Key benefits of dexamethasone and antibody treatment in COVID-19 hamster models revealed by single-cell transcriptomics

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HBV患者血清YKL-40、CA19-9、GP73水平与其病情相关性

目的 分析HBV患者YKL-40、CA19-9、GP73水平差异及与患者病情轻重程度的相关性,探讨HBV患者病情的判定指标。方法 选取2015年5月—2018年5月收治的100例HBV患者,其中慢性HBV感染组40例、慢性乙型肝炎组36例、HBV相关肝硬化组24例,同期选择我院健康体检的健康者50例作为健康对照组;检测患者血中YKL-40、CA19-9、GP73水平;分析HBV感染患者血清YKL-40、CA19-9、GP73水平与病情轻重程度的相关性。结果 慢性HBV感染、慢性乙型肝炎及HBV相关肝硬化患者血中YKL-40水平分别为（36.38±4.19）ng/mL 、（49.02±4.32）ng/mL、（65.14±5.21）ng/mL ,CA19-9分别为（12.03±1.03）KU/L、（13.84±0.98）KU/L、（16.94±0.81）KU/L,GP73分别为（47.22±5.38）ng/mL 、（98.53±10.24）ng/mL 、（229.85±12.19）ng/mL,均明显高于对照组的（28.19±3.27）ng/mL 、（7.34±0.92）KU/L 、（30.93±3.89）ng/mL,均P=0.000 0。随着慢性HBV感染者、慢性乙型肝炎患者和不同HBV相关肝硬化患者肝脏炎症及纤维化程度加重,患者血中YKL-40、CA19-9和GP73也随之显著增加,均P=0.000 0;YKL-40、CA19-9和GP73均是影响HBV感染患者体内炎症坏死及肝脏纤维化的独立性影响因素,差异有统计学意义（P<0.05）。结论 HBV感染患者血清中YKL-40、CA19-9、GP73水平是HBV感染患者病情轻重程度的独立性影响因素。     

A prime-boost concept using a T-cell epitope-driven DNA vaccine followed by a whole virus vaccine effectively protected pigs in the pandemic H1N1 pig challenge model

Influenza A virus (IAV) vaccines in pigs generally provide homosubtypic protection but fail to prevent heterologous infections. In this pilot study, the efficacy of an intradermal pDNA vaccine composed of conserved SLA class I and class II T cell epitopes (EPITOPE) against a homosubtypic challenge was compared to an intramuscular commercial inactivated whole virus vaccine (INACT) and a heterologous prime boost approach using both vaccines. Thirty-nine IAV-free, 3-week-old pigs were randomly assigned to one of five groups including NEG-CONTROL (unvaccinated, sham-challenged), INACT-INACT-IAV (vaccinated with FluSure XP® at 4 and 7 weeks, pH1N1 challenged), EPITOPE-INACT-IAV (vaccinated with PigMatrix EDV at 4 and FluSure XP® at 7 weeks, pH1N1 challenged), EPITOPE-EPITOPE-IAV (vaccinated with PigMatrix EDV at 4 and 7 weeks, pH1N1 challenged), and a POS-CONTROL group (unvaccinated, pH1N1 challenged). The challenge was done at 9 weeks of age and pigs were necropsied at day post challenge (dpc) 5. At the time of challenge, all INACT-INACT-IAV pigs, and by dpc 5 all EPITOPE-INACT-IAV pigs were IAV seropositive. IFNγ secreting cells, recognizing vaccine epitope-specific peptides and pH1N1 challenge virus were highest in the EPITOPE-INACT-IAV pigs at challenge. Macroscopic lung lesion scores were reduced in all EPITOPE-INACT-IAV pigs while INACT-INACT-IAV pigs exhibited a bimodal distribution of low and high scores akin to naïve challenged animals. No IAV antigen in lung tissues was detected at necropsy in the EPITOPE-INACT-IAV group, which was similar to naïve unchallenged pigs and different from all other challenged groups. Results suggest that the heterologous prime boost approach using an epitope-driven DNA vaccine followed by an inactivated vaccine was effective against a homosubtypic challenge, and further exploration of this vaccine approach as a practical control measure against heterosubtypic IAV infections is warranted.     

Changes in the Management of Patients having Radical Radiotherapy for Lung Cancer during the First Wave of the COVID-19 Pandemic in the UK

AimsIn response to the COVID-19 pandemic, guidelines on reduced fractionation for patients treated with curative-intent radiotherapy were published, aimed at reducing the number of hospital attendances and potential exposure of vulnerable patients to minimise the risk of COVID-19 infection. We describe the changes that took place in the management of patients with stage I–III lung cancer from April to October 2020.Materials and methodsLung Radiotherapy during the COVID-19 Pandemic (COVID-RT Lung) is a prospective multicentre UK cohort study. The inclusion criteria were: patients with stage I–III lung cancer referred for and/or treated with radical radiotherapy between 2nd April and 2nd October 2020. Patients who had had a change in their management and those who continued with standard management were included. Data on demographics, COVID-19 diagnosis, diagnostic work-up, radiotherapy and systemic treatment were collected and reported as counts and percentages. Patient characteristics associated with a change in treatment were analysed using multivariable binary logistic regression.ResultsIn total, 1553 patients were included (median age 72 years, 49% female); 93 (12%) had a change to their diagnostic investigation and 528 (34%) had a change to their treatment from their centre's standard of care as a result of the COVID-19 pandemic. Age ≥70 years, male gender and stage III disease were associated with a change in treatment on multivariable analysis. Patients who had their treatment changed had a median of 15 fractions of radiotherapy compared with a median of 20 fractions in those who did not have their treatment changed. Low rates of COVID-19 infection were seen during or after radiotherapy, with only 21 patients (1.4%) developing the disease.ConclusionsThe COVID-19 pandemic resulted in changes to patient treatment in line with national recommendations. The main change was an increase in hypofractionation. Further work is ongoing to analyse the impact of these changes on patient outcomes.     

