Immune resilience despite inflammatory stress promotes longevity and favorable health outcomes including resistance to infection.

Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammation in infectious diseases as well as other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics that quantify the balance between (i) CD8+ and CD4+ T-cell levels and (ii) gene expression signatures tracking longevity-associated immunocompetence and mortality-associated inflammation. Profiles of IR metrics in ~48,500 individuals collectively indicate that some persons resist degradation of IR both during aging and when challenged with varied inflammatory stressors. With this resistance, preservation of optimal IR tracked (i) a lower risk of HIV acquisition, AIDS development, symptomatic influenza infection, and recurrent skin cancer; (ii) survival during COVID-19 and sepsis; and (iii) longevity. IR degradation is potentially reversible by decreasing inflammatory stress. Overall, we show that optimal IR is a trait observed across the age spectrum, more common in females, and aligned with a specific immunocompetence-inflammation balance linked to favorable immunity-dependent health outcomes. IR metrics and mechanisms have utility both as biomarkers for measuring immune health and for improving health outcomes.

Research engagement by British early-career practitioners in nephrology: a multidisciplinary survey.

OBJECTIVES: To establish barriers and motivators underlying research engagement among early-career practitioners in nephrology across the UK, in order to guide potential interventions to enhance research involvement in renal units. DESIGN: Cross-sectional online survey employing a range of free-text, Likert scale and binomial/multiple-choice responses, distributed via mailing lists and social media. Topics covered research experience, research involvement and barriers, impact of COVID-19 and strategies to improve research engagement. Thematic analysis was used to assess free-text responses. SETTING: Renal units throughout the UK. PARTICIPANTS: Non-consultant healthcare staff self-identifying as working in nephrology were included (n=211), with responses from non-UK respondents or consultant nephrologists excluded (n=12). RESULTS: Responses were received from across the multidisciplinary team (physicians (n=83) and nurses (n=83)) and other allied health professionals (n=45). Most were aware of ongoing local research, but under half of them were actively involved. Multivariate analysis indicated employment as a physician, protected time for research activity and provision of appropriate training were associated with greater research experience and output. There was general enthusiasm to undertake research, but perceived barriers included insufficient staffing, lack of time, funding and encouragement. COVID-19 was felt to have further impacted negatively upon opportunities. Among the suggested strategies to promote engagement, mentorship and an online research resource were felt to be of most interest. CONCLUSIONS: In the first survey of this type in nephrology, we demonstrate differences across the multidisciplinary spectrum in perceived research experience and accessibility, which have been worsened by COVID-19. Our findings will guide strategies to broaden engagement in early-career practitioners and serve as a baseline to assess the impact of these interventions.

The COVID-19 Pandemic Is Associated with Reduced Survival after Pancreatic Ductal Adenocarcinoma Diagnosis: A Single-Centre Retrospective Analysis.

The COVID-19 pandemic has hugely disrupted healthcare provision, including oncology services. To evaluate the effects of the pandemic on referral routes leading to diagnosis, treatments, and prognosis in patients with pancreatic ductal adenocarcinoma, we performed a retrospective cohort study at a single tertiary centre in the UK. The patients were identified from the weekly hepatopancreatobiliary multidisciplinary team meetings between February 2018 and March 2021. The demographic, referral, and treatment data for each patient and date of death, where applicable, were extracted from the electronic patient record. The patients (n = 203) were divided into "pre-pandemic" and "pandemic" cohorts based on a referral date cut-off of 23rd March 2020. The median survival was 7.4 months [4.9-9.3] in the "pre-pandemic" cohort (n = 125), halving to 3.3 months [2.2-6.0], (p = 0.015) in the "pandemic" cohort (n = 78). There was no significant difference in patient characteristics between the two cohorts. There was a trend toward increased emergency presentations at diagnosis and reduced use of surgical resection in the "pandemic" cohort. This small-scale study suggested that the COVID-19 pandemic is associated with a halving of median survival in pancreatic ductal adenocarcinoma. Urgent further studies are required to confirm these findings and examine corresponding effects in other cancer types.