids. Compared to samples taken from ward patients, intensive care unit (ICU) patients had 2-4-fold lower levels of arachidonic acid (AA) and its cyclooxygenase-derived prostanoids, as well as lipoxygenase derivatives, exhibiting negative correlations with inflammation markers. The same derivatives showed 2-5-fold increases in recovering ward patients, in paired comparison to early hospitalisation. In contrast, ICU patients showed elevated levels of oxylipins derived from poly-unsaturated fatty acids (PUFA) by non-enzymatic peroxidation or activity of soluble epoxide hydrolase (sEH), and these oxylipins positively correlated with markers of macrophage activation. The deficiency in AA enzymatic products and the lack of elevated intermediates of pro-resolving mediating lipids may result from the preference of alternative metabolic conversions rather than diminished stores of PUFA precursors. Supporting this, ICU patients showed 2-to-11-fold higher levels of linoleic acid (LA) and the corresponding fatty acyl glycerols of AA and LA, all strongly correlated with multiple markers of excessive immune response. Our results suggest that the altered oxylipin metabolism disrupts the expected shift from innate immune response to resolution of inflammation.

Severe COVID-19 Is Characterised by Perturbations in Plasma Amines Correlated with Immune Response Markers, and Linked to Inflammation and Oxidative Stress.

The COVID-19 pandemic raised a need to characterise the biochemical response to SARS-CoV-2 infection and find biological markers to identify therapeutic targets. In support of these aims, we applied a range of LC-MS platforms to analyse over 100 plasma samples from patients with varying COVID-19 severity and with detailed clinical information on inflammatory responses (>30 immune markers). The first publication in a series reports the results of quantitative LC-MS/MS profiling of 56 amino acids and derivatives. A comparison between samples taken from ICU and ward patients revealed a notable increase in ten post-translationally modified amino acids that correlated with markers indicative of an excessive immune response: TNF-alpha, neutrophils, markers for macrophage, and leukocyte activation. Severe patients also had increased kynurenine, positively correlated with CRP and cytokines that induce its production. ICU and ward patients with high IL-6 showed decreased levels of 22 immune-supporting and anti-oxidative amino acids and derivatives (e.g., glutathione, GABA). These negatively correlated with CRP and IL-6 and positively correlated with markers indicative of adaptive immune activation. Including corresponding alterations in convalescing ward patients, the overall metabolic picture of severe COVID-19 reflected enhanced metabolic demands to maintain cell proliferation and redox balance, alongside increased inflammation and oxidative stress.

The digital design build: Modes of experiential learning in the pandemic era

In recent years, academia has deviated from the lecture-based model to a hybridized system of instruction and experiential learning. Experiential learning aids students in understanding collaborative processes in architectural praxis and exposes them to engaging learning opportunities, a critical component of architectural studio education (Nijholt et al. 2013). During the COVID-19 outbreak, students are barred from accessing on-campus facilities. This causes a redevelopment of curricular delivery and disrupts experiential learning which heavily relies on in-person interaction. It is imperative for instructors to retain experiential learning in the transition to virtual instruction. This paper explores experiential learning within virtual platforms for instruction. Through outlining the implementation of technologies, capitalizing on connectivity, and maximizing opportunity for digital problem solving, the authors posit a framework that other educators may adopt. The paper concludes with a case study of a virtual design-build project, and the various techniques implemented in retaining experiential learning during the pandemic. © 2021 and published by the Association for Computer-Aided Architectural Design Research in Asia (CAADRIA), Hong Kong.

TRB sequences targeting ORF1a/b are associated with disease severity in hospitalized COVID-19 patients.

The potential protective or pathogenic role of the adaptive immune response to SARS-CoV-2 infection has been vigorously debated. While COVID-19 patients consistently generate a T lymphocyte response to SARS-CoV-2 antigens, evidence of significant immune dysregulation in these patients continues to accumulate. In this study, next generation sequencing of the T cell receptor beta chain (TRB) repertoire was conducted in hospitalized COVID-19 patients to determine if immunogenetic differences of the TRB repertoire contribute to disease course severity. Clustering of highly similar TRB CDR3 amino acid sequences across COVID-19 patients yielded 781 shared TRB sequences. The TRB sequences were then filtered for known associations with common diseases such as EBV and CMV. The remaining sequences were cross-referenced to a publicly accessible dataset that mapped COVID-19 specific TCRs to the SARS-CoV-2 genome. We identified 158 SARS-CoV-2 specific TRB sequences belonging to 134 clusters in our COVID-19 patients. Next, we investigated 113 SARS-CoV-2 specific clusters binding only one peptide target in relation to disease course. Distinct skewing of SARS-CoV-2 specific TRB sequences toward the nonstructural proteins (NSPs) encoded within ORF1a/b of the SARS-CoV-2 genome was observed in clusters associated with critical disease course when compared to COVID-19 clusters associated with a severe disease course. These data imply that T-lymphocyte reactivity towards peptides from NSPs of SARS-CoV-2 may not constitute an effective adaptive immune response and thus may negatively affect disease severity.