The magnitude and timing of recalled immunity after breakthrough infection is shaped by SARS-CoV-2 variants

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Encouraging COVID-19 vaccination via an evolutionary theoretical approach: A randomized controlled study in Japan

ObjectiveWe aimed to examine the effect of a message that target the fundamental human motive of kin care on COVID-19 vaccination recommendations among participants with young children, based on an evolutionary theoretical approach.MethodsParticipants with young children (n = 969) were randomly assigned either to a group that received an intervention message that targeted the fundamental motive of kin care, or that targeted the fundamental motive of disease avoidance, or a control message. Intention to receive COVID-19 vaccination was assessed both before and after reading the messages. A one-way ANOVA with Tukey’s or Games–Howell test was conducted.ResultsAn intervention message targeting the fundamental motive of kin care and disease avoidance significantly increased intention of vaccination versus a control message (p < 0.001, respectively).ConclusionThe evolutionary theoretical approach that focuses on fundamental human motives has the potential to extend the communication strategy for COVID-19 vaccination recommendations.Practice implicationsHealth professionals should deliver messages that target the fundamental motive of kin care as well as messages about the susceptibility and severity of COVID-19 and vaccine efficacy (e.g., “Get vaccinated against COVID-19 for your child’s sake, because if you are infected, you will be unable to care for your child.”)     

The effect of patient ethnicity on the accuracy of peripheral pulse oximetry in patients with COVID-19 pneumonitis: a single-centre,retrospective analysis

Pulse oximetry is used widely to titrate oxygen therapy and for triage in patients who are critically ill. However, there are concerns regarding the accuracy of pulse oximetry in patients with COVID-19 pneumonitis and in patients who have a greater degree of skin pigmentation. We aimed to determine the impact of patient ethnicity on the accuracy of peripheral pulse oximetry in patients who were critically ill with COVID-19 pneumonitis by conducting a retrospective observational study comparing paired measurements of arterial oxygen saturation measured by co-oximetry on arterial blood gas analysis (SaO₂) and the corresponding peripheral oxygenation saturation measured by pulse oximetry (S_pO₂). Bias was calculated as the mean difference between SaO₂ and S_pO₂ measurements and limits of agreement were calculated as bias ±1.96 SD. Data from 194 patients (135 White ethnic origin, 34 Asian ethnic origin, 19 Black ethnic origin and 6 other ethnic origin) were analysed consisting of 6216 paired SaO₂ and S_pO₂ measurements. Bias (limits of agreement) between SaO₂ and S_pO₂ measurements was 0.05% (−2.21–2.30). Patient ethnicity did not alter this to a clinically significant degree: 0.28% (1.79–2.35), −0.33% (−2.47–2.35) and −0.75% (−3.47–1.97) for patients of White, Asian and Black ethnic origin, respectively. In patients with COVID-19 pneumonitis, S_pO₂ measurements showed a level of agreement with SaO₂ values that was in line with previous work, and this was not affected by patient ethnicity.     

Survival and Outcomes of Newly Diagnosed Multiple Myeloma Patients Stratified by Transplant Status 2007-2018: Retrospective Analysis from the Canadian Myeloma Research Group Database

BackgroundConsiderable progress has been made in therapeutic options for multiple myeloma (MM). Understanding the current landscape of MM treatment options and associated outcomes in the real world is important in providing key insights into clinical and knowledge gaps which could be targeted for further optimization.MethodsThe Canadian Myeloma Research Group Database (CMRG-DB) is a prospectively maintained disease-specific database with >7000 patients. The objective of this study was to describe the trends in the treatment landscape and outcomes including early mortality, time to next treatment, and overall survival (OS) in each line of treatment stratified by autologous stem cell transplant (ASCT) receipt among newly-diagnosed MM patients in Canada between 2007 and 2018.ResultsA total of 5154 patients were identified among which 3030 patients (58.8%) received an upfront ASCT and 2124 (41.2%) did not. At diagnosis, the median age was 64 years and 58.6% were males. Bortezomib and lenalidomide were most frequently used (>50%) in first and second-line treatment respectively among both the ASCT and non-ASCT cohort. The median OS was 122.0 months (95% Cl 115.0-135.0 months) and 54.3 months (95% CI 50.8-58.8 months) for the ASCT and non-ASCT cohort respectively with an incremental decrease in OS in each subsequent line of treatment.ConclusionWe present the largest study to date in the Canadian landscape showing the characteristics, therapy usage, and outcomes among MM patients. This information will be critical in benchmarking current outcomes and provide key insight into areas of unmet needs and gaps for improvement of MM patients nationally.