Extensive longitudinal immune profiling reveals sustained innate immune activation in COVID-19 patients with unfavorable outcome

COVID-19 differs substantially between individuals, ranging from mild to severe or even fatal. Heterogeneity in the immune response against SARS-COV-2 likely contributes to this. Therefore, we explored the temporal dynamics of key cellular and soluble mediators of innate and adaptive immune activation in relation to COVID-19 severity and progression. Forty-four patients with a PCR-proven diagnosis of COVID-19 were included. Extensive cellular (leukocytes and T-lymphocyte subsets) and serological immune profiling (cytokines, soluble cell surface molecules, and SARS-CoV-2 antibodies) was performed at hospital admission and every 3-4 days during hospitalization. Measurements and disease outcome were compared between patients with an unfavorable (IC admission and/or death) and favorable (all others) outcome. Patients with an unfavorable outcome had higher leukocyte numbers at baseline, mostly due to increased neutrophils, whereas lymphocyte and monocyte numbers were reduced. CRP, IL-6, CCL2, CXCL10, and GM-CSF levels were higher at baseline in the unfavorable group, whereas IL-7 levels were lower. SARS-CoV-2 antibodies were more frequently absent in the unfavorable group. Longitudinal analysis revealed delayed kinetics of activated CD4 and CD8 T-lymphocyte subsets in the unfavorable group. Furthermore, whereas CRP, IL-6, CXCL10, and GM-CSF declined in the favorable group, these cytokines declined with delayed kinetics, remained increased, or even increased further in the unfavorable group. Our data indicate a state of increased innate immune activation in COVID19-patients with an unfavorable outcome at hospital admission, which remained over time, as compared with patients with a favorable outcome.

Fever range whole body hyperthermia for re-irradiation of head and neck squamous cell carcinomas: Final results of a prospective study.

OBJECTIVES: Fever-range whole body hyperthermia (FRWBH) has been shown to improve tumor oxygenation in vivo. A prospective pilot study addressed the question if addition of FRWBH to re-irradiation is feasible in recurrent head and neck squamous cell carcinomas (HNSCC) with unfavorable prognostic features. MATERIALS AND METHODS: The study completed accrual with the recruitment of ten patients between April 2018 and March 2020. Re-irradiation was administered using volumetric arc hyperfractionated radiotherapy with bi-daily 1.2 Gray (Gy) single fractions and a total dose of 66 Gy to all macroscopic tumor lesions. Concomitant chemotherapy consisted mostly of cisplatin (7 patients). FRWBH was scheduled weekly during re-irradiation. The study was registered in the clinicaltrials.gov database (NCT03547388). RESULTS: Only five patients received all cycles of FRWBH. Poor patient compliance, active infections during treatment and study restrictions due to the Covid-19 pandemic were the main reasons for omitting FRWBH. No increase of acute toxicity was observed by FRWBH. Exploratory evaluation of outcome data suggests that FRWBH treatment according to protocol does not seem to have a detrimental effect on tumor control or survival and might even increase treatment efficacy. CONCLUSION: FRWBH is difficult to apply concomitant to re-irradiation in HNSCC. No excess toxicity was observed in patients receiving FRWBH and exploratory analyses suggest potential anti-tumor activity and decreased patient-reported depression scores after FRWBH.

Outcome of older cancer patientsinfected with Covid19 at Gustave Roussy Cancer Center

Background: The SARS-CoV-2 outbreak in Paris's region significantly affected Gustave Roussy Cancer Center.Previous analyses showed that mortality rate increases with age in the general population. Here, we report theGustave Roussy experience on older patients (OP) with cancer during the SARS-CoV-2 outbreak. Methods: Cancer pts with suspected SARS-CoV-2 infection were admitted at Gustave Roussy starting March 12th.Screening indications have been adapted over the time. All the COVID19 pts positively tested and managed atGustave Roussy between March 14th (1st positive case) and April 15th have been included in a REDCap database.Pts and underlying oncologic and COVID19 diseases characteristics have been collected. Cancer and COVID-19managements and outcomes have been assessed. The primary endpoint of this analysis was the clinicaldeterioration, defined as the need for O2 supplementation of 6l/min, or death of any cause. Results: Among the first 137 cancer pts diagnosed with SARS-CoV-2, 36 patients were aged 70 years (26%). Mostof them were female (61%) with a median age of 75.5 years old. Most frequent underlying cancers were solidtumors (92%) including GI (19%), lung (17%), GYN (14%), and head and neck (14%). Most OP (36%) were ECOGperformance status 2 versus 24% in younger patients (YP). The diagnosis of SARS-CoV-2 infection was made byRT-PCR or thoracic CT scan alone in 97% and 3% of the cases, respectively, in OP and in 92% and 8% in YP. MostOP experienced symptoms prior to testing (92%) compared to YP (80%). Symptoms differed according to age withmore cough with sputum production in OP (14% versus 5%), dyspnea (39% versus 31%), diarrhea (17% versus9%), shivers (8% versus 0%), sore throat (8% versus 4%), and no anosmia or agueusia. The majority of OP werehospitalized (81%) compared to 72% of YP and treated with HCQ/AZI (15;52%) with inclusion in the ONCOVID trial(EudraCT: 2020-01250-21) compared to 25 (35%) YP. They did not receive any IL-6 inhibitor. Only one OP wasadmitted in the ICU (3%). Clinical deterioration occurred in 10 OP (29%). There was no impact of age on clinicalworsening (HR=1.157;95%CI 0.55-2.42;p=0.7). However, age was associated with worse overall survival (OS)(HR=2.45 95%CI 1.02-5.92 ;p=0.0463). Results will be updated at the meeting. Conclusions: OP with cancer had a different disease presentation, same rate of clinical worsening, but worse OSin SARS-CoV-2 infection